It is crucial for future research to continue to investigate the functional role of adult neurogenesis in the normal human brain as well as alterations in neurodegenerative diseases

It is crucial for future research to continue to investigate the functional role of adult neurogenesis in the normal human brain as well as alterations in neurodegenerative diseases. stem cell niche. Vasculature, immune/support cell populations (microglia/astrocytes), adhesion molecules, growth factors, and the extracellular Moxalactam Sodium matrix also provide a homing environment for neural stem cells. Epigenetic changes during hippocampal neurogenesis also impact memory and learning. Some genetic variations in neurogenesis related genes may play important functions in the alteration of neural stem cells differentiation into new given birth to neurons during adult neurogenesis, with important therapeutic implications. In this review, we discuss mechanisms of and interactions between these modulators of adult neurogenesis, as well as implications for neurodegenerative disease and current therapeutic research. tailless gene (Tlx or NR2E1) and manipulate NSC self-renewal and proliferation [Sun et al., 2007]. Other epigenetic mechanisms involve non-coding RNAs such as microRNAs. MicroRNAs such as Let-7b, miR-9, miR-34a, and miR-184 regulate proliferation of NSCs and neuronal differentiation. MiR-137 and miR-132 also regulate synaptogenesis and the neuronal network, while miR-34a and miR-125b regulate dendritogenesis and spine morphology [Schouten et al., 2012; Volvert et al., 2012]. All of these epigenetic mechanisms highlight the importance of looking beyond the genome to understand the biological underpinnings of neurogenesis, which will be crucial to advance the state of research in therapeutic efforts to address neurogenesis in neurodegenerative disease. Epigenetic changes during neurogenesis have an important impact on memory and learning, and can play significant functions in neuropsychiatric disorders as well such as depression and schizophrenia [Sharma, 2005; Renthal et al., 2007; Hsieh and Eisch, 2010]. Role of Genetic Variation in Adult Neurogenesis Many gene expression level changes have been observed during adult neurogenesis, as presented in the previous sections; these changes affect NSC and progenitor proliferation, maintenance in the adult neurogenic niche, and differentiation into mature neurons. Although most of the studies focused on the alteration of gene expression during adult neurogenesis, some studies showed that genetic variations in adult neurogenesis-related genes affect hippocampal structure Moxalactam Sodium and memory impairment. For instance, the REST gene, a known transcriptional repressor, negatively regulates neuronal differentiation during neurogenesis, and nonsynonymous variation in this gene is usually associated with less hippocampal loss and greater cortical thickness in individuals who carry at least one minor allele [Lu et al., 2014; Nho et al., 2015; Thiel et al., 2015]. Another important gene related to adult neurogenesis is usually G-coupled protein receptor adenosine receptor A2A (ADORA2A) which plays a role in neurite growth. Alteration Moxalactam Sodium of the expression level of ADORA2A during adult neurogenesis affected neuronal differentiation, migration and maturation of new neurons [Sun et al., 2010; Shetty et al., 2013]. Variants in the ADORA2A gene differentially influence the transfer of information into working memory in homozygous rare genotype groups due to alteration of glutamergic neural transmission [Ferre et al., 2011; Beste et al., 2012]. Moreover, it has been shown that an ADORA2A antagonist reduced cognitive decline and resulted in a protective effect on memory formation in Parkinsons disease, Huntingtons disease, and Alzheimers disease models. [Chen, 2014; Rieck et al., 2015]. An additional Schizophrenia susceptibility gene, DISC-1, regulates neuronal integration of new neurons from neural progenitors into the adult brain and promotes structural plasticity [Duan et al., 2007). DISC-1 missense variation leads to a reduction of the proliferation of progenitor cells, which alters the balance between quiescent and proliferative neural stem cells in a transgenic mouse model Moxalactam Sodium [Chandran et al., 2014]. A missense mutation in the DISC-1 gene is related to alteration of the hippocampal structure by reducing gray matter volume and increases the risk for schizophrenia [Callicott et al., 2005]. As previously discussed, BDNF plays an important role in neural progenitor cell proliferation, differentiation and survival; additionally, overexpression of BDNF enhances adult neurogenesis by increasing dendritic spine density on granule cells. BDNF polymorphism Val66Met modulates integration of neurons in vivo and regulates episodic memory and hippocampal physiological activation in humans [Egan et al., 2003; McDole et al., 2015]. Moreover, genetic variation in BDNF associated with hippocampal atrophy and cognitive decline have been identified using neuroimaging-genetics methods [Honea et al., 2013]. Pro-inflammatory cytokine IL-6 plays an important role in the formation of new neurons and glial cells from Nr2f1 neural progenitor cells during adult neurogenesis, and IL-6 variations have been associated with AD, multiple sclerosis, and severe traumatic brain injury [Schmidt et al., 2003; He et al., 2010; Dalla Libera et al., 2011; Erta et al.,.

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