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Regulation and Function of Adult Neurogenesis
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Regulation and Function of Adult Neurogenesis

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 9958

Special Issue Editor

Dr. Gadi Turgeman

E-Mail Website
Guest Editor
Department of Molecular Biology, Ariel University, Ariel 40700, Israel
Interests: mesenchymal stem cells; neurogenesis; neurobehavioral disorders; neuroinflammation; brain injury

Special Issue Information

Dear Colleagues,

Behavioral neuroscience has evolved greatly over the past two decades. The growing understanding of the molecular and cellular mechanisms involved in regulating affective and cognitive behavior has opened multiple avenues for future study and intervention. Among the studied mechanisms, adult hippocampal neurogenesis has gained increased attention as it was found to be involved in cognitive behavior, spatial learning, and memory. Furthermore, impaired neurogenesis is involved in neurobehavioral disorders such as Alzheimer’s disease, schizophrenia, depression, and post-traumatic stress disorder, indicating a role of hippocampal neurogenesis in affective behavior as well.  In this Special Issue, we invite papers exploring the mechanisms of neurogenesis, affective and cognitive behavior. Additionally, we welcome functional studies exploring the potential effect of MSC or their products on various behavioral aspects or neurobehavioral disorders. Further studies will increase our understanding of the molecular mechanisms involved in affective and cognitive behavior and may suggest novel therapeutic strategies for adult neurogenesis.

Dr. Gadi Turgeman
Guest Editor

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Published Papers (4 papers)

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Research

25 pages, 4116 KiB  
Article
Parental Preconception and Pre-Hatch Exposure to a Developmental Insult Alters Offspring’s Gene Expression and Epigenetic Regulations: An Avian Model
by Issam Rimawi, Gadi Turgeman, Nataly Avital-Cohen, Israel Rozenboim and Joseph Yanai
Int. J. Mol. Sci. 2023, 24(5), 5047; https://doi.org/10.3390/ijms24055047 - 6 Mar 2023
Cited by 2 | Viewed by 2320
Abstract
Parental exposure to insults was initially considered safe if stopped before conception. In the present investigation, paternal or maternal preconception exposure to the neuroteratogen chlorpyrifos was investigated in a well-controlled avian model (Fayoumi) and compared to pre-hatch exposure focusing on molecular [...] Read more.
Parental exposure to insults was initially considered safe if stopped before conception. In the present investigation, paternal or maternal preconception exposure to the neuroteratogen chlorpyrifos was investigated in a well-controlled avian model (Fayoumi) and compared to pre-hatch exposure focusing on molecular alterations. The investigation included the analysis of several neurogenesis, neurotransmission, epigenetic and microRNA genes. A significant decrease in the vesicular acetylcholine transporter (SLC18A3) expression was detected in the female offspring in the three investigated models: paternal (57.7%, p < 0.05), maternal (36%, p < 0.05) and pre-hatch (35.6%, p < 0.05). Paternal exposure to chlorpyrifos also led to a significant increase in brain-derived neurotrophic factor (BDNF) gene expression mainly in the female offspring (27.6%, p < 0.005), while its targeting microRNA, miR-10a, was similarly decreased in both female (50.5%, p < 0.05) and male (56%, p < 0.05) offspring. Doublecortin’s (DCX) targeting microRNA, miR-29a, was decreased in the offspring after maternal preconception exposure to chlorpyrifos (39.8%, p < 0.05). Finally, pre-hatch exposure to chlorpyrifos led to a significant increase in protein kinase C beta (PKCß; 44.1%, p < 0.05), methyl-CpG-binding domain protein 2 (MBD2; 44%, p < 0.01) and 3 (MBD3; 33%, p < 0.05) genes expression in the offspring. Although extensive studies are required to establish a mechanism–phenotype relationship, it should be noted that the current investigation does not include phenotype assessment in the offspring. Full article
(This article belongs to the Special Issue Regulation and Function of Adult Neurogenesis)
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15 pages, 2803 KiB  
Article
Polarized Anti-Inflammatory Mesenchymal Stem Cells Increase Hippocampal Neurogenesis and Improve Cognitive Function in Aged Mice
by Matanel Tfilin, Nikolai Gobshtis, David Fozailoff, Vadim E. Fraifeld and Gadi Turgeman
Int. J. Mol. Sci. 2023, 24(5), 4490; https://doi.org/10.3390/ijms24054490 - 24 Feb 2023
Cited by 4 | Viewed by 2439
Abstract
Age-related decline in cognitive functions is associated with reduced hippocampal neurogenesis caused by changes in the systemic inflammatory milieu. Mesenchymal stem cells (MSC) are known for their immunomodulatory properties. Accordingly, MSC are a leading candidate for cell therapy and can be applied to [...] Read more.
Age-related decline in cognitive functions is associated with reduced hippocampal neurogenesis caused by changes in the systemic inflammatory milieu. Mesenchymal stem cells (MSC) are known for their immunomodulatory properties. Accordingly, MSC are a leading candidate for cell therapy and can be applied to alleviate inflammatory diseases as well as aging frailty via systemic delivery. Akin to immune cells, MSC can also polarize into pro-inflammatory MSC (MSC1) and anti-inflammatory MSC (MSC2) following activation of Toll-like receptor 4 (TLR4) and TLR3, respectively. In the present study, we apply pituitary adenylate cyclase-activating peptide (PACAP) to polarize bone-marrow-derived MSC towards an MSC2 phenotype. Indeed, we found that polarized anti-inflammatory MSC were able to reduce the plasma levels of aging related chemokines in aged mice (18-months old) and increased hippocampal neurogenesis following systemic administration. Similarly, aged mice treated with polarized MSC displayed improved cognitive function in the Morris water maze and Y-maze assays compared with vehicle- and naïve-MSC-treated mice. Changes in neurogenesis and Y-maze performance were negatively and significantly correlated with sICAM, CCL2 and CCL12 serum levels. We conclude that polarized PACAP-treated MSC present anti-inflammatory properties that can mitigate age-related changes in the systemic inflammatory milieu and, as a result, ameliorate age related cognitive decline. Full article
(This article belongs to the Special Issue Regulation and Function of Adult Neurogenesis)
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19 pages, 4939 KiB  
Article
Effects of Positive Fighting Experience and Its Subsequent Deprivation on the Expression Profile of Mouse Hippocampal Genes Associated with Neurogenesis
by Olga E. Redina, Vladimir N. Babenko, Dmitry A. Smagin, Irina L. Kovalenko, Anna G. Galyamina, Vadim M. Efimov and Natalia N. Kudryavtseva
Int. J. Mol. Sci. 2023, 24(3), 3040; https://doi.org/10.3390/ijms24033040 - 3 Feb 2023
Cited by 1 | Viewed by 2155
Abstract
The hippocampus is known as the brain region implicated in visuospatial processes and processes associated with learning and short- and long-term memory. An important functional characteristic of the hippocampus is lifelong neurogenesis. A decrease or increase in adult hippocampal neurogenesis is associated with [...] Read more.
The hippocampus is known as the brain region implicated in visuospatial processes and processes associated with learning and short- and long-term memory. An important functional characteristic of the hippocampus is lifelong neurogenesis. A decrease or increase in adult hippocampal neurogenesis is associated with a wide range of neurological diseases. We have previously shown that in adult male mice with a chronic positive fighting experience in daily agonistic interactions, there is an increase in the proliferation of progenitor neurons and the production of young neurons in the dentate gyrus (in hippocampus), and these neurogenesis parameters remain modified during 2 weeks of deprivation of further fights. The aim of the present work was to identify hippocampal genes associated with neurogenesis and involved in the formation of behavioral features in mice with the chronic experience of wins in aggressive confrontations, as well as during the subsequent 2-week deprivation of agonistic interactions. Hippocampal gene expression profiles were compared among three groups of adult male mice: chronically winning for 20 days in the agonistic interactions, chronically victorious for 20 days followed by the 2-week deprivation of fights, and intact (control) mice. Neurogenesis-associated genes were identified whose transcription levels changed during the social confrontations and in the subsequent period of deprivation of fights. In the experimental males, some of these genes are associated with behavioral traits, including abnormal aggression-related behavior, an abnormal anxiety-related response, and others. Two genes encoding transcription factors (Nr1d1 and Fmr1) were likely to contribute the most to the between-group differences. It can be concluded that the chronic experience of wins in agonistic interactions alters hippocampal levels of transcription of multiple genes in adult male mice. The transcriptome changes get reversed only partially after the 2-week period of deprivation of fights. The identified differentially expressed genes associated with neurogenesis and involved in the control of a behavior/neurological phenotype can be used in further studies to identify targets for therapeutic correction of the neurological disturbances that develop in winners under the conditions of chronic social confrontations. Full article
(This article belongs to the Special Issue Regulation and Function of Adult Neurogenesis)
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18 pages, 7492 KiB  
Article
FOXG1 Contributes Adult Hippocampal Neurogenesis in Mice
by Jia Wang, Hong-Ru Zhai, Si-Fei Ma, Hou-Zhen Shi, Wei-Jun Zhang, Qi Yun, Wen-Jun Liu, Zi-Zhong Liu and Wei-Ning Zhang
Int. J. Mol. Sci. 2022, 23(23), 14979; https://doi.org/10.3390/ijms232314979 - 29 Nov 2022
Cited by 8 | Viewed by 2248
Abstract
Strategies to enhance hippocampal precursor cells efficiently differentiate into neurons could be crucial for structural repair after neurodegenerative damage. FOXG1 has been shown to play an important role in pattern formation, cell proliferation, and cell specification during embryonic and early postnatal neurogenesis. Thus [...] Read more.
Strategies to enhance hippocampal precursor cells efficiently differentiate into neurons could be crucial for structural repair after neurodegenerative damage. FOXG1 has been shown to play an important role in pattern formation, cell proliferation, and cell specification during embryonic and early postnatal neurogenesis. Thus far, the role of FOXG1 in adult hippocampal neurogenesis is largely unknown. Utilizing CAG-loxp-stop-loxp-Foxg1-IRES-EGFP (Foxg1fl/fl), a specific mouse line combined with CreAAV infusion, we successfully forced FOXG1 overexpressed in the hippocampal dentate gyrus (DG) of the genotype mice. Thereafter, we explored the function of FOXG1 on neuronal lineage progression and hippocampal neurogenesis in adult mice. By inhibiting p21cip1 expression, FOXG1-regulated activities enable the expansion of the precursor cell population. Besides, FOXG1 induced quiescent radial-glia like type I neural progenitor, giving rise to intermediate progenitor cells, neuroblasts in the hippocampal DG. Through increasing the length of G1 phase, FOXG1 promoted lineage-committed cells to exit the cell cycle and differentiate into mature neurons. The present results suggest that FOXG1 likely promotes neuronal lineage progression and thereby contributes to adult hippocampal neurogenesis. Elevating FOXG1 levels either pharmacologically or through other means could present a therapeutic strategy for disease related with neuronal loss. Full article
(This article belongs to the Special Issue Regulation and Function of Adult Neurogenesis)
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