Band 8, Heft 1

Spinal muscular atrophy (SMA) is one of the leading genetic diseases of children and infants. SMA is caused by deletions or mutations of Survival Motor Neuron 1 ( SMN1 ) gene. SMN2 , a nearly identical copy of SMN1 , cannot compensate for the loss of SMN1 due to predominant skipping of exon 7. While various regulatory elements that modulate SMN2 exon 7 splicing have been proposed, intronic splicing silencer N1 (ISS-N1) has emerged as the most promising target thus far for antisense oligonucleotide-mediated splicing correction in SMA. Upon procuring exclusive license from the University of Massachussets Medical School in 2010, Ionis Pharmaceuticals (formerly ISIS Pharamaceuticals) began clinical development of Spinraza ™ (synonyms: Nusinersen, IONIS-SMN RX , ISIS-SMN RX ), an antisense drug based on ISS-N1 target. Spinraza ™ showed very promising results at all steps of the clinical development and was approved by US Food and Drug Administration (FDA) on December 23, 2016. Spinraza ™ is the first FDA-approved treatment for SMA and the first antisense drug to restore expression of a fully functional protein via splicing correction. The success of Spinraza ™ underscores the potential of intronic sequences as promising therapeutic targets and sets the stage for further improvement of antisense drugs based on advanced oligonucleotide chemistries and delivery protocols.

Fragile X syndrome (FXS) is the leading genetic cause of autism spectrum disorder (ASD) and inherited intellectual disability (ID) worldwide. Preclinical successes in understanding the biology of FXS have led to numerous translational attempts in human clinical trials of therapeutics that target the excitatory/inhibitory neural signaling imbalances thought to underlie FXS. Despite the preclinical success story, the negative results of the human clinical trials have been deemed to be at least in part disappointing by the field. In this commentary, we contend that such negative studies results in clinical trials may actually propel the FXS field forward by serving as important lessons for designing and implementing improved future clinical trials such that can objectively assess the full range of responses to new therapeutics.

Aim Status epilepticus (SE) results in the generation of reactive oxygen species (ROS), which contribute to seizure-induced brain injury. It is well known that oxidative stress plays a pivotal role in status epilepticus (SE). Thymoquinone (TQ) is a bioactive monomer extracted from black cumin (Nigella sativa) seed oil that has anti-inflammatory, anti-cancer, and antioxidant activity in various diseases. This study evaluated the protective effects of TQ on brain injury in a lithium-pilocarpine rat model of SE and investigated the underlying mechanism related to antioxidative pathway. Methods Electroencephalogram and Racine scale were used to value seizure severity. Passive-avoidance test was used to determine learning and memory function. Moreover, anti-oxidative activity of TQ was observed using Western blot and super oxide dismutase (SOD) activity assay. Results Latency to SE increased in the TQ-pretreated group compared with rats in the model group, while the total power was significantly lower. Seizure severity measured on the Racine scale was significantly lower in the TQ group compared with the model group. Results of behavioral experiments suggest that TQ may also have a protective effect on learning and memory function. Investigation of the protective mechanism of TQ showed that TQ-pretreatment significantly increased the expression of Nrf2, HO-1 proteins and SOD in the hippocampus. Conclusion These findings showed that TQ attenuated brain injury induced by SE via an anti-oxidative pathway.

Background In military men, performance such as gun-shooting precision relies on factors such as the ability to resist visual illusion, and this misperception of visual stimulus might be linked with sensation seeking related personality. Methods We have invited 103 male military men and 104 age-matched university male students to undergo the experiment of the Brentano version of the Müller-Lyer illusion and the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) tests. Results The military men scored significantly lower than students did on the ZKPQ Impulsive Sensation Seeking test but higher on Aggression-Hostility and Sociality test, and displayed less misperception magnitude to the illusion. The Impulsive Sensation Seeking, Neuroticism-Anxiety and Aggression-Hostility traits in military men, and the Activity in students were respectively correlated with the misperception magnitudes of the illusion in different manners. Conclusion Limited results in our study have indicated that the military men had pronounced personality traits which were correlated with the misperception magnitude of the Müller-Lyer illusion.

Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and activation of its signal pathway plays an important role in regulating protein growth and synthesis as well as cell proliferation and survival. In the present study, we examined the contribution of mTOR and its downstream products to brain injuries and neurological deficiencies after cardiac arrest (CA) induced-transient global ischemia. CA was induced by asphyxia followed by cardiopulmonary resuscitation (CPR) in rats. Our results showed that expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) pathways were amplified in CA rats compared to their controls. Blocking mTOR using rapamycin attenuated upregulation of pro-inflammatory cytokines (namely IL-1β, IL-6 and TNF-α), and Caspase-3, indicating cell apoptosis and also promoting the levels of vascular endothelial growth factor (VEGF) and its subtype receptor VEGFR-2 in the hippocampus. Moreover, the effects of rapamycin were linked to improvement of neurological deficits and increased brain water content observed in CA rats. In conclusion, activation of mTOR signal is engaged in pathophysiological process during CA-induced transient global ischemia and blocking mTOR pathway plays a beneficial role in regulating injured neuronal tissues and neurological deficits via PIC, apoptotic Caspase-3 and VEGF mechanisms. Targeting one or more of these specific mTOR pathways and its downstream signaling molecules may present new opportunities for neural dysfunction and vulnerability related to transient global ischemia.

Background Some of the thyroid disorders (TD) and Myasthenia gravis (MG) are autoimmune related disease. The purpose of the study to evaluate the relationship of MG with all morphological and functional thyroid disorders. Methods: We constructed a population-based cohort study during the period from January 2000-December 2002 by using reimbursement data from the Bureau National Health Insurance (NHI) system in Taiwan. Patients with TD and MG were identified by referring to the ICD-9-CM codes. (ICD-10-CM as reference) .The association of TD with MG occurred only in the same person within the study period. The Q value was used to measure the strength of disease-disease associations. Results We obtained 520628 TD and 7965 MG records for analysis. Diffuse toxic goiter had highest association rate, followed by nontoxic nodular goiter, simple goiter, chronic lymphocytic thyroiditis, thyroid cancer, and toxic nodular goiter. Female and older patients had a higher rate than their male and younger counterparts, respectively. Functional abnormalities revealed higher incidence of thyrotoxicosis and hypothyroidism in both sexes. We also found the strongest association in men with chronic thyroiditis, diffuse toxic goiter, thyrotoxicosis, acquired hypothyroidism, thyroid cancer, and simple goiter. While an intermediate association was observed in female with diffuse toxic goiter, in a male with toxic and nontoxic nodular/multinodular goiters, in female with thyrotoxicosis, thyroid cancer and acquired hypothyroidism. Conclusion This population based cohort study showed potential association of all types of TD with MG, and observed a higher association rate in female autoimmune TD whereas males showed a higher strength of association.

Connexin (Cx) 36 is known to be a component of gap junctions, and has been suggested to play an important role in epilepsy. In order to determine dynamic changes of Cx36 protein expression in epilepsy and investigate the role of Cx36 in electroencephalographic activity and pathogenesis, we utilized kainic acid (KA) to induce epileptogenesis. We found that epileptic discharges began 71.8 ± 23.7 s after KA administration. Spike frequency and amplitude of epileptiform activity reached maximal levels at 30 ± 5.2 min. The maximum level of spike frequency and amplitude of epileptiform activity was 13.9 ± 0.3 Hz and 198 ± 14.3mV respectively. Employing Western blotting and immunohistochemistry, we demonstrated that hippocampal Cx36 protein expression was significantly increased 6 h after KA kindling compared to control or sham groups, but decreased in 3 d and 7d groups. Our results suggested that the dynamic change of Cx36 expression may play an important role inepilepsy, and the specific manipulation of Cx36 expression may be a potential target for the treatment of epilepsy.

Intracerebral hemorrhage (ICH) is a subtype of stroke that is followed by primary and secondary brain injury. As a result of the injury, cell metabolism is disrupted and a series of stress responses are activated, such as endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), leading to the re-establishment of cell homeostasis or cell death. As an important mechanism of cell homeostasis, autophagy has been widely studied, and the associations between autophagy, ER stress, and the UPR have also been demonstrated. Whether these mechanisms are beneficial or detrimental remains a matter of controversy, but there is no doubt as to their vital functions. An understanding of the mechanisms of injury and recovery after ICH is crucial to develop therapeutic strategies. In this review, we summarize the related studies and highlight the roles of autophagy, ER stress, and the UPR in disease, especially in ICH. We also provide an overview of therapeutic approaches that target autophagy, and we discuss the prospects for modulating autophagy, ER stress, and UPR mechanisms in ICH therapy.

Sex-biased psychophysiology, behavior, brain function, and conditions are extensive, yet underlying structural brain mechanisms remain unclear. There is contradicting evidence regarding sexual dimorphism when it comes to brain structure, and there is still no consensus on whether or not there exists such a dimorphism for brain white matter. Therefore, we conducted a voxel-based morphometry (VBM) analysis along with global volume analysis for white matter across sex. We analyzed 384 T1-weighted MRI brain images (192 male, 192 female) to investigate any differences in white matter (WM) between males and females. In the VBM analysis, we found males to have larger WM, compared to females, in occipital, temporal, insular, parietal, and frontal brain regions. In contrast, females showed only one WM region to be significantly larger than males: the right postcentral gyrus in the parietal lobe region. Although, on average, males showed larger global WM volume, we did not find any significant difference in global WM volume between males and females.

Subarachnoid hemorrhage (SAH) is a common and frequently life-threatening cerebrovascular disease, which is mostly related with a ruptured intracranial aneurysm. Its complications include rebleeding, early brain injury, cerebral vasospasm, delayed cerebral ischemia, chronic hydrocephalus, and also non neurological problems. Non-coding RNAs (ncRNAs), comprising of microRNAs (miRNAs), small interfering RNAs (siRNAs) and long non-coding RNAs (lncRNAs), play an important role in intracranial aneurysms and SAH. Here, we review the non-coding RNAs expression profile and their related mechanisms in intracranial aneurysms and SAH. Moreover, we suggest that these non-coding RNAs function as novel molecular biomarkers to predict intracranial aneurysms and SAH, and may yield new therapies after SAH in the future.

Congenital Myasthenic Syndrome (CMS) is a group of inherited neuromuscular junction disorders caused by defects in several genes. Clinical features include delayed motor milestones, recurrent respiratory illnesses and variable fatigable weakness. The central nervous system involvement is typically not part of the CMS. We report here a Saudi girl with genetically proven Collagen Like Tail Subunit Of Asymmetric Acetylcholinesterase (COLQ) mutation type CMS who has global developmental delay, microcephaly and respiratory failure. We have reviewed the literature regarding COLQ-type CMS and to the best of our knowledge this is the first ever reported association of congenital myasthenia syndrome with microcephaly.

Clinicians often rely on selected small molecular compounds from body fluids for the detection, screening or monitoring of numerous life-threatening diseases. Among others, important monoamines – biogenic amines (BAs) – and their metabolites serve as sensitive biomarkers to study the progression or even early detection of on-going brain pathologies or tumors of neuroendocrine origins. Undertaking the task to optimize a reliable method for the simultaneous analysis of the most relevant BAs in biological matrices is of utmost importance for scientists. Hydrophilic interaction liquid chromatography (HILIC) with mass spectrometry (MS) detection provides a specific and sensitive technique for the separation and assessment of several neurotransmitter concentrations in body fluids (blood, urine, tissues). The present study was focused on the optimization of a straightforward, sensitive and reliable method for the simultaneous analysis of the ten most important BAs and their acidic metabolites from homogenates of rat brain tissues by use of HILIC-MS. Here, we present the optimized experimental workflow in terms of sample preparation, buffer compositions, HILIC and MS settings and data analysis. The presented method is reliable, straightforward and sensitive. Our method permits the unbiased, qualitative and quantitative determination of several BAs and their metabolites simultaneously. The optimized method was applied to the analysis of rat brain tissue samples from healthy hemispheres or those with induced transient ischemic attack (TIA). The undertaken pilot study demonstrated that the proposed approach could be applied to reveal the perturbation in neurotransmitters concentration after TIA in rat brains.

Background Patients with alcohol dependence (AD) are known to develop poor social skills, to report a higher number of adverse childhood experiences (ACEs) and to attempt suicide more frequently than the general population. The background for the association between ACEs and a higher risk of suicide still remains understudied. SSTR4 rs2567608 is a functional polymorphism of the gene for somatostatin receptor subtype 4, predominantly found in the CA1 hippocampus area and involved in memory formation. We hypothesize that the functional polymorphism SSTR4 rs2567608, general self-efficacy, and adverse childhood experiences influence the risk of suicide attempt in patients with AD. Methodology 176 patients with AD and 127 healthy controls were interviewed regarding 13 categories of ACEs and assessed with the General Self-Efficacy Scale. Genotyping for the SSTR4 rs2567608 polymorphism was performed according to the manufacturer’s standard PCR protocol. Results Patients with AD and the controls did not differ significantly according to the SSTR4 rs2567608 genotype and allele frequencies. Lower general self-efficacy, higher number of ACEs, and the SSTR4 rs2567608 TT genotype increased the risk of suicide attempt in patients with AD, and it persisted significant only in male patients with AD. Conclusions Our study supports previous findings on ACEs and general self-efficacy association with a risk for suicide. Additionally, we suggest that patients with AD of the SSTR4 rs2567608 TT genotype may be more vulnerable to ACEs and at a higher risk of suicide attempt.

Cognition is comprised of the faculties: perception, creativity, intuition, and ratiocination. Optimal levels of cognition are needed for independent functioning and balanced living. With an aging population that continues to grow, dietary supplements that tilt the balance towards maintenance of cognition are being marketed for vulnerable populations facing these challenges. Randomized clinical trials provide the causal inference necessary to define the efficacy of emerging nutraceuticals. Cognition testing, in particular, requires a battery of tests that encompass all brain regions involved in cognition so as to provide endpoints necessary for product validation. The lack of well controlled studies for comparison analyses, limited sample sizes, ambiguous dosages, and poor cognitive measures result in data that cannot be compared across studies to determine the efficacy of supplements claiming to enhance cognition. Clinical trials for the nutraceutical industry should consider the multifaceted nature of supplements, where clinical endpoints must be comprehensive while remaining feasible. Combining endpoints of cognition with physiological biomarkers of immunity and metabolism to arrive at a global index for cognitive health may be necessary for claim substantiation in order to fully justify and scientifically validate improvements in cognitive health. The issues and needs of a global index will be discussed here.

Objective To investigate the effect of mechanical thrombectomy with solitaire stent in the treatment of acute ischemic stroke with large cerebral artery occlusion. Methods Fifteen acute ischemic stroke patients with a proximal intracranial occlusion in the anterior circulation were included within 6 hours after symptom onset (unknown time of onset allowed in wake upstroke). Patients with a large infarct core or poor collateral circulation on computed tomography (CT) and CT angiography were excluded. All patients were measured by the National Institutes of Health Stroke Scale (NIHSS) before and 24 hours after the procedure. The primary outcomes were reperfusion at 24 hours and a Thrombolysis in Cerebral Infarction (TICI) score of 2b or 3 indicates successful reperfusion. Secondary outcomes included the functional score on the Modified Rankin Scale(MRS) and NIHSS score at 90 days. Good Functional Outcome (GFO), is defined as mRS0–2 at 90 days. Results The preoperative TICI grading of these 15 patients were all level 0.14 patients were level 2b to level 3 after the thrombectomy, 1 ipsilateral cervical carotid occlusion patient failed recanalization.14 patients with reperfusion at 24 hours showed good early neurologic improvement. The MRS score of all the 14 patients were<2 point at 90 days. There were no obvious adverse reactions and complications in these patients after mechanical thrombectomy. Conclusion The application of mechanical thrombectomy with solitaire stent for the treatment of acute ischemic stroke with large cerebral artery occlusion is safe and time-efficient, which could improve the recanalization rate, decrease or even eliminate the application of thrombolytic drugs and reduce the rate of intracranial hemorrhage. Awake stroke patient can also benefit from thrombectomy.

The present study evaluates the effect of grifolin (GFL) in oxygen/glucose deprivation (OGD) induced white matter lesion. Injury induced with OGD was found to be significant at the 9th h of OGD induction and the effect of GFL on the proliferation of oligodendrocyte precursor cells (OPCs) was assessed by CCK-8 and Hoechst 33258 assay at GFL 1, 5, 25, 50 and 100 μm concentrations. Whereas immunocytochemistry was performed for the assessment of survival and apoptosis of OPCs, western blot assay and RT-PCR were performed after 8th day of OGD injury for the estimation of expressions of myelin basic protein (MBP) and inhibitor of DNA binding 2 (Id2) in OPCs respectively. Results of the study suggests that treatment with GFL significantly enhances the survival rate and decreases the apoptosis of OPCs in OGD induced injury model. Immunocytochemical staining of Oligodendrocyte transcription factor (Olig2) and Bromodeoxyuridine (Brdu) shows that GFL treatment improves the proliferation of OPCs than OGD group. Moreover data of western blot assay suggested that treatment with GFL significantly enhances the expressions of MBP and Olig2 than OGD. It was observed that expressions of Id2 decreases and Olig2 enhances in GFL treated group than OGD group. Data of our study concludes that GFL enhances the differentiation and proliferation of OPCs in OGD-induced injury by altering the expressions of Id2 and Olig2.

This report evaluates the protective effect of caffeoylquinic acid (CA) injury to oligodendrocyte precursor cells (OPCs) by promoting the formation of oligodendrocytes. Neonatal rat brain was used to isolate primary OPCs and non-lethal CoCl2 was used to induce hypoxic stress to inhibit the differentiation of OPCs. Differentiation of OPCs was estimated by survival assay and the expressions of myelin-basic-protein (MBP). Moreover, the effect of CA on the Akt signanling pathway was also estimated in the presence and absence of LY294002 (PI3K/Akt inhibitor) and adrenomedullin (AM) receptor antagonist (AM22-52) by using western blot assay. It was observed that CA enhances the differentiation OPCs in CoCl2 induced hypoxic stress condition. However treatment with CA in presence of LY294002 and AM22-52 was not able to enhance the differentiation of OPCs. Moreover treatment with CA significantly enhances the phosphorylation of Akt and presence of LY294002 and AM22-52 inhibits it. This report concludes that CA effectively attenuates the injury of white matter (OPCs) by enhancing the differentiation of OPCs. It enhances the formation of oligodendrocytes by activating AM receptor and thereby accelerates the regeneration of neuron in pathological condition.

Background Verbal learning (VL) and fluency (VF) are prominent cognitive deficits in psychosis, of which the precise neuroanatomical contributions are not fully understood. We investigated the arcuate fasciculus (AF) and its associated cortical regions to identify structural abnormalities contributing to these verbal impairments in early stages of psychotic illness. Methods Twenty-six individuals with recent-onset psychosis and 27 healthy controls underwent cognitive testing (MATRICS Consensus Cognitive Battery) and structural/diffusion-weighted MRI. Bilaterally, AF anisotropy and cortical thickness, surface area and volume of seven cortical regions were investigated in relation to VL and VF performance in both groups. Results Reduced right superior temporal gyrus surface area and volume related to better VF in controls. In psychosis, greater right pars opercularis volume and reduced left lateralization of this region related to better VL, while greater right long AF fractional anisotropy and right pars orbitalis volume related to better VF, these findings not present in controls. Psychosis had reduced right pars orbitalis thickness compared to controls. Conclusion Anatomical substrates for normal processing of VL and VF appear altered in recent-onset psychosis. A possible aberrant role of the right hemisphere arcuate fasciculus and fronto-temporal cortical regions in psychosis may contribute to deficits in VL and VF.

Background Genome methylation may modulate synaptic plasticity, being a potential background for mental disorder. Adverse childhood experiences (ACEs), known to be frequently reported by patients with alcohol dependence (AD), have been proposed as one of environmental inequities influencing DNA methylation. The study is aiming 1.To assess a promoter region methylation in gene for somatostatin receptor subtype-4 ( SSTR4 ), a receptor for somatostatin, a neurotransmitter engaged in neuroplasticity and memory formation, in patients with AD; 2. To verify if SSTR4 promoter methylation is associated with ACEs and other selected environmental factors. Methodology: 176 patients with AD and 127 healthy controls were interviewed regarding 13 categories of ACEs; a structured self-reported questionnaire - to measure the sociodemographic and clinical characteristics; a module of Catalogue of Healthy Behavior – to assess nutritional health habits; the Alcohol Use Disorders Identification Test – to assess drinking severity. The SSTR4 promoter region methylation status was performed via methylation-specific PCR, and the genotyping for the SSTR4 rs2567608 functional polymorphism - according to the manufacturer’s standard PCR protocol. Results SSTR4 promoter region was found methylated in 21.6% patients with AD and 2.3% controls. None of following characteristics: current age, gender, term and kind of labor, 13 categories of childhood trauma, diet, alcohol drinking severity, age at alcohol drinking initiation, age at onset of problem drinking, cigarette smoking, and SSTR4 rs2567608 was a significant predictor for SSTR4 promoter region methylation. Conclusions SSTR4 promoter region methylation in here studied participants may be either inherited epigenetic modification or secondary, but not to here assessed variables.

Background The aim of this study was to test the General Oral Health Assessment Index Questionnaire (GOHAI) items for differential item functioning (DIF) according to demographic characteristics (gender, age) and mental health status (schizophrenic disorders versus general population) using Rasch analysis. Methods This is a cross-sectional study using aggregated baseline data from a validation study of the GOHAI in the French general population (GP) and similar validation study in persons with schizophrenia (PWS). DIF was tested using the Partial Credit Model. DIF were estimated in different groups of patients. Results The cohort comprised 363 persons: 65% were female, 83% were 25-45 years old and 30% were PWS.Five of the 12 items exhibited DIF. DIF effects were observed with schizophrenia for 3 items, with age for 3 items and with gender for 1 item. The variable “age” gave a significant explanation of the latent variable: the latent variable decreased with age (-0.40±0.08-p<0.001 for each increase of the age of 10 years). This decrease represented an effect size of 0.27 which can be qualified of a small to medium effect. The status of the individuals (GP versus PWS) and the gender did not significantly explain differences in the values of the latent variable. Conclusion The GOHAI scores may not be comparable across sub-groups defined by health status, age and gender without accounting for DIF. In the future, other studies should explore this way with other Oral Health related Quality of Life assessment tools and populations with mental illness.

Cationic arginine-rich and poly-arginine peptides (referred to as CARPs) have potent neuroprotective properties in in vitro excitotoxicity and in vivo models of stroke. Traumatic brain injury (TBI) shares many pathophysiological processes as stroke, including excitotoxicity. Therefore, we evaluated our lead peptide, poly-arginine R18, with the COG1410 and APP96-110 peptides, which have neuroprotective actions following TBI. In an in vitro cortical neuronal glutamic acid excitotoxicity injury model, R18 was highly neuroprotective and reduced neuronal calcium influx, while COG1410 and APP96-110 displayed modest neuroprotection and were less effective at reducing calcium influx. In an impact-acceleration closed-head injury model (Marmarou model), R18, COG1410, and APP96-110 were administered intravenously (300 nmol/kg) at 30 minutes after injury in male Sprague-Dawley rats. When compared to vehicle, no peptide significantly improved functional outcomes, however the R18 and COG1410 treatment groups displayed positive trends in the adhesive tape test and rotarod assessments. Similarly, no peptide had a significant effect on hippocampal neuronal loss, however a significant reduction in axonal injury was observed for R18 and COG1410. In conclusion, this study has demonstrated that R18 is significantly more effective than COG1410 and APP96-110 at reducing neuronal injury and calcium influx following excitotoxicity, and that both R18 and COG1410 reduce axonal injury following TBI. Additional dose response and treatment time course studies are required to further assess the efficacy of R18 in TBI.

Autism Spectrum Disorders subjects (ASD) are well known to have deficits in social interaction. We recorded simultaneously eye movements and postural sway during exploration of emotional faces in children with ASD and typically developing children (TD). We analyzed several postural and ocular parameters. The results showed that all postural parameters were significantly greater in children with ASD; ASD made significantly fewer saccades and had shorter fixation time than TD, particularly in the eyes, and especially for unpleasant emotions. These results suggest that poor postural control of ASD and their impaired visual strategies could be due to a lack of interest in social cognition, causing a delay in the development of the cortical areas, and thus could have an effect on their postural control.

Synesthesia is commonly thought to be a phenomenon of fixed associations between an outside inducer and a vivid concurrent experience. Hence, it has been proposed that synesthesia occurs due to additional connections in the brain with which synesthetes are born. Here we show that synesthesia can be a much richer and more flexible phenomenon with a capability to creatively construct novel synesthetic experiences as events unfold in people’s lives. We describe here cases of synesthetes who occasionally generate novel synesthetic experience, called one-shot synesthesias. These synesthetic experiences seem to share all the properties with the classical synesthetic associations except that they occur extremely rarely, people recalling only a few events over the lifetime. It appears that these one-shots are not created at random but are instead responses to specific life events. We contrast the properties of those rare synesthetic events with other, more commonly known forms of synesthesia that also create novel synesthetic experiences, but at a high rate—sometimes creating novel experiences every few seconds. We argue that one-shot synesthesias indicate that synesthetic associations are by their nature not prewired at birth but are dynamically constructed through mental operations and according to the needs of a synesthetic mind. Our conclusions have implications for understanding the biological underpinnings of synesthesia and the role the phenomenon plays in the lives of people endowed with synesthetic capacities.

The present investigation evaluates the neuroprotective effect of chlorogenic acid (CA) in alcohol-induced brain damage in neonatal rats. Ethanol (12 % v/v, 5 g/kg) was administered orally in the wistar rat pups on postnatal days (PD) 7-9. Chlorogenic acid (100 and 200 mg/kg, p.o.) was administered continuously from PD 6 to 28. Cognitive function was estimated by Morris water maze (MWM) test. However, activity of acetylcholinesterase, inflammatory mediators, parameters of oxidative stress and activity of caspase-3 enzyme was estimated in the tissue homogenate of cerebral cortex and hippocampus of ethanol-exposed pups. It has been observed that treatment with CA attenuates the altered cognitive function in ethanol-exposed pups. There was a significant decrease in the activity of acetylcholinesterase in the CA treated group compared to the negative control group. However, treatment with CA significantly ameliorates the increased oxidative stress and concentration of inflammatory mediators in the brain tissues of ethanol-exposed pups. Activity of caspase-3 enzyme was also found significantly decreased in the CA treated group compared to the negative control group. The present study concludes that CA attenuates the neuronal damage induced in alcohol exposed neonatal rat by decreasing the apoptosis of neuronal cells.

Translational studies comparing imaging data of animals and humans have gained increasing scientific interests. With this upcoming translational approach, however, identifying harmonized statistical analysis as well as shared data acquisition protocols and/or combined statistical approaches is necessary. Following this idea, we applied Bayesian Adaptive Regression Splines (BARS), which have until now mainly been used to model neural responses of electrophysiological recordings from rodent data, on human hemodynamic responses as measured via fMRI. Forty-seven healthy subjects were investigated while performing the Attention Network Task in the MRI scanner. Fluctuations in the amplitude and timing of the BOLD response were determined and validated externally with brain activation using GLM and also ecologically with the influence of task performance (i.e. good vs. bad performers). In terms of brain activation, bad performers presented reduced activation bilaterally in the parietal lobules, right prefrontal cortex (PFC) and striatum. This was accompanied by an enhanced left PFC recruitment. With regard to the amplitude of the BOLD-signal, bad performers showed enhanced values in the left PFC. In addition, in the regions of reduced activation such as the parietal and striatal regions, the temporal dynamics were higher in bad performers. Based on the relation between BOLD response and neural firing with the amplitude of the BOLD signal reflecting gamma power and timing dynamics beta power, we argue that in bad performers, an enhanced left PFC recruitment hints towards an enhanced functioning of gamma-band activity in a compensatory manner. This was accompanied by reduced parieto-striatal activity, associated with increased and potentially conflicting beta-band activity.

Objective This study investigated the effects of calcium on fluorosis-induced impairment in learning and memory of offspring rats. Methods Seventy-five newly weaned female Sprague–Dawley (SD) rats were randomly divided into five groups as follows: Control group (Control) drank tap water, and ate the normal diet (calcium content of 0.79%); fluoride group (F) drank 100 mg/L NaF solution, and ate the normal diet; low calcium group (LCa) drank tap water, and ate the low calcium diet (calcium content of 0.063%); low calcium fluoride group (F+LCa) drank 100 mg/L NaF solution, and ate the low calcium diet; high calcium fluoride group (F+HCa) drank 100 mg/L NaF solution, and ate the high calcium diet (calcium content of 7%). After exposing rats to fluoride for three months, male and female rats were mated and 14 and 28 days old offspring were obtained as experimental subjects. Examinations determined the submicroscopic parameters of the synaptic interface and expression levels of specific proteins: doublecortin (DCX) and synaptophysin (p38). Results (1) High fluorosis significantly reduced synapse density, length of synaptic active zone, thickness of postsynaptic density, and led to abnormal changes in the structural parameter of synaptic gap width, which was significantly reduced or increased. High dietary calcium significantly reversed the abnormal changes in structural parameters, and low calcium aggravated these variations. (2) Dietary calcium resulted in nonsignificant effect on expression levels of DCX and p38. Conclusion The results suggested that dietary calcium significantly affected hippocampal synaptic plasticity of offspring of mothers exposed to water fluorosis, but its molecular mechanism may not be related to the expression of DCX and p38 in the brain. The findings also demonstrate the important effects of maternal exposure to water fluorosis on offspring brain functions before water improvement.

Objective The pathogenesis of depression is not fully understood, but studies have suggested that higher circulating levels of C reactive protein (CRP) might relate to depression occurrence. However, due to the highly variability of individual patients’ conditions, the results to date are inconsistent. Considering Single nucleotide polymorphisms (SNPs) of CRP gene have also been suggested to predict plasma CRP levels. In the present study, we hypothesize that inherited CRP allelic variations may co-vary with depressive symptomatology. Methods We recruited patients with a diagnosis of depression, with or without family depression history. We then detected serum CRP levels, as well as genome CRP SNPs from participants of this project. Results We found a significantly higher circulating CRP levels in patients with a positive family history. Furthermore, we also identified certain inherited CRP SNPs (A allele in rs1417938 and C allele in rs1205) which could up-regulate serum CRP levels and thus be associated with depression occurrence. Conclusion Our findings raise new evidence for the relationship between circulating CRP level and depression occurrence.

Background Pineal area tumors are challenging for surgery due to their location. However, the removal of the lesion is critical for further treatment and survival of the patients Material and methods 22 patients with pineal area tumors were surgically treated via keyhole medial suboccipital craniotomy and supracerebellar midline approach All the patients were operated in the sitting position with the use of operating microscope and microsurgical technique. Results All patients survived surgery in a perfect condition, and no one patient worsened after surgery. No complications due to the sitting position were noted. Conclusions Surgical removal of pineal area tumors via small suboccipital craniotomy is safe and with the use of microsurgical techniques the results of surgical treatment are excellent. The sitting position of the patients gives a better view to the surgeon. We did not observe any intraoperational complications due to the sitting position.

The objective of this study was to evaluate the piglet and the mouse as model systems for preterm cortical development. According to the clinical context, we used non invasive EEG recordings. As a prerequisite, we developed miniaturized Ag/AgCl electrodes for full band EEG recordings in mice and verified that Urethane had no effect on EEG band power. Since mice are born with a “preterm” brain, we evaluated three age groups: P0/P1, P3/P4 and P13/P14. Our aim was to identify EEG patterns in the somatosensory cortex which are distinguishable between developmental stages and represent a physiologic brain development. In mice, we were able to find clear differences between age groups with a simple power analysis of EEG bands and also for phase locking and power spectral density. Interhemispheric coherence between corresponding regions can only be seen in two week old mice. The canolty maps for piglets as well as for mice show a clear PAC (phase amplitude coupling) pattern during development. From our data it can be concluded that analytic tools relying on network activity, as for example PAC (phase amplitude coupling) are best suited to extract basic EEG patterns of cortical development across species.