The Neuroscientist

Physical exercise is known to exert various beneficial effects on brain function and bodily health throughout life. In biomedical research, these effects are widely studied by introducing running wheels into the cages of laboratory rodents. Yet, although rodents start to run in the wheels immediately, and perform wheel-running excessively on a voluntary basis, the biological significance of wheel-running is still not clear. Here, we review the current literature on wheel-running and discuss potentially negative side-effects that may give cause for concern. We particularly emphasize on analogies of wheel-running with stereotypic and addictive behavior to stimulate further research on this topic.

In recent years, the importance of the cellular redox status for neural stem cell (NSC) homeostasis has become increasingly clear. Similarly, the transcription factor and tumor suppressor p53 has been implicated in the regulation of cell metabolism, in antioxidant response, and in stem cell quiescence and fate commitment. Here, we explore the known and putative functions of p53 in antioxidant response and metabolic control and examine how reactive oxygen species, p53, and related cellular signaling may regulate NSC homeostasis, quiescence, and differentiation. We also discuss the role that PI3K-Akt-mTOR signaling plays in NSC biology and oxidative signaling and how p53 contributes to the regulation of this signaling cascade. Finally, we invite reflection on the several unanswered questions of the role that p53 plays in NSC biology and metabolism, anticipating future directions.

Immune activity in the CNS parenchyma under various acute and chronic neurodegenerative conditions has been often interpreted as a sign of pathological inflammation. The apparent resemblance of the local neuroinflammatory processes to autoimmune diseases, such as multiple sclerosis (MS), generated the view that, despite differences in etiology and pathology, neurodegenerative disorders with a local inflammatory component can benefit from systemic anti-inflammatory therapy. In addition, as CNS self-reactive T cells are associated with the etiology of MS, autoimmunity was assumed to solely reflect pathology, and therefore, was universally linked to autoimmune disease. Yet, it is becoming increasingly clear that CNS-specific T cells, along with circulating and local innate immune cells, can enhance CNS healing processes following non-infectious injuries, or any deviation from homeostasis, including chronic pathological conditions. Here, we discuss the theory of “protective autoimmunity,” which describes the activity of an immune cell network encompassing effector and regulatory T cells with specificity for CNS antigens, in CNS maintenance and repair. Such an immune network, evoked in response to external and internal threats, functions in a tightly regulated way, ensuring restoration of the brain’s equilibrium and return to homeostasis.

Stroke is a common problem, and with an aging population, it is likely to become more so. Outcomes from stroke are wide ranging from death to complete recovery, but the majority result in severe motor impairments that affect quality of life and become a burden on health care systems, family, and friends. Therapeutically, removal of thromboses can greatly improve outcomes, but for many stroke sufferers, the only currently available therapy is rehabilitative training in which spared brain areas and fiber tracts are strengthened and trained to take over new functions. Experimental data in animals show that this is in part based on changes in the connectivity of the brain and spinal cord and on the growth of new nerve fiber branches, a process called structural plasticity. So, just how plastic is the brain after a stroke? In this review, we explore the factors that affect plasticity after strokes, such as age and the overall size and location of the lesion. We discuss the peri-infarct area as extensive research has shown that processes occurring there are likely to be involved mechanistically in plastic changes in cortical circuitry. Finally, we review promising interventions being tested preclinically and discuss those that have been translated into clinical research.

Initially discovered as a potent neurite outgrowth inhibitor in the central nervous system (CNS), Nogo-A has emerged as a multifunctional protein. Involvement of this protein has been demonstrated in numerous developmental processes, ranging from cell migration, axon guidance and fasciculation, dendritic branching and CNS plasticity to oligodendrocyte differentiation and myelination. Although initially necessary and beneficial for shaping and later maintaining CNS structure and functionality, the growth restricting properties of Nogo-A can have negative effects on nervous system injury or disease. Hence, correlating with its various neurobiological roles, Nogo-A was implicated in a range of CNS disturbances, including trauma such as spinal cord injury or stroke, neurodegenerative diseases such as Alzheimer’s disease, amyotrophic lateral sclerosis or multiple sclerosis, or in schizophrenia. In this review, we summarize the current state of knowledge for Nogo-A’s involvement in these nervous system diseases and perturbations and discuss the possible underlying mechanisms. Furthermore, we provide a comprehensive overview on molecular signaling pathways as well as structural properties identified for Nogo-A and point to open questions in the field.

The rapid development of social media and social networking sites in human society within the past decade has brought about an increased focus on the value of social relationships and being connected with others. Research suggests that we pursue socially valued or rewarding outcomes—approval, acceptance, reciprocity—as a means toward learning about others and fulfilling social needs of forming meaningful relationships. Focusing largely on recent advances in the human neuroimaging literature, we review findings highlighting the neural circuitry and processes that underlie pursuit of valued rewarding outcomes across non-social and social domains. We additionally discuss emerging human neuroimaging evidence supporting the idea that social rewards provide a gateway to establishing relationships and forming social networks. Characterizing the link between social network, brain, and behavior can potentially identify contributing factors to maladaptive influences on decision making within social situations.

The natural complexity of the brain, its hierarchical structure, and the sophisticated topological architecture of the neurons organized in micronetworks and macronetworks are all factors contributing to the limits of the application of Euclidean geometry and linear dynamics to the neurosciences. The introduction of fractal geometry for the quantitative analysis and description of the geometric complexity of natural systems has been a major paradigm shift in the last decades. Nowadays, modern neurosciences admit the prevalence of fractal properties such as self-similarity in the brain at various levels of observation, from the microscale to the macroscale, in molecular, anatomic, functional, and pathological perspectives. Fractal geometry is a mathematical model that offers a universal language for the quantitative description of neurons and glial cells as well as the brain as a whole, with its complex three-dimensional structure, in all its physiopathological spectrums. For a holistic view of fractal geometry of the brain, we review here the basic concepts of fractal analysis and its main applications to the basic neurosciences.