Band 29, Heft 3

One of the approaches to the research of the problem of aging is the study of genetic pathologies leading to accelerated aging, such as the Hutchinson-Gilford progeria syndrome, Werner syndrome, and Down syndrome. Probably, this approach can be used in an attempt to understand the neuronal mechanisms underlying normal and pathological brain aging. The analysis of the current state of scientific knowledge about these pathologies shows that in the Hutchinson-Gilford progeria and Werner syndrome, the rate of brain aging is significantly lower than the rate of whole body aging, whereas in Down syndrome, the brain ages faster than other organs due to amyloid-beta accumulation and chronic oxidative stress in the brain tissue. The main point of a previously proposed hypothesis is that the aging of higher animals and humans is associated with an increased level of reactive oxygen species in mitochondria with age, which activates apoptosis, thus reducing the number of functioning cells.

Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders mainly affecting elderly people. It is characterized by progressive loss of memory and cognitive function. More than 95% of AD cases are related to sporadic or late-onset AD (LOAD). The etiology of LOAD is still unclear. It has been reported that environmental factors and epigenetic alterations play a significant role in AD pathogenesis. Furthermore, recently, genome-wide association studies (GWAS) identified 10 novel risk genes: ABCA7 , APOE , BIN1 , CD2AP , CD33 , CLU , CR1 , MS4A6A , MS4A4E , and PICALM , which play an important role for LOAD. In this review, the therapeutic approaches of AD by epigenetic modifications have been discussed. Nowadays, HDAC inhibitors have clinically proven its activity for epigenetic modifications. Furthermore, we try to establish the relationship between HDAC inhibitors and above mentioned LOAD risk genes. Finally, we are hoping that this review may open new area of research for AD treatment.

Working memory (WM) is an important cognitive function that is necessary to perform our daily activities. The present review briefly describes the most accepted models underlying WM and the neural networks involved in its processing. The review focuses on how the neurophysiological mechanisms develop with age in the periods from childhood to adolescence and young adulthood. Studies using behavioral, neuroimaging, and electrophysiological techniques showed the progress of WM throughout the development. The present review focuses on the neurophysiology of the basic processes underlying WM operations, as indicated by electroencephalogram-derived signals, in order to take advantage of the excellent time resolution of this technique. Children and adults use similar cerebral mechanisms and areas to encode, recognize, and keep the stimuli in memory and update the WM contents, although adults rely more on anterior sites. The possibility that a functional reorganization of WM brain processing occurs around the adolescent period is suggested, and would partly justify the high prevalence of the emergence of mental pathology in the adolescent period.

Although drug-abusing women try to moderate their drug and alcohol use during pregnancy, they often relapse at a time when childcare needs are high and maternal bonding is critical to an infant’s development. In the clinical setting, the search for the neural basis of drug-induced caregiving deficits is complex due to several intervening variables. Rather, the preclinical studies that control for drug dose and regimen, as well as for gestational and postpartum environment, allow a precise determination of the effects of drugs on maternal behaviour. Given the relevance of the issue, this review will gather reports on the phenotypic correlates of maternal behaviour in preclinical studies, and focus on the detrimental consequences on the mother-infant interaction exerted by the perinatal use of alcohol, nicotine, cannabis, cocaine and stimulants and opiates. The drug-induced disruptions of this maternal repertoire are associated with adverse maternal and infant outcomes. A comprehensive overview will help promote the refinement of the treatment approaches toward maternal drug use disorders and maternal misbehaviour, in favour of augmented parenting resiliency.

Tuberous sclerosis complex (TSC) is an auto-somal-dominant inherited condition with an incidence of approximately 1:6000 births, characterised by deregulated mTOR activity with multi-site hamartomas. Subependymal giant cell astrocytomas (SEGA) are one such hamartoma, affecting up to 24% of patients with TSC. Their intraventricular location may lead to life-threatening obstructive hydrocephalus. Current management is hampered by a lack of understanding regarding the natural history, behaviour and growth patterns of SEGA. We review the current literature to summarise what is known about SEGA in the following areas: (1) diagnostic criteria, (2) prevalence, (3) origin, (4) imaging characteristics, (5) growth rate, (6) genotype-phenotype correlation, (7) congenital SEGA and (8) SEGA as a marker of severity of other TSC manifestations.

A very challenging problem in the domain of the cognitive neurosciences is to explain why herpes simplex encephalitis and semantic dementia show, respectively, a category-specific semantic disorder for biological entities and an across-categories semantic disruption, despite highly overlapping areas of anterior temporal lobe damage. The aim of the present review consisted in trying to make a separate survey of anatomo-clinical investigations (single-case studies and group studies) and of activation studies, in order to analyse the factors that could explain these different patterns of semantic disruption. Factors taken into account in this review were laterality of lesions, disease aetiology, kind of brain pathology and locus of damage within the temporal lobes. Locus of damage within the temporal lobes and kind of brain pathology seemed to play the most important role, because in patients with herpes simplex encephalitis and category-specific semantic disorder for biological entities the lesions prevailed in the anteromedial temporal lobes. Furthermore, the neuropathology concerned both the anterior temporal cortices and the white matter pathways connecting these areas with the posterior visual areas, whereas in semantic dementia the inferior longitudinal fasciculus involvement was restricted to the rostral temporal lobe and did not extend into the cortically uninvolved occipital lobe.

Injury to tissues is a major clinical challenge due to the limited regenerative capacity of endogenous cells. Stem cell therapy is evolving rapidly as an alternative for tissue regeneration. However, increasing evidence suggests that the regenerative ability of stem cells is mainly mediated by paracrine actions of secretome that are generally secreted by the cells. We aimed to systematically evaluate the efficacy of dental stem cell (DSC)-conditioned medium in in vivo animal models of various tissue defects. A total of 15 eligible studies was included by searching Pubmed, Scopus and Medline databases up to August 2017. The risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation risk of bias tool. Of 15 studies, seven reported the therapeutic benefit of the conditioned medium on neurological diseases and three reported on joint/bone-related defects. Two interventions were on liver diseases, whereas the remaining three addressed myocardial infarction and reperfusion, lung injury and diabetes. Nine studies were performed using mouse models and the remaining six studies used rat models. The methodological quality of the studies was low, as most of the key elements required in reports of preclinical studies were not reported. The findings of this review suggested that conditioned medium from DSCs improved tissue regeneration and functional recovery. This current review strengthens the therapeutic benefit of cell-free product for tissue repair in animal models. A well-planned study utilizing validated outcome measures and long-term safety studies are required for possible translation to clinical trials.

Accumulating experimental data suggests a number of successful drug targets against epilepsy which eventually failed in the clinical setup. Mammalian target of rapamycin inhibitors, multi-drug resistance transporter inhibitors, cyclo-oxygenase-2 inhibitors, statins, etc. are the most promising and well studied among them. Drugs aiming at these targets produced beneficial response in most of the in vitro and in vivo seizure models. However, in certain situations, they have produced differential rather controversial results. Their effects varied with the seizure model, species, time and route of administration, different drugs from the same class, etc. This review emphasises on such drugs which presented with variability in their beneficial effects against seizures and epilepsy. This review critically summarises the preclinical evidence of these targets in the context of seizures and the probable reasons for their variability and clinical failures.

Among the highest incidences of schizophrenia is the one documented in second-generation migrants of African descent in the Western countries. Interestingly, people of African and European ancestry demonstrate significant genetic-based differences in immune system regulation and response. As a result, the pro-inflammatory phenotype is more pronounced in people of African descent than it is in Europeans. At the same time, the role of the immune system in the etiology of schizophrenia is gaining increased recognition. Here, we propose that the population-specific genetic variation within the immune system interacts with unfavourable environments to contribute to a higher risk of schizophrenia in people of African ancestry. Our hypothesis is supported by recent findings from two separate fields of research−population genetics and psychoneuroimmunology. Moreover, we highlight the need to include African populations in genetic studies of schizophrenia.