Research

18 pages, 23513 KiB

Open AccessArticle

Functional Activation of Newborn Neurons Following Alcohol-Induced Reactive Neurogenesis

by Natalie N. Nawarawong, Chelsea G. Nickell, Deann M. Hopkins, James R. Pauly and Kimberly Nixon

Brain Sci. 2021, 11(4), 499; https://doi.org/10.3390/brainsci11040499 - 15 Apr 2021

Cited by 7 | Viewed by 3256

Abstinence after alcohol dependence leads to structural and functional recovery in many regions of the brain, especially the hippocampus. Significant increases in neural stem cell (NSC) proliferation and subsequent “reactive neurogenesis” coincides with structural recovery in hippocampal dentate gyrus (DG). However, whether these [...] Read more.

Abstinence after alcohol dependence leads to structural and functional recovery in many regions of the brain, especially the hippocampus. Significant increases in neural stem cell (NSC) proliferation and subsequent “reactive neurogenesis” coincides with structural recovery in hippocampal dentate gyrus (DG). However, whether these reactively born neurons are integrated appropriately into neural circuits remains unknown. Therefore, adult male rats were exposed to a binge model of alcohol dependence. On day 7 of abstinence, the peak of reactive NSC proliferation, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells. After six weeks, rats underwent Morris Water Maze (MWM) training then were sacrificed ninety minutes after the final training session. Using fluorescent immunohistochemistry for c-Fos (neuronal activation), BrdU, and Neuronal Nuclei (NeuN), we investigated whether neurons born during reactive neurogenesis were incorporated into a newly learned MWM neuronal ensemble. Prior alcohol exposure increased the number of BrdU+ cells and newborn neurons (BrdU+/NeuN+ cells) in the DG versus controls. However, prior ethanol exposure had no significant impact on MWM-induced c-Fos expression. Despite increased BrdU+ neurons, no difference in the number of activated newborn neurons (BrdU+/c-Fos+/NeuN+) was observed. These data suggest that neurons born during alcohol-induced reactive neurogenesis are functionally integrated into hippocampal circuitry. Full article

(This article belongs to the Special Issue Neurogenesis and Gliogenesis in Health and Disease)

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14 pages, 3808 KiB

Open AccessArticle

Generation of the Human Pluripotent Stem-Cell-Derived Astrocyte Model with Forebrain Identity

by Ulla-Kaisa Peteri, Juho Pitkonen, Kagistia Hana Utami, Jere Paavola, Laurent Roybon, Mahmoud A. Pouladi and Maija L. Castrén

Brain Sci. 2021, 11(2), 209; https://doi.org/10.3390/brainsci11020209 - 09 Feb 2021

Cited by 9 | Viewed by 3620

Abstract

Astrocytes form functionally and morphologically distinct populations of cells with brain-region-specific properties. Human pluripotent stem cells (hPSCs) offer possibilities to generate astroglia for studies investigating mechanisms governing the emergence of astrocytic diversity. We established a method to generate human astrocytes from hPSCs with [...] Read more.

Astrocytes form functionally and morphologically distinct populations of cells with brain-region-specific properties. Human pluripotent stem cells (hPSCs) offer possibilities to generate astroglia for studies investigating mechanisms governing the emergence of astrocytic diversity. We established a method to generate human astrocytes from hPSCs with forebrain patterning and final specification with ciliary neurotrophic factor (CNTF). Transcriptome profiling and gene enrichment analysis monitored the sequential expression of genes determining astrocyte differentiation and confirmed activation of forebrain differentiation pathways at Day 30 (D30) and D60 of differentiation in vitro. More than 90% of astrocytes aged D95 in vitro co-expressed the astrocytic markers glial fibrillary acidic protein (GFAP) and S100β. Intracellular calcium responses to ATP indicated differentiation of the functional astrocyte population with constitutive monocyte chemoattractant protein-1 (MCP-1/CCL2) and tissue inhibitor of metalloproteinases-2 (TIMP-2) expression. The method was reproducible across several hPSC lines, and the data demonstrated the usefulness of forebrain astrocyte modeling in research investigating forebrain pathology. Full article

(This article belongs to the Special Issue Neurogenesis and Gliogenesis in Health and Disease)

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14 pages, 5087 KiB

Open AccessArticle

Differential Timing and Coordination of Neurogenesis and Astrogenesis in Developing Mouse Hippocampal Subregions

by Allison M. Bond, Daniel A. Berg, Stephanie Lee, Alan S. Garcia-Epelboim, Vijay S. Adusumilli, Guo-li Ming and Hongjun Song

Brain Sci. 2020, 10(12), 909; https://doi.org/10.3390/brainsci10120909 - 26 Nov 2020

Cited by 24 | Viewed by 3792

Abstract

Neocortical development has been extensively studied and therefore is the basis of our understanding of mammalian brain development. One fundamental principle of neocortical development is that neurogenesis and gliogenesis are temporally segregated processes. However, it is unclear how neurogenesis and gliogenesis are coordinated [...] Read more.

Neocortical development has been extensively studied and therefore is the basis of our understanding of mammalian brain development. One fundamental principle of neocortical development is that neurogenesis and gliogenesis are temporally segregated processes. However, it is unclear how neurogenesis and gliogenesis are coordinated in non-neocortical regions of the cerebral cortex, such as the hippocampus, also known as the archicortex. Here, we show that the timing of neurogenesis and astrogenesis in the Cornu Ammonis (CA) 1 and CA3 regions of mouse hippocampus mirrors that of the neocortex; neurogenesis occurs embryonically, followed by astrogenesis during early postnatal development. In contrast, we find that neurogenesis in the dentate gyrus begins embryonically but is a protracted process which peaks neonatally and continues at low levels postnatally. As a result, astrogenesis, which occurs during early postnatal development, overlaps with the process of neurogenesis in the dentate gyrus. During all stages, neurogenesis overwhelms astrogenesis in the dentate gyrus. In addition, we find that the timing of peak astrogenesis varies by hippocampal subregion. Together, our results show differential timing and coordination of neurogenesis and astrogenesis in developing mouse hippocampal subregions and suggest that neurogenesis and gliogenesis occur simultaneously during dentate gyrus development, challenging the conventional principle that neurogenesis and gliogenesis are temporally separated processes. Full article

(This article belongs to the Special Issue Neurogenesis and Gliogenesis in Health and Disease)

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20 pages, 3195 KiB

Open AccessFeature PaperArticle

Histone Lysine Demethylase JMJD2D/KDM4D and Family Members Mediate Effects of Chronic Social Defeat Stress on Mouse Hippocampal Neurogenesis and Mood Disorders

by Swati Maitra, Nitin Khandelwal, Scherazad Kootar, Pooja Sant, Salil S. Pathak, Sujatha Reddy, Annapoorna P. K., Upadhyayula Suryanarayana Murty, Sumana Chakravarty and Arvind Kumar

Brain Sci. 2020, 10(11), 833; https://doi.org/10.3390/brainsci10110833 - 09 Nov 2020

Cited by 8 | Viewed by 3515

Abstract

Depression, anxiety and related mood disorders are major psychiatric illnesses worldwide, and chronic stress appears to be one of the primary underlying causes. Therapeutics to treat these debilitating disorders without a relapse are limited due to the incomplete molecular understanding of their etiopathology. [...] Read more.

Depression, anxiety and related mood disorders are major psychiatric illnesses worldwide, and chronic stress appears to be one of the primary underlying causes. Therapeutics to treat these debilitating disorders without a relapse are limited due to the incomplete molecular understanding of their etiopathology. In addition to the well-studied genetic component, research in the past two decades has implicated diverse epigenetic mechanisms in mediating the negative effects of chronic stressful events on neural circuits. This includes the cognitive circuitry, where the dynamic hippocampal dentate gyrus (DG) neurogenesis gets affected in depression and related affective disorders. Most of these epigenetic studies have focused on the impact of acetylation/deacetylation and methylation of several histone lysine residues on neural gene expression. However, there is a dearth of investigation into the role of demethylation of these lysine residues in chronic stress-induced changes in neurogenesis that results in altered behaviour. Here, using the chronic social defeat stress (CSDS) paradigm to induce depression and anxiety in C57BL/6 mice and ex vivo DG neural stem/progenitor cell (NSCs/NPCs) culture we show the role of the members of the JMJD2/KDM4 family of histone lysine demethylases (KDMs) in mediating stress-induced changes in DG neurogenesis and mood disorders. The study suggests a critical role of JMJD2D in DG neurogenesis. Altered enrichment of JMJD2D on the promoters of Id2 (inhibitor of differentiation 2) and Sox2 (SRY-Box Transcription Factor 2) was observed during proliferation and differentiation of NSCs/NPCs obtained from the DG. This would affect the demethylation of repressive epigenetic mark H3K9, thus activating or repressing these and possibly other genes involved in regulating proliferation and differentiation of DG NSCs/NPCs. Treatment of the NSCs/NPCs culture with Dimethyloxallyl Glycine (DMOG), an inhibitor of JMJDs, led to attenuation in their proliferation capacity. Additionally, systemic administration of DMOG in mice for 10 days induced depression-like and anxiety-like phenotype without any stress exposure. Full article

(This article belongs to the Special Issue Neurogenesis and Gliogenesis in Health and Disease)

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Review

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22 pages, 434 KiB

Open AccessReview

Glial PAMPering and DAMPening of Adult Hippocampal Neurogenesis

by Luke Parkitny and Mirjana Maletic-Savatic

Brain Sci. 2021, 11(10), 1299; https://doi.org/10.3390/brainsci11101299 - 29 Sep 2021

Cited by 3 | Viewed by 2354

Abstract

Adult neurogenesis represents a mature brain’s capacity to integrate newly generated neurons into functional circuits. Impairment of neurogenesis contributes to the pathophysiology of various mood and cognitive disorders such as depression and Alzheimer’s Disease. The hippocampal neurogenic niche hosts neural progenitors, glia, and [...] Read more.

Adult neurogenesis represents a mature brain’s capacity to integrate newly generated neurons into functional circuits. Impairment of neurogenesis contributes to the pathophysiology of various mood and cognitive disorders such as depression and Alzheimer’s Disease. The hippocampal neurogenic niche hosts neural progenitors, glia, and vasculature, which all respond to intrinsic and environmental cues, helping determine their current state and ultimate fate. In this article we focus on the major immune communication pathways and mechanisms through which glial cells sense, interact with, and modulate the neurogenic niche. We pay particular attention to those related to the sensing of and response to innate immune danger signals. Receptors for danger signals were first discovered as a critical component of the innate immune system response to pathogens but are now also recognized to play a crucial role in modulating non-pathogenic sterile inflammation. In the neurogenic niche, viable, stressed, apoptotic, and dying cells can activate danger responses in neuroimmune cells, resulting in neuroprotection or neurotoxicity. Through these mechanisms glial cells can influence hippocampal stem cell fate, survival, neuronal maturation, and integration. Depending on the context, such responses may be appropriate and on-target, as in the case of learning-associated synaptic pruning, or excessive and off-target, as in neurodegenerative disorders. Full article

(This article belongs to the Special Issue Neurogenesis and Gliogenesis in Health and Disease)

15 pages, 1111 KiB

Open AccessFeature PaperReview

Plasticity in the Hippocampus, Neurogenesis and Drugs of Abuse

by Yosef Avchalumov and Chitra D. Mandyam

Brain Sci. 2021, 11(3), 404; https://doi.org/10.3390/brainsci11030404 - 22 Mar 2021

Cited by 21 | Viewed by 5898

Abstract

Synaptic plasticity in the hippocampus assists with consolidation and storage of long-lasting memories. Decades of research has provided substantial information on the cellular and molecular mechanisms underlying synaptic plasticity in the hippocampus, and this review discusses these mechanisms in brief. Addiction is a [...] Read more.

Synaptic plasticity in the hippocampus assists with consolidation and storage of long-lasting memories. Decades of research has provided substantial information on the cellular and molecular mechanisms underlying synaptic plasticity in the hippocampus, and this review discusses these mechanisms in brief. Addiction is a chronic relapsing disorder with loss of control over drug taking and drug seeking that is caused by long-lasting memories of drug experience. Relapse to drug use is caused by exposure to context and cues associated with the drug experience, and is a major clinical problem that contributes to the persistence of addiction. This review also briefly discusses some evidence that drugs of abuse alter plasticity in the hippocampus, and that development of novel treatment strategies that reverse or prevent drug-induced synaptic alterations in the hippocampus may reduce relapse behaviors associated with addiction. Full article

(This article belongs to the Special Issue Neurogenesis and Gliogenesis in Health and Disease)

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Jump to: Research, Review

1 pages, 157 KiB

Open AccessErratum

Erratum: Lee, J.G., et al. The Neuroprotective Effects of Melatonin: Possible Role in the Pathophysiology of Neuropsychiatric Disease. Brain Sciences 2019, 9(10), 285

by Jung Goo Lee, Young Sup Woo, Sung Woo Park, Dae-Hyun Seog, Mi Kyoung Seo and Won-Myong Bahk

Brain Sci. 2019, 9(12), 341; https://doi.org/10.3390/brainsci9120341 - 25 Nov 2019

Cited by 4 | Viewed by 1949

Abstract

The authors wish to make an erratum to the published version of their paper [...] Full article

(This article belongs to the Special Issue Neurogenesis and Gliogenesis in Health and Disease)

12 pages, 1260 KiB

Open AccessPerspective

The Neuroprotective Effects of Melatonin: Possible Role in the Pathophysiology of Neuropsychiatric Disease

by Jung Goo Lee, Young Sup Woo, Sung Woo Park, Dae-Hyun Seog, Mi Kyoung Seo and Won-Myong Bahk

Brain Sci. 2019, 9(10), 285; https://doi.org/10.3390/brainsci9100285 - 21 Oct 2019

Cited by 37 | Viewed by 6700

Abstract

Melatonin is a hormone that is secreted by the pineal gland. To date, melatonin is known to regulate the sleep cycle by controlling the circadian rhythm. However, recent advances in neuroscience and molecular biology have led to the discovery of new actions and [...] Read more.

Melatonin is a hormone that is secreted by the pineal gland. To date, melatonin is known to regulate the sleep cycle by controlling the circadian rhythm. However, recent advances in neuroscience and molecular biology have led to the discovery of new actions and effects of melatonin. In recent studies, melatonin was shown to have antioxidant activity and, possibly, to affect the development of Alzheimer’s disease (AD). In addition, melatonin has neuroprotective effects and affects neuroplasticity, thus indicating potential antidepressant properties. In the present review, the new functions of melatonin are summarized and a therapeutic target for the development of new drugs based on the mechanism of action of melatonin is proposed. Full article

(This article belongs to the Special Issue Neurogenesis and Gliogenesis in Health and Disease)

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