Neurogenesis

The use of transcranial low-level laser (light) therapy (tLLLT) to treat stroke and traumatic brain injury (TBI) is attracting increasing attention. We previously showed that LLLT using an 810-nm laser 4 h after controlled cortical impact (CCI)-TBI in mice could significantly improve the neurological severity score, decrease lesion volume, and reduce Fluoro-Jade staining for degenerating neurons. We obtained some evidence for neurogenesis in the region of the lesion. We now tested the hypothesis that tLLLT can improve performance on the Morris water maze (MWM, learning, and memory) and increase neurogenesis in the hippocampus and subventricular zone (SVZ) after CCI-TBI in mice. One and (to a greater extent) three daily laser treatments commencing 4-h post-TBI improved neurological performance as measured by wire grip and motion test especially at 3 and 4 weeks post-TBI. Improvements in visible and hidden platform latency and probe tests in MWM were seen at 4 weeks. Caspase-3 express...

Glial-derived neurotrophic factor (GDNF) promotes both sensory and motor neuron survival. The delivery of GDNF to the peripheral nervous system has been shown to enhance regeneration following injury. In this study we evaluated the effect of affinity-based delivery of GDNF from a fibrin matrix in a nerve guidance conduit on nerve regeneration in a 13 mm rat sciatic nerve defect. Seven experimental groups were evaluated which received GDNF or nerve growth factor (NGF) with the delivery system within the conduit, control groups excluding one or more components of the delivery system, and nerve isografts. Nerves were harvested 6 weeks after treatment for analysis by histomorphometry and electron microscopy. The use of the delivery system (DS) with either GDNF or NGF resulted in a higher frequency of nerve regeneration vs. control groups, as evidenced by a neural structure spanning the 13 mm gap. The GDNF DS and NGF DS groups were also similar to the nerve isograft group in measures of nerve fiber density, percent neural tissue and myelinated area measurements, but not in terms of total fiber counts. In addition, both groups contained a significantly greater percentage of larger diameter fibers, with GDNF DS having the largest in comparison to all groups, suggesting more mature neural content. The delivery of GDNF via the affinity-based delivery system can enhance peripheral nerve regeneration through a silicone conduit across a critical nerve gap and offers insight into potential future alternatives to the treatment of peripheral nerve injuries.

Research studies suggest that glutamate dysfunction, in particular N-methyl-D-aspartate receptors (NMDARs) abnormalities, may be involved in the pathophysiology of major neuropsychiatric conditions. Increased glutamatergic excitotoxic activity may be found in some brain circuits of patients with major depression. According to several published reports, NMDAR antagonists may exert antidepressant activity, but the molecular changes associated with abnormal glutamatergic neurotransmission remain unclear. We have critically reviewed the current literature in order to investigate the role of NMDAR antagonists in major depression. NMDAR antagonists, such as ketamine, may be considered novel and promising pharmacological options for the rapid treatment of treatment-resistant depression patients. This is in contrast to the delayed action of the currently available antidepressant medications. Studies suggest that glutamatergic receptor modulation may enhance neuroplasticity mechanisms and ne...

We are facing an obesity epidemic, and obesity itself and its close companion, type 2 diabetes, are independent risk factors for neurodegeneration. While most medical treatments fail to induce a clinically meaningful improvement in neurodegenerative disorders, lifestyle interventions have emerged in the spotlight. A recently rediscovered approach is intermittent fasting (IF), which, compared to the classic caloric restriction regimens, limits only the time of eating, rather than the number of calories allowed per day. There is already a large amount of evidence from preclinical and clinical studies showing the beneficial effects of IF. In this review, we specifically focus on the effects of IF on brain metabolism. Key molecular players modified during IF and involved in its beneficial central effects (ketone bodies, BDNF, GABA, GH/IGF-1, FGF2, sirtuin-3, mTOR, and gut microbiota) are identified and discussed. Studies suggest that IF induces several molecular and cellular adaptations...

Microglia cells are the macrophages of the central nervous system with a crucial function in the homeostasis of the adult brain. However, recent studies showed that microglial cells may also have important functions during early embryonic central nervous system development. In this review we summarize recent works on the extra embryonic origin of microglia, their progenitor niche, the pattern of their invasion of the embryonic central nervous system and on interactions between embryonic microglia and their local environment during invasion. We describe microglial functions during development of embryonic neuronal networks, including their roles in neurogenesis, in angiogenesis and developmental cell death. These recent discoveries open a new field of research on the functions of neural-microglial interactions during the development of the embryonic central nervous system.

Free will designates the possibility of conscious and free choice of the subject, as well as his real possibility to act. The topic has a special medical and social relevance as it is directly connected to how the subject's responsibility (moral, legal, medical) for his own actions are understood, but also the possibility (real or illusory) of intervention in his own life. Free will has received various philosophical, psychological, legal and interdisciplinary approaches in recent decades. In this article we shall inventory some results from the area of neuroscience that we consider relevant in the analysis of free will, research and clinical studies that highlight various effects caused by voluntary actions, consciously repeated by the subject. Some psychotherapeutic interventions, the process of awareness, learning, attention monitoring, visualization, some forms of meditation, and the changes that these practices produce in the processes of neurogenesis, neuroplasticity and epigenetics, in terms of health and quality of life are analysed. Since these interventions involve the conscious participation of the subject and his voluntary action, we consider that the discussed results are relevant in the debate on free will. The study also highlights the importance of education and social knowledge, as well as the need to promote participatory prevention and therapy, involving the subject in increasing the quality of life and health, through public messages that emphasize the responsibility of each person for their own choices and actions and the impact they have on his life.

Liberul arbitru desemnează posibilitatea alegerii conștiente și libere a subiectului, precum și posibilitatea lui reală de a acționa. Tema prezintă o relevanță medicală și socială deosebită, întrucât are implicații directe asupra modului în care sunt înțelese responsabilitatea subiectului (morală, juridică, medicală) pentru propriile sale acțiuni, dar și posibilitatea (reală sau iluzorie) de intervenție în planul propriei vieți.
În ultimele decenii, diverse abordări filosofice, psihologice, juridice și interdisciplinare s-au pronunțat cu privire la liberul arbitru. În articolul de față, inventariem câteva rezultate din aria neuroștiințelor pe care le considerăm relevante în analiza liberului arbitru. Este vorba despre cercetări și studii clinice care evidențiază diverse efecte cauzate de acțiunile voluntare, repetate în mod conștient de către subiect. Sunt aduse în discuție unele intervenții psihoterapeutice, procedeul conștientizării, învățarea, monitorizarea atenției, vizualizarea, unele forme de meditație și modificările pe care aceste practici le produc la nivelul proceselor neurogenezei, neuroplasticității și epigenetice, în planul sănătății și al calității vieții. Întrucât aceste intervenții implică  participarea conștientă a subiectului și acțiunea lui voluntară, considerăm că rezultatele discutate prezintă relevanță în dezbaterea privitoare la liberul arbitru. Se evidențiază, totodată, importanța educației și a cunoașterii în plan social, precum și  necesitatea promovării unor prevenții și terapeutici participative, care să implice subiectul în creșterea calitativă a vieții și sănătății lui, prin mesaje care să sublinieze responsabilitatea fiecărei persoane pentru alegerile și acțiunile proprii și impactul pe care acestea îl au asupra vieții sale.

The plasticity of neural stem/progenitor cells allows a variety of different responses to many environmental cues. In the past decade, significant research has gone into understanding the regulation of neural stem/progenitor cell properties, because of their promise for cell replacement therapies in adult neurological diseases. Both endogenous and grafted neural stem/progenitor cells are known to have the ability to migrate long distances to lesioned sites after brain injury and differentiate into new neurons. Several chemokines and growth factors, including stromal cell-derived factor-1 and vascular endothelial growth factor, have been shown to stimulate the proliferation, differentiation, and migration of neural stem/progenitor cells, and investigators have now begun to identify the critical downstream effectors and signaling mechanisms that regulate these processes. Both our own lab and others have shown that the extracellular matrix and matrix remodeling factors play a critical role in directing cell differentiation and migration of adult neural stem/progenitor cells within injured sites. Identification of these and other molecular pathways involved in stem cell homing into ischemic areas is vital for the development of new treatments. To ensure the best functional recovery, regenerative therapy may require the application of a combination approach that includes cell replacement, trophic support, and neural protection. Here we review the current state of our knowledge about endogenous adult and exogenous neural stem/progenitor cells as potential therapeutic agents for central nervous system injuries.

The original definition of atypical antipsychotic drugs (APD) was drugs that are effective against positive symptoms in schizophrenia with no or little extrapyramidal symptoms (EPS). However, atypical APD have been reported to be more effective for cognitive dysfunction and negative symptoms in schizophrenia than typical APD, which expands the definition of 'atypicality'. This article provides a critical review of the pharmacology of atypical APD, especially from the viewpoint of receptor binding profiles and neurotransmitter regulations as well as neuroprotection and neurogenesis. A variety of serotonin (5-HT) receptors, such as 5-HT2A / 2C , 5-HT1A , 5-HT6 and 5-HT7 receptors, may contribute to the mechanisms of action of 'atypicality'. The dopaminergic modulations, including a low affinity for dopamine D2 receptors and a partial D2 receptor agonistic action, and glutamatergic regulations may also be involved in the pharmacological backgrounds of 'atypicality&#...