Volume 5, Issue 3

Recognition of emotional facial expressions is based on simulation and mirroring processes, and the premotor cortex is supposed to support this simulation mechanism. The role of this prefrontal area in processing emotional faces with different valence (anger, fear, happiness and neutral) was explored taking into account the effect of the lateralization model (more right-side activation for negative emotions; more left-side activation for positive emotions) of face processing and anxiety level (high vs low). High-frequency repetitive transcranial magnetic stimulation (rTMS, 10 Hz) was applied to the left prefrontal area to induce an increased activation response within the left premotor cortex. Twenty-nine subjects, who were divided into two different groups depending on their anxiety level (high/low anxiety; State-Trait-Anxiety Inventory (STAI), were asked to detect emotion / no emotion. Accuracy (AcI) and response times (RTs) were considered in response to the experimental conditions. A general significant increased performance was found in response to positive emotions in the case of left-side stimulation. Moreover, whereas high-anxiety subjects revealed a significant negative-valence bias in absence of stimulation, they showed a more significant AcI increasing and RTs decreasing in response to positive emotions in case of left premotor brain activation. The present results highlight the role of the premotor system for facial expression processing as a function of emotional type, supporting the existence of a valence-specific lateralized system within the prefrontal area. Finally, a sort of “restoring effect” induced by TMS was suggested for high-anxiety subjects.

The biological markers for schizophrenia (SZ) and bipolar disorder (BD) would represent a precious tool in evaluating the risk for the development of these common neuropsychiatric diseases and, possibly, in the prevention of either disease episodes and/or treatment efficiency monitoring. Since both SZ and BD are diseases with a significant genetic component, the research over the last decades has focused on the genes with altered function in the central nervous system (CNS) of individuals suffering from these illnesses. Recently, however, small non-coding RNA molecules (microRNAs, miRNAs, miRs) were shown to regulate the expression of human CNS genes involved in cell processes and functions negatively affected in neuropsychiatric disorders, including synaptic development and maturation, learning and memory. Differentially expressed sets of miRNAs have been reported in the tissues of SZ and BD patients in comparison to controls suggesting the emergence of a novel class of potential biomarkers. Here we review the reports on the changes in miRNA expression in postmortem brain tissue and peripheral blood in SZ and BD. We also evaluate the potential of miRNA packaged in exosomes, signaling vesicles released by neurons and glia, to contribute to the disaggregation of the molecular machinery underlying mental disorders and provide clinically useful biomarkers.

Oxidative stress is known to be a key factor in the pathogenesis of Parkinson’s disease (PD). Neuronal redox status is maintained by glucose metabolism via the pentose-phosphate pathway and it is known that disruption of glucose metabolism is damaging to neurons. Accumulating evidence supports the idea that glucose metabolism is altered in PD and dysregulation of the pentose-phosphate pathway in this disease has recently been shown. In this review, we present an overview of the literature regarding neuronal glucose metabolism and PD, and discuss the implications of these findings for PD pathogenesis and possible future therapeutic avenues.

Environmental enrichment aims to improve the well-being of laboratory animals and provides an opportunity to improve experimental reliability and validity. Animals raised in more stimulating environments have improved learning and memory as well as more complex brain architecture. However, the effects of environmental enrichment on motor performance, anxiety and emotional development have been poorly studied. Moreover, most investigators studying the effects of enrichment provide extremely large and complex housing conditions to maximize the likelihood of finding effects. These situations are difficult to replicate across animal facilities and are not operationally practical. In this experiment, we investigated how simple, inexpensive disposable shelterstyle enrichment items alter behavior in C57Bl/6 and 129S6 mice. Breeding pairs were established in the presence of a Ketchum “Refuge”, Shepherd Shack “Dome”, or no enrichment. Offspring were assessed neurobehaviorally, either just after weaning (pre-adolescent, P22–P25), or as young adults (P60–P90). Major strain differences were observed in open field activity, elevated maze exploration, and Y-maze activity levels. The presence of the Refuge and/or Dome enrichment shelters significantly altered motor activity, coordination and some measures of anxiety. Mice housed in the presence of shelters were also less dominant than control mice in a tube test assay. Our experiments provide a detailed analysis of the effects of inexpensive and practical methods of housing enrichment on biobehavioral phenotypes in these two commonly used strains of laboratory mice, and suggest that the effects of these shelters on mouse neurobiology and behavior need to be rigorously analyzed before being adopted within vivariums.

Aside from the well-known amyloid beta and tau pathologies found in Alzheimer’s disease (AD), neuroinflammation is a well-established aspect described in humans and animal models of the disease. Inflammatory perturbations are evident not only in neurons, but also in non-neuronal cells and cytokines in the AD brain. Although the amyloid hypothesis implicates amyloid beta (Aβ) as the prime initiator of the AD, brain inflammation in AD has a complex relationship between Aβ and tau. Using our work with the 5-lipoxygenase protein as an example, we suggest that at least in the case of AD, there is an interdependent and not necessarily hierarchical pathological relationship between Aβ, tau and inflammation.

Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by normal memory loss and cognitive impairment in humans. Many drug targets and disease-modulating therapies are available for treatment of AD, but none of these are effective enough in reducing problems associated with recognition and memory. Potential drug targets so far reported for AD are β-secretase, Γ-secretase, amyloid beta (Aβ) and Aβ fibrils, glycogen synthase kinase-3 (GSK-3), acyl-coenzyme A: cholesterol acyl-transferase (ACAT) and acetylcholinesterase (AChE). Herbal remedies (antioxidants) and natural metal-chelators have shown a very significant role in reducing the risk of AD, as well as lowering the effect of Aβ in AD patients. Researchers are working in the direction of antisense and stem cell-based therapies for a cure for AD, which mainly depends on the clearance of misfolded protein deposits — including Aβ, tau, and alpha-synuclein. Computational approaches for inhibitor designing, interaction analysis, principal descriptors and an absorption, distribution, metabolism, excretion and toxicity (ADMET) study could speed up the process of drug development with higher efficacy and less chance of failure. This paper reviews the known drugs, drug targets, and existing and future therapies for the treatment of AD.

Patients with a neurologically based loss of tactile processing on the contralesional side of the body can firmly deny the deficit (i.e., anosognosia for hemianesthesia). Previous studies attempted to feature the disease in both clinical and anatomo-functional terms. However, the picture is still incomplete and, most importantly, to date it is unclear whether and to which extent it can shed light on the mechanisms subserving tactile processing in the intact brain. Here we will briefly review the literature and we will put forward a possible anatomo-functional interpretation of anosognosia for hemianesthesia.

Cancer survivors treated with chemotherapy frequently complain about impairment of cognitive functions including attention and memory. While the contribution of factors like psychological distress, anxiety or fatigue to this “chemobrain” syndrome has been discussed, studies in rodents have demonstrated the toxicity of various chemotherapeutic substances to the adult central nervous system. In humans, structural brain imaging has revealed both reduced gray and white matter volume and decreased white matter integrity related to chemotherapeutic treatment. Studies of brain function have found alterations in brain activation patterns during different types of tasks. Nevertheless, further clinical research using prospective designs in larger samples is required to better understand the relationship between chemotherapy and cognitive deficits. Variables that need to be considered more systematically include drug dose, genetic variations, and psychological factors. Assessing both electroencephalographic and hemodynamic responses during tasks at different stages of the processing hierarchy and at different difficulty levels should help in pinpointing the cortical processes affected by chemotherapy.