Brain plasticity (Amsterdam, Netherlands)最新文献

Neural stem/progenitor cells (NSPCs) give rise to billions of cells during development and are critical for proper brain formation. The finding that NSPCs persist throughout adulthood has challenged the view that the brain has poor regenerative abilities and raised hope for stem cell-based regenerative therapies. For decades there has been a strong movement towards understanding the requirements of NSPCs and their regulation, resulting in the discovery of many transcription factors and signaling pathways that can influence NSPC behavior and neurogenesis. However, the role of metabolism for NSPC regulation has only gained attention recently. Lipid metabolism in particular has been shown to influence proliferation and neurogenesis, offering exciting new possible mechanisms of NSPC regulation, as lipids are not only the building blocks of membranes, but can also act as alternative energy sources and signaling entities. Here I review the recent literature examining the role of lipid metabolism for NSPC regulation and neurogenesis.

Within the brain, the physiological and pathological functions of autophagy in development and throughout the lifespan are being elucidated. This review summarizes recent in vitro and in vivo results that are defining the role of autophagy-related genes during the process of adult neurogenesis. We also discuss the need for future experiments to determine the molecular mechanism and functional significance of autophagy in the different neural stem cell populations and throughout the stages of adult neurogenesis.

Hippocampal neural stem/progenitor cells (NSPCs) proliferate and differentiate to generate new neurons across the life span of most mammals, including humans. This process takes place within a characteristic local microenvironment where NSPCs interact with a variety of other cell types and encounter systemic regulatory factors. Within this microenvironment, cell intrinsic gene expression programs are modulated by cell extrinsic signals through complex interactions, in many cases involving short non-coding RNA molecules, such as miRNAs. Here we review the regulation of gene expression in NSPCs by miRNAs and its possible implications for epilepsy, which has been linked to alterations in adult hippocampal neurogenesis.

Most genes required for mammalian development are expressed from both maternally and paternally inherited chromosomal homologues. However, there are a small number of genes known as "imprinted genes" that only express a single allele from one parent, which is repressed on the gene from the other parent. Imprinted genes are dependent on epigenetic mechanisms such as DNA methylation and post-translational modifications of the DNA-associated histone proteins to establish and maintain their parental identity. In the brain, multiple transcripts have been identified which show parental origin-specific expression biases. However, the mechanistic relationship with canonical imprinting is unknown. Recent studies on the postnatal neurogenic niches raise many intriguing questions concerning the role of genomic imprinting and gene dosage during postnatal neurogenesis, including how imprinted genes operate in concert with signalling cues to contribute to newborn neurons' formation during adulthood. Here we have gathered the current knowledge on the imprinting process in the neurogenic niches. We also review the phenotypes associated with genetic mutations at particular imprinted loci in order to consider the impact of imprinted genes in the maintenance and/or differentiation of the neural stem cell pool in vivo and during brain tumour formation.

The role of DNA methylation in brain development is an intense area of research because the brain has particularly high levels of CpG and mutations in many of the proteins involved in the establishment, maintenance, interpretation, and removal of DNA methylation impact brain development and/or function. These include DNA methyltransferase (DNMT), Ten-Eleven Translocation (TET), and Methyl-CpG binding proteins (MBPs). Recent advances in sequencing breadth and depth as well the detection of different forms of methylation have greatly expanded our understanding of the diversity of DNA methylation in the brain. The contributions of DNA methylation and associated proteins to embryonic and adult neurogenesis will be examined. Particular attention will be given to the impact on adult hippocampal neurogenesis (AHN), which is a key mechanism contributing to brain plasticity, learning, memory and mood regulation. DNA methylation influences multiple aspects of neurogenesis from stem cell maintenance and proliferation, fate specification, neuronal differentiation and maturation, and synaptogenesis. In addition, DNA methylation during neurogenesis has been shown to be responsive to many extrinsic signals, both under normal conditions and during disease and injury. Finally, crosstalk between DNA methylation, Methyl-DNA binding domain (MBD) proteins such as MeCP2 and MBD1 and histone modifying complexes is used as an example to illustrate the extensive interconnection between these epigenetic regulatory systems.

The life-long generation of new neurons from radial glia-like neural stem cells (NSCs) is achieved through a stereotypic developmental sequence that requires precise regulatory mechanisms to prevent exhaustion or uncontrolled growth of the stem cell pool. Cellular metabolism is the new kid on the block of adult neurogenesis research and the identity of stage-specific metabolic programs and their impact on neurogenesis turns out to be an emerging research topic in the field. Mitochondrial metabolism is best known for energy production but it contains a great deal more. Mitochondria are key players in a variety of cellular processes including ATP synthesis through functional coupling of the electron transport chain and oxidative phosphorylation, recycling of hydrogen carriers, biosynthesis of cellular building blocks, and generation of reactive oxygen species that can modulate signaling pathways in a redox-dependent fashion. In this review, I will discuss recent findings describing stage-specific modulations of mitochondrial metabolism within the adult NSC lineage, emphasizing its importance for NSC self-renewal, proliferation of neural stem and progenitor cells (NSPCs), cell fate decisions, and differentiation and maturation of newborn neurons. I will furthermore summarize the important role of mitochondrial dysfunction in tissue regeneration and ageing, suggesting it as a potential therapeutic target for regenerative medicine practice.

Adult neural stem cells are generated at embryonic stages by entering a quiescent state that allows their retention into adulthood and thereby maintenance of life-long brain homeostasis. Thus, a tight balance between the quiescence and activation state is instrumental to meet the brain demands for a specific cell type at the correct numbers, at a given time and position. Protein synthesis is the most energy-consuming process within the cell and, not surprisingly, it occurs at low rates in quiescent stem cells. This way quiescent cells adjust to energy constraints and avoid their premature depletion. Stem cell activation is characterized by upregulation of protein synthesis followed by cell division and differentiation. The role of such upregulation as causative or rather a consequence of the activation remains elusive. Here we summarize recent findings connecting stem cell activation to the regulation of protein synthesis, particularly focusing on embryonic and adult neural stem cells of the ventricular zone.

A significant body of work has investigated the effects of acute exercise, defined as a single bout of physical activity, on mood and cognitive functions in humans. Several excellent recent reviews have summarized these findings; however, the neurobiological basis of these results has received less attention. In this review, we will first briefly summarize the cognitive and behavioral changes that occur with acute exercise in humans. We will then review the results from both human and animal model studies documenting the wide range of neurophysiological and neurochemical alterations that occur after a single bout of exercise. Finally, we will discuss the strengths, weaknesses, and missing elements in the current literature, as well as offer an acute exercise standardization protocol and provide possible goals for future research.