Premature infants exhibit neurodevelopmental delay and reduced growth of the cerebral cortex. However, the underlying mechanisms have remained elusive. Therefore, we hypothesized that neurogenesis in the ventricular and subventricular zones of the cerebral cortex would continue in the third trimester of pregnancy and that preterm birth would suppress neurogenesis. To test our hypotheses, we evaluated autopsy materials from human fetuses and preterm infants of 16–35 gestational weeks (gw). We noted that both cycling and noncycling Sox2+radial glial cells and Tbr2+intermediate progenitors were abundant in human preterm infants until 28 gw. However, their densities consistently decreased from 16 through 28 gw. To determine the effect of premature birth on neurogenesis, we used a rabbit model and compared preterm [embryonic day 29 (E29), 3 d old] and term (E32, <2 h old) pups at an equivalent postconceptional age. Glutamatergic neurogenesis was suppressed in preterm rabbits, as indicated by the reduced number of Tbr2+intermediate progenitors and the increased number of Sox2+radial glia. Additionally, hypoxia-inducible factor-1α, vascular endothelial growth factor, and erythropoietin were higher in term than preterm pups, reflecting the hypoxic intrauterine environment of just-born term pups. Proneural genes, including Pax6 and Neurogenin-1 and -2, were higher in preterm rabbit pups compared with term pups. Importantly, neurogenesis and associated factors were restored in preterm pups by treatment with dimethyloxallyl glycine, a hypoxia mimetic agent. Hence, glutamatergic neurogenesis continues in the premature infants, preterm birth suppresses neurogenesis, and hypoxia-mimetic agents might restore neurogenesis, enhance cortical growth, and improve neurodevelopmental outcome of premature infants.

The processes regulating cortical surface area expansion during development and evolution are unknown. We show that loss of function of all fibroblast growth factor receptors (FgfRs) expressed at the earliest stages of cortical development causes severe deficits in surface area growth by embryonic day 12.5 (E12.5) in the mouse. In FgfR mutants, accelerated production of neurons led to severe loss of radial progenitors and premature termination of neurogenesis. Nevertheless, these mutants showed remarkably little change in cortical layer structure. Birth-dating experiments indicated that a greater proportion of layer fates was generated during early neurogenic stages, revealing that FgfR activity normally slows the temporal progression of cortical layer fates. Electroporation of a dominant-negative FgfR at E11.5 increased cortical neurogenesis in normal mice—an effect that was blocked by simultaneous activation of the Notch pathway. Together with changes in the expression of Notch pathway genes in FgfR mutant embryos, these findings indicate that Notch lies downstream of FgfR signaling in the same pathway regulating cortical neurogenesis and begin to establish a mechanism for regulating cortical surface expansion.

Neurogenesis is not limited to the embryonic stage, but continually proceeds in the adult brain throughout life. Epigenetic mechanisms, including DNA methylation, histone modification and noncoding RNA, play important roles in neurogenesis. For decades, DNA methylation was thought to be a stable modification, except for demethylation in the early embryo. In recent years, DNA methylation has proved to be dynamic during development. In this review, we summarize the latest understanding about DNA methylation dynamics in neurogenesis, including the roles of different methylation forms (5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine), as well as their 'writers', 'readers' and interactions with histone modifications.

Huntington's disease (HD) is a neurodegenerative disorder caused by a tandem repeat expansion encoding a polyglutamine tract in the huntingtin protein. HD involves progressive psychiatric, cognitive, and motor symptoms, the selective pathogenesis of which remains to be mechanistically elucidated. There are a range of different brain regions, including the cerebral cortex and striatum, known to be affected in HD, with evidence for hippocampal dysfunction accumulating in recent years. In this review we will focus on hippocampal abnormalities, in particular, deficits of adult neurogenesis. We will discuss potential molecular mechanisms mediating disrupted hippocampal neurogenesis, and how this deficit of cellular plasticity may in turn contribute to specific cognitive and affective symptoms that are prominent in HD. The generation of transgenic animal models of HD has greatly facilitated our understanding of disease mechanisms at molecular, cellular, and systems levels. Transgenic HD mice have been found to show progressive behavioral changes, including affective, cognitive, and motor abnormalities. The discovery, in multiple transgenic lines of HD mice, that adult hippocampal neurogenesis and synaptic plasticity is disrupted, may help explain specific aspects of cognitive and affective dysfunction. Furthermore, these mouse models have provided insight into potential molecular mediators of adult neurogenesis deficits, such as disrupted serotonergic and neurotrophin signaling. Finally, a number of environmental and pharmacological interventions which are known to enhance adult hippocampal neurogenesis have been found to have beneficial affective and cognitive effects in mouse models, suggesting common molecular targets which may have therapeutic utility for HD and related diseases. Neural Plast Neural Plast 478 neuralplast NP Neural Plasticity 2090-5904 1687-5443 Wiley PMC3394391 PMC3394391.1 3394391 3394391 22830053 10.1155/2012/874387 1 Review Article Hippocampal Neurogenesis, Cognitive Deficits and Affective Disorder in Huntington's Disease Ransome Mark I. 1 * Renoir Thibault 1 Hannan Anthony J. 1 2 * 1 Florey Neuroscience Institutes, Melbourne Brain Centre, University of Melbourne, Melbourne, VIC 3010, Australia 2 Department of Anatomy and Cell Biology, University of Melbourne, Melbourne, VIC 3010, Australia *Mark I. Ransome: mark.ransome@florey.edu.au and *Anthony J. Hannan: anthony.hannan@florey.edu.au Academic Editor: Cara J. Embedded within the formulation and refinement of the Neuron Doctrine was born the concept of neuronal plasticity or structural modifiability of the brain [ 2 ]. Arguably, and perhaps unwittingly, the developing theory of neural plasticity was linked with functional roles in learning and memory. However, the ability of the brain to modify its connections was tempered by the overriding edict that the adult neuronal population was stable. In other words, production of new neurons—neurogenesis—was complete prior to brain maturation. Thus another basic tenet of the Neuron Doctrine was that the adult mammalian brain was devoid of ongoing neurogenesis. This view of adult neurogenesis pervaded neuroscience for a substantial portion of the twentieth century, holding sway in spite of early contradictory evidence [ 3 , 4 ]. With technical advancements and overwhelming evidence, adult neurogenesis in the mammalian brain became a widely accepted concept by the close of the twentieth century [ 5 ]. Addition of new neurons to established circuitry of the adult brain affords a novel form of neuronal plasticity beyond the Adult hippocampal neurogenesis (AHN) is a highly regulated multistep process involving proliferation of neuronal stem/precursor cells, neuronal differentiation and migration, and finally neuronal maturation and integration into the existing hippocampal circuitry [ 17 ]. A diversity of factors targets these regulatory steps to affect the net rate of AHN. A significant foundation for the neurogenesis hypothesis of depression arises from data that shows neurotransmitter systems involved in the development and treatment of depression also regulate levels of AHN [ 14 ]. Selective serotonin uptake inhibitors (SSRIs), such as fluoxetine (Prozac) and sertraline continue to be a core pharmacological intervention for major depressive disorder [ 23 , 24 ]. A significant mechanism of action of the antidepressant effects of SSRIs involves potentiation of serotonergic neurotransmission through inhibition of synaptic clearance. Reflecting the incidence of HD patient depression, depressive-like behavior manifests in premotor symptomatic R6/1 HD mice [ 21 , 25 ]. Early analysis of R6/1 HD mice showed a reduction in hippocampal stem/precursor cell proliferation leading to a net reduction in AHN [ 26 ]. Finally, a new study has revealed sexually dimorphic affective dysfunction and adult neurogenesis (neuronal maturation but not cell proliferation) deficits in the Hdh Q111 knock-in mouse model of HD [ 40 ]. Thus, for all of the HD mouse models investigated AHN is abnormal, suggesting that this is a robust effect of the HD gene mutation expressed in different contexts. Physical activity is advocated to maintain mental health including the prevention and amelioration of depression and anxiety [ 38 ]. Physical activity was one of the first physiological factors found to both increase AHN and improve hippocampal function in rodents [ 41 ]. Our endeavors to elucidate the role of AHN in the etiology of psychiatric illness have demonstrated that rates of proliferation, differentiation, and survival of adult hippocampal neurons are similar between male and female mice [ 58 ]. Furthermore, our current work on R6/1 HD mice shows no change between male and female hippocampal stem/precursors cell proliferation (Ransome and Hannan, submitted). This is reflected in YAC128 mice, in which impaired adult hippocampal neurogenesis manifests similarly in both males and females [ 39 ].

In the mammalian brain, new neurons continue to be generated throughout life in a process known as adult neurogenesis. The role of adult-generated neurons has been broadly studied across laboratories, and mounting evidence suggests a strong link to the HPA axis and concomitant malfunctions in patients diagnosed with mood disorders. Psychedelic compounds, such as phenethylamines, tryptamines, cannabinoids, and a variety of ever-growing chemical categories, have emerged as therapeutic options for neuropsychiatric disorders, while numerous reports link their effects to increased adult neurogenesis. In this systematic review, we examine studies assessing neurogenesis or neurogenesis-associated brain plasticity after psychedelic interventions and aim to provide a comprehensive picture of how this vast category of compounds regulates the generation of new neurons. We conducted a literature search on PubMed and Science Direct databases, considering all articles published until January 31, 2023, and selected articles containing both the terms "neurogenesis" and "psychedelics". We analyzed experimental studies using either in vivo or in vitro models, employing classical or atypical psychedelics at all ontogenetic windows, as well as human studies referring to neurogenesis-associated plasticity. Of a total of 205 articles, 68 met all the necessary conditions for further review. Our findings were divided into five main categories of psychedelics: CB1 agonists, NMDA antagonists, harmala alkaloids, tryptamines, and entactogens. We described the outcomes of neurogenesis assessments and investigated related results on the effects of psychedelics on brain plasticity and behavior within our sample. In summary, this review presents an extensive study into how different psychedelics may affect the birth of new neurons and other brain-related processes. Such knowledge may be valuable for future research on novel therapeutic strategies for neuropsychiatric disorders.

Abstract In the dentate gyrus of mammals, including humans, adult hippocampal neurogenesis lifelong generates one single type of excitatory neurons, new granule cell neurons, which contribute to the mossy fiber connection between the dentate gyrus and area CA3. Adult hippocampal neurogenesis originates from a unique radial glia-like stem cell population (type 1 cells) that became displaced from the ventricular wall during development and is found in the subgranular zone between the granule cell layer proper and the hilus. The stem cells give rise to intermediate progenitor cells (type 2), which are highly proliferative, and a late, less-proliferative neuroblast-like cell (type 3). After exit from the cell cycle the newborn neurons are selected for survival and go through a period of heightened synaptic plasticity and functional maturation. The chapter describes the development of new neurons in the adult dentate gyrus in detail, including the quiescent state of the type 1 cells and the late integration phase, when the cells become indistinguishable from the older granule cells. Regulation of adult hippocampal neurogenesis is covered in Chapter 9; the function of the new neurons in Chapter 10.

Stem cell-based therapies, particularly those involving neural stem cells (NSCs), offer great promise for the treatment of cerebral ischemia, a condition that includes ischemic stroke, cardiac arrest-induced global ischemia, and hypoxic-ischemic encephalopathy. Preclinical models demonstrate that NSC therapy can promote neuroregeneration, reduce inflammation, and improve functional recovery. However, translation into clinical application remains hindered by poor graft survival, limited integration, and adverse microenvironments. To overcome these barriers, multiple stem cell modification techniques have been developed, including metabolic glycoengineering, genetic modification, preconditioning, and biomaterial encapsulation. This chapter reviews the pathophysiology of cerebral ischemia, the mechanisms of NSC therapy, and advanced bioengineering strategies to enhance stem cell therapeutic efficacy across different ischemic models.

Neurogenesis was first discovered in songbirds that produce new neurons while learning songs. For mammals, new neurons also play an important role in learning: about 1000 new neurons develop in the hippocampus (a brain structure involved in learning and memory) each day. While most of the new neurons will die, researchers found that an increase in the number of surviving new neurons in the hippocampus correlated with how well rats learned a new task. Interestingly, both exercise and some antidepressant medications also promote neurogenesis in the hippocampus. Stress has the opposite effect. While neurogenesis is quite limited compared to regeneration in other tissues, research in this area may lead to new treatments for disorders such as Alzheimer’s, stroke, and epilepsy. How do scientists identify new neurons? A researcher can inject a compound called bromodeoxyuridine (BrdU) into the brain of an animal. While all cells will be exposed to BrdU, BrdU will only be incorporated into the DNA of newly generated cells that are in S phase.

Abstract Adult neurogenesis is very common across the animal kingdom but also highly variable between species. This chapter gives a thorough overview of what we know about neurogenesis in animals as diverse as flies, crickets, salamanders, amphibians, fish, birds, and many others. Most information is available about adult neurogenesis in mammals, especially mice and rats but also primate species, in which adult neurogenesis is more concentrated to specific neurogenic regions than in lower species. Adult neurogenesis in the subventricular zone/olfactory bulb is highly conserved across mammalian species but, with respect to the bulb, appears to be essentially absent in humans. Adult hippocampal neurogenesis is particular in that only mammals evolved a dentate gyrus. It is also conserved in humans, as demonstrated by a large number of studies and a great variety of methods, and it presumably contributes to hippocampal functions central to cognition. Besides all similarities, species differences are important and instructive as adult neurogenesis might provide a particular means of adaptation to habitats and species-dependent needs. The chapter thus also includes a section that reflects upon the evolution of adult neurogenesis.

Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). This occurs in all species of animals Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). This occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells (NECs), radial glial cells (RGCs), basal progenitors (BPs), intermediate neuronal precursors (INPs), subventricular zone astrocytes, and subgranular zone rad Du… Neurogenesis can be a complex process in some mammals. In rodents for example, neurons in the central nervous system arise from three types of neural stem and progenitor cells: neuroepithelial cells, radial glial cells and basal progenitors, which go through three main divisions: symmetric proliferative division; asymmetric neurogenic division; and symmetric neurogenic division. Out of all the three cell types, neuroepithelial cells that pass through neurogenic divisions have a much more extended cell cycle than those that go through proliferative divisions, such as the radial glial cells and basal progenitors. In the human, adult neurogenesis has been shown to occur at low levels compared with development, and in only three regions of the brain: the adult subventricular zone (SVZ) of the lateral ventricles, the amygdala and the dentate gyrus of the hippocampus. Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). This occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells (NECs), radial glial cells (RGCs), basal progenitors (BPs), intermediate neuronal precursors (INPs), subventricular zone astrocytes, and subgranular zone radial astrocytes, among others. Neurogenesis is most active during embryonic development and is responsible for producing all the various types of neurons of the organism, but it continues throughout adult life in a variety of organisms. Once born, neurons do not divide (see mitosis), and many will live the lifespan of the animal, except under extraordinary and usually pathogenic circumstances. During embryonic development, the mammalian central nervous system (CNS; brain and spinal cord) is derived from the neural tube, which contains NSCs that will later generate neurons. However, neurogenesis doesn't begin until a sufficient population of NSCs has been achieved. These early stem cells are called neuroepithelial cells (NEC)s, but soon take on a highly elongated radial morphology and are then known as radial glial cells (RGC)s. RGCs are the primary stem cells of the mammalian CNS, and reside in the embryonic ventricular zone, which lies adjacent to the central fluid-filled cavity (ventricular system) of the neural tube. Following RGC proliferation, neurogenesis involves a final cell division of the parent RGC, which produces one of two possible outcomes. First, this may generate a subclass of neuronal progenitors called intermediate neuronal precursors (INP)s, which will divide one or more times to produce neurons. Alternatively, daughter neurons may be produced directly. Neurons do not immediately form neural circuits through the growth of axons and dendrites. Instead, newborn neurons must first migrate long distances to their final destinations, maturing and finally generating neural circuitry. For example, neurons born in the ventricular zone migrate radially to the cortical plate, which is where neurons accumulate to form the cerebral cortex. Thus, the generation of neurons occurs in a specific tissue compartment or 'neurogenic niche' occupied by their parent stem cells. The rate of neurogenesis and the type of neuron generated (broadly, excitatory or inhibitory) are principally determined by molecular and genetic factors. These factors notably include the Notch signaling pathway, and many genes have been linked to Notch pathway regulation. The genes and mechanisms involved in regulating neurogenesis are the subject of intensive research in academic, pharmaceutical, and government settings worldwide. The amount of time required to generate all the neurons of the CNS varies widely across mammals, and brain neurogenesis is not always complete by the time of birth. For example, mice undergo cortical neurogenesis from about embryonic day (post-conceptional day) (E)11 to E17, and are born at about E19.5. Ferrets are born at E42, although their period of cortical neurogenesis does not end until a few days after birth. In contrast, neurogenesis in humans generally begins around gestational week (GW) 10 and ends around GW 25 with birth about GW 38–40. Neurogenesis can be a complex process in some mammals. In rodents for example, neurons in the central nervous system arise from three types of neural stem and progenitor cells: neuroepithelial cells, radial glial cells and basal progenitors, which go through three main divisions: symmetric proliferative division; asymmetric neurogenic division; and symmetric neurogenic division. Out of all the three cell types, neuroepithelial cells that pass through neurogenic divisions have a much more extended cell cycle than those that go through proliferative divisions, such as the radial glial cells and basal progenitors. In the human, adult neurogenesis has been shown to occur at low levels compared with development, and in only three regions of the brain: the adult subventricular zone (SVZ) of the lateral ventricles, the amygdala and the dentate gyrus of the hippocampus.

absence of major neurogenesis. However, Joseph Altman showed that cell division does occur in the brain which allowed potential for stem cell therapy for nerve Myelitis is inflammation of the spinal cord which can disrupt the normal responses from the brain to the rest of the body, and from the rest of the body to the brain. Inflammation in the spinal cord can cause the myelin and axon to be damaged resulting in symptoms such as paralysis and sensory loss. Myelitis is classified to several categories depending on the area or the cause of the lesion; howe Engineering endogenous repair: Currently, there exists a hydrogel based scaffold which acts as a channel to deliver nerve growth-enhancing substrates while providing structural support. These factors would promote nerve repairs to the target area. Hydrogels' macroporous properties would enable attachment of cells and enhance ion and nutrient exchange. In addition, hydrogels' biodegradability or bioresolvability would prevent the need for surgical removal of the hydrogel after drug delivery. It means that it would be dissolved naturally by the body's enzymatic reaction. Biochemical repair Neurotropic factor therapy and gene therapy Neurotropic growth factors regulate growth, survival, and plasticity of the axon. They benefit nerve regeneration after injury to the nervous system. They are a potent initiator of sensory axon growth and are up-regulated at the lesion site. The continuous delivery of neurotropic growth factor (NGF) would increase the nerve regeneration in the spinal cord. However, the excessive dosing of NGF often leads to undesired plasticity and sprouting of uninjured sensory nerves. Gene therapy would be able to increase the NGF efficacy by the controlled and sustained delivery in a site-specific manner. Stem cell-based therapies: The possibility for nerve regeneration after injury to the…

<h4>Background</h4>Allogeneic umbilical cord blood is regarded as a beneficial source of stem cells with varying therapeutic potential. On the other hand, cerebral palsy is one of the neurological conditions that are the primary contributor to early childhood disability. The aim of this systematic review was to harvest data from currently available sources to determine the safety and efficacy of treating cerebral palsy patients with stem cells obtained from allogeneic umbilical cords.<h4>Methods</h4>For this study, systematic searches of the databases PubMed, Scopus, Web of Science, Embase, ScienceDirect, and Google Scholar were conducted with no time Limit until November 2022. Duplicates were found and eliminated after entering the data from the chosen studies into the Endnote reference management program. The remaining studies were assessed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses phases and the inclusion and exclusion criteria (PRISMA). The search was performed using the keywords of Safety, Effectiveness, Stem Cells, Cerebral Palsy, and Umbilical and the (AND) and (OR) operators and their combinations were used to construct the search strategies.<h4>Results</h4>After several assessments and based on the inclusion and exclusion criteria, 31 of the remaining 58 studies were eliminated. The systematic review method included 7 final studies in the end. Based on the reviewed studies, it was reported that umbilical cord blood is currently one of the best sources of adult stem cells that contain cells with a wide range of therapeutic potential. These studies report that allogeneic umbilical cord blood has the potential to treat cerebral palsy and that concomitant administration of recombinant human erythropoietin (EPO), which has neurotrophic properties, may enhance the efficacy of umbilical cord blood. These studies state that pneumonia and irritability have been reported as complications of umbilical cord blood transfusion. These studies reported that administration of stem cells significantly improves motor function. The safety and efficacy of treating cerebral palsy patients with stem cells taken from an allogeneic umbilical cord were reported in all included investigations.<h4>Conclusion</h4>Cerebral palsy has negative consequences on patients' quality of life, many aspects of the treatment based on allogeneic umbilical cord stem cells remain unknown. Therefore, the optimal dose, the most suitable type of cell, cell identification, and the best administration route should be determined appropriately. The quality of life of patients with cerebral palsy may be negatively impacted, and many details of the allogeneic umbilical cord stem cell therapy are yet unknown. Consequently, it is important to discover the most suitable type of cell, the optimal dose, and the best delivery method.