There is increasing evidence that glioblastoma, a highly aggressive brain tumour, originates from a neural stem cell (NSC) located in the subventricular zone (SVZ) of the lateral cerebral ventricle. Using the most advanced in vivo imaging techniques, Gengatharan and colleagues recently identified a day/night difference in the adult SVZ-NSC division. They reported that the circadian melatonin rhythm and its receptor control the day/night difference in NSC division with high mitotic activity during the day and low activity at night. Expression of melatonin and its receptor diminishes during ageing, which eliminates the regulatory effect of melatonin on NSC mitosis. Moreover, the circadian melatonin rhythm is dampened by light-at-night with the potential of altering the circadian mitotic cycle of NSC in the SVZ. Also, men with a lower melatonin amplitude than women exhibit a 60% higher rate of glioblastoma incidence. Given that ageing contributes significantly to glioblastoma initiation and progression, we suggest that the decline in circadian melatonin synthesis and release as well as its receptors in the SVZ, which also diminish with an ageing act in concert with other factors to facilitate glioblastoma initiation and growth.

Astronauts who spend significant time in space may experience intracranial hypertension (pressure inside the skull), which often does not normalize upon return to Earth. This type of intracranial pressure can cause vision problems, headaches, glaucoma, and other serious health problems, making it a significant obstacle to long-duration space exploration missions. NASA is hoping that a better understanding of how central nervous system stem cells divide in microgravity will help lead to ways to protect astronauts from problems with intracranial pressure and to design adequate preventive measures. These studies examine cell growth and division of neural stem cells that experienced microgravity on the International Space Station and were returned to normal gravity prior to live-cell imaging studies to determine cell changes.

Three areas in the brain continuously generate new neurons throughout life: the subventricular zone lining the lateral ventricles, the dentate gyrus in the hippocampus and the median eminence in the hypothalamus. These areas harbour neural stem cells, which contribute to neural repair by generating daughter cells that then become functional neurons or glia. Impaired neurogenesis leads to detrimental consequences, such as depression, decline of cognitive abilities and obesity. Adult neurogenesis is a versatile process that can be modulated either positively or negatively by many effectors, external or endogenous. Diet can modify neurogenesis both ways, either directly by ways of food-borne molecules, or possibly by the modifications induced on gut microbiota composition. It is therefore critical to define dietary strategies optimal for the maintenance of the stem cell pools.

We compared the characteristics of neural cells derived from induced pluripotent stem (iPS) cells from a patient with multiple sclerosis versus neurally differentiated control iPS cells of a healthy individual. The iPS cells were differentiated toward the oligodendrocyte lineage using a four-step protocol established for the differentiation of embryonic stem cells. The resulting cell population was immunostained on day 112 of differentiation for the presence of oligodendrocytes and analyzed by transmission electron microscopy (TEM). Both patient and control samples resembled a mixed population of neural cells rather than oligodendroglia of high purity, including neural stem cell-like cells and possibly oligodendrocytes demonstrable by TEM.

Toxoplasma gondii is a major cause of congenital brain disease; however, the underlying mechanism of neuropathogenesis in brain toxoplasmosis remains elusive. To explore the role of T. gondii in the development of neural stem cells (NSCs), NSCs were isolated from GD14 embryos of ICR mice and were co-cultured with tachyzoites of T. gondii RH strain. We found that apoptosis levels of the NSCs co-cultured with 1×106 RH tachyzoites for 24 and 48 h significantly increased in a dose-dependent manner, as compared with the control. Western blotting analysis displayed that the protein level of C/EBP homologous protein (CHOP) was up-regulated, and caspase-12 and c-Jun N-terminal kinase (JNK) were activated in the NSCs co-cultured with the parasites. Pretreatment with endoplasmic reticulum stress (ERS) inhibitor (TUDCA) and caspase-12 inhibitor (Z-ATAD-FMK) inhibited the expression or activation of the key molecules involved in the ERS-mediated apoptotic pathway, and subsequently decreased the apoptosis levels of the NSCs induced by the T. gondii. The findings here highlight that T. gondii induced apoptosis of the NSCs through the ERS signal pathway via activation of CHOP, caspase-12 and JNK, which may constitute a potential molecular mechanism responsible for the cognitive disturbance in neurological disorders of T. gondii.

The process of neurogenesis and formation of neural stem cells is reported in human neurospheres (NS) and embryoid bodies (EB) derived from human embryonic stem cells, in vitro, and compared with neural tissue formed in human ectopic embryos in week 4 (stage 9), developed in vivo. This morphological study was done using digital imaging by light microscopy and routine transmission electron microscopy. Both NS and EB form neural rosettes from the surface epithelium much like the process of neural tube formation from ectoderm in the embryo. The rosette is the developmental signature of neuroprogenitors in cultures of differentiating embryonic stem cells and is a radial arrangement of columnar cells that express many of the proteins expressed in neuroepithelial cells in the neural tube. The NS produce all of the major classes of progeny of the neural tube, some of which have been documented here. Specific neural markers expressed in the NS and the clinical implications of this study in cell therapy are also discussed.

Gene expression changes during cell differentiation are thought to be coordinated by histone modifications, but still little is known about the role of specific histone deacetylases (HDACs) in cell fate decisions in vivo. Here we demonstrate that the catalytic function of HDAC2 is required in adult, but not embryonic neurogenesis. While brain development and adult stem cell fate were normal upon conditional deletion of HDAC2 or in mice lacking the catalytic activity of HDAC2, neurons derived from both zones of adult neurogenesis die at a specific maturation stage. This phenotype is correlated with an increase in proliferation and the aberrant maintenance of proteins normally expressed only in progenitors, such as Sox2, also into some differentiating neurons, suggesting that HDAC2 is critically required to silence progenitor transcripts during neuronal differentiation of adult generated neurons. This cell-autonomous function of HDAC2 exclusively in adult neurogenesis reveals clear differences in the molecular mechanisms regulating neurogenesis during development and in adulthood.

The increasing appreciation of structural plasticity, namely the capacity of the nervous system to alter not only its function but also its constitution in response to changing conditions, indicates a profound transformation in the scientific comprehension of the human brain. The research on adult neurogenesis, i.e. on the de novo formation of neurons in the mature brain, has been chosen as a circumscribed field to study the controversies that accompany the transition from the concept of a stable to that of a structurally plastic mammalian brain. Building on the concepts of thought style and thought collective developed by Ludwik Fleck, this article investigates the ways in which neurogenesis in the adult brain has changed from being negated to being accepted and highly valued, and consequently has become the focus of a novel research field. This analysis covers a period from the second half of the twentieth century up to the present. The development of research on adult neurogenesis has been shaped by two opposing views: the understanding of a particularly immutable and thus specifically human brain on the one hand, and a plastic brain which remains malleable during the entire adult life, on the other hand. This plastic human brain has created new space for the articulation of the ‘therapeutic promise’, since it lends itself much more readily to therapeutic intervention than a stable brain: the article argues this to be decisive in promoting the transformation of thought style within the neurosciences.

One of the most challenging issues in developmental biology is to understand how cell diversity is generated. The Drosophila nervous system provides a model of choice for unraveling this process. First, many neural stem cells and lineages have been identified. Second, major molecular pathways involved in neural development and associated mutations have been characterized extensively in recent years. In this review, we focus on the cellular and molecular mechanisms underlying the generation of glia. This cell population relies on the expression of gcm fate determinant, which is necessary and sufficient to induce glial differentiation. We also discuss the recently identified role of gcm genes in Drosophila melanogaster and vertebrate neurogenesis. Finally, we will consider the Gcm pathway in the context of neural stem cell differentiation.

Neurogenesis, the generation of new neurons from neural precursor cells (NPCs), is a multi-step process that includes the proliferation of NPCs, fate determination, migration, and neuronal maturation. Neurogenesis is regulated by several extrinsic factors, such as enriched environment, physical exercise, hormones and stress, many of which also induce the expression of neurotrophins. In this review, we summarize studies on the role of neurotrophins in neurogenesis during development and in adults. We discuss the functional significance of neurogenesis in learning and memory, and how neurotrophins regulate this process. In this context, we describe recent experiments linking adult neurogenesis to long-term synaptic plasticity in the hippocampal dentate gyrus. Further study of the relationship between neurotrophins, adult neurogenesis and dentate synaptic plasticity might provide new insights into the mechanisms by which gene–environment interactions control cognition and brain plasticity.