Experience-dependent regulation of adult hippocampal neurogenesis: Effects of long-term stimulation and stimulus withdrawal

: Traumatic brain injury (TBI) is a serious cause of disability and death among young and adult individuals, displaying complex pathophysiology including cellular and molecular mechanisms that are not fully elucidated. Many experimental and clinical studies investigated the potential relationship between TBI and the process by which neurons are formed in the brain, known as neurogenesis. Currently, there are no available treatments for TBI’s long-term consequences being the search for novel therapeutic targets, a goal of highest scientific and clinical priority. Some studies evaluated the benefits of treatments aimed at improving neurogenesis in TBI. In this scenario, herein, we reviewed current pre-clinical studies that evaluated different approaches to improving neurogenesis after TBI while achieving better cognitive outcomes, which may consist in interesting approaches for future treatments.

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Estrogenic Regulation of Hippocampal Neurogenesis Throughout the Lifespan

Estrogens and Memory ◽

10.1093/oso/9780190645908.003.0016 ◽

2020 ◽

pp. 253-281

Author(s):

Shunya Yagi ◽

Rand S. Eid ◽

Wansu Qiu ◽

Paula Duarte-Guterman ◽

Liisa A. M. Galea

Keyword(s):

Steroid Hormones ◽

Cognitive Training ◽

Adult Female ◽

Ovarian Hormones ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Maternal Experience ◽

Number Of Factors ◽

Estrogenic Regulation

Neurogenesis in the hippocampus exists across a number of species, including humans. Steroid hormones, such as estrogens, modulate neurogenesis dependent on age, reproductive experience and sex. Findings are discussed in the chapter with reference to how neurogenesis in the hippocampus is related to learning and memory. Natural fluctuations in ovarian hormones or removal of ovaries modulate neurogenesis in the short term but not in the long term. Maternal experience has long-lasting effects on neurogenesis in the hippocampus. Acute estrogens increase proliferation in adult female rodents, but influence survival of new neurons dependent on a number of factors including sex, cognitive training, type of estrogen, and whether or not cells were produced under estrogens. This chapter outlines findings indicating that estrogens can be strong modulators of adult hippocampal neurogenesis, which may have implications for disorders involving hippocampal dysfunction that target women.

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Acute and Fractionated Exposure to High-LET56Fe HZE-Particle Radiation Both Result in Similar Long-Term Deficits in Adult Hippocampal Neurogenesis

Radiation Research ◽

10.1667/rr13480.1 ◽

2013 ◽

Vol 180 (6) ◽

pp. 658-667 ◽

Cited By ~ 37

Author(s):

Phillip D. Rivera ◽

Hung-Ying Shih ◽

Junie A. LeBlanc ◽

Mara G. Cole ◽

Wellington Z. Amaral ◽

...

Keyword(s):

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Particle Radiation

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Correction: Long-Term Mild, rather than Intense, Exercise Enhances Adult Hippocampal Neurogenesis and Greatly Changes the Transcriptomic Profile of the Hippocampus

PLoS ONE ◽

10.1371/journal.pone.0133089 ◽

2015 ◽

Vol 10 (7) ◽

pp. e0133089 ◽

Cited By ~ 3

Author(s):

Koshiro Inoue ◽

Masahiro Okamoto ◽

Junko Shibato ◽

Min Chul Lee ◽

Takashi Matsui ◽

...

Keyword(s):

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Intense Exercise ◽

Transcriptomic Profile

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Short- and long-term treatment with modafinil differentially affects adult hippocampal neurogenesis

Neuroscience ◽

10.1016/j.neuroscience.2014.08.014 ◽

2014 ◽

Vol 278 ◽

pp. 267-275 ◽

Cited By ~ 8

Author(s):

M.D. Brandt ◽

E. Ellwardt ◽

A. Storch

Keyword(s):

Term Treatment ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Long Term Treatment ◽

Short And Long Term

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Early-life midazolam exposure persistently changes chromatin accessibility to impair adult hippocampal neurogenesis and cognition

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2107596118 ◽

2021 ◽

Vol 118 (38) ◽

pp. e2107596118

Author(s):

Hiroyoshi Doi ◽

Taito Matsuda ◽

Atsuhiko Sakai ◽

Shuzo Matsubara ◽

Sumio Hoka ◽

...

Keyword(s):

Early Life ◽

Therapeutic Strategy ◽

Pediatric Anesthesia ◽

Chromatin Accessibility ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Voluntary Exercise ◽

Early Life Exposure ◽

Mouse Hippocampus

Linkage between early-life exposure to anesthesia and subsequent learning disabilities is of great concern to children and their families. Here we show that early-life exposure to midazolam (MDZ), a widely used drug in pediatric anesthesia, persistently alters chromatin accessibility and the expression of quiescence-associated genes in neural stem cells (NSCs) in the mouse hippocampus. The alterations led to a sustained restriction of NSC proliferation toward adulthood, resulting in a reduction of neurogenesis that was associated with the impairment of hippocampal-dependent memory functions. Moreover, we found that voluntary exercise restored hippocampal neurogenesis, normalized the MDZ-perturbed transcriptome, and ameliorated cognitive ability in MDZ-exposed mice. Our findings thus explain how pediatric anesthesia provokes long-term adverse effects on brain function and provide a possible therapeutic strategy for countering them.

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Long-Term Mild, rather than Intense, Exercise Enhances Adult Hippocampal Neurogenesis and Greatly Changes the Transcriptomic Profile of the Hippocampus

PLoS ONE ◽

10.1371/journal.pone.0128720 ◽

2015 ◽

Vol 10 (6) ◽

pp. e0128720 ◽

Cited By ~ 68

Author(s):

Koshiro Inoue ◽

Masahiro Okamoto ◽

Junko Shibato ◽

Min Chul Lee ◽

Takashi Matsui ◽

...

Keyword(s):

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Intense Exercise ◽

Transcriptomic Profile

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Long-term exposure to a hypomagnetic field attenuates adult hippocampal neurogenesis and cognition

Nature Communications ◽

10.1038/s41467-021-21468-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Bingfang Zhang ◽

Lei Wang ◽

Aisheng Zhan ◽

Min Wang ◽

Lanxiang Tian ◽

...

Keyword(s):

Cognitive Processes ◽

Geomagnetic Field ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Oxygen Species ◽

Strongly Correlated ◽

Human Beings ◽

Hypomagnetic Field ◽

Dependent Learning

AbstractAdult hippocampal neurogenesis contributes to learning and memory, and is sensitive to a variety of environmental stimuli. Exposure to a hypomagnetic field (HMF) influences the cognitive processes of various animals, from insects to human beings. However, whether HMF exposure affect adult hippocampal neurogenesis and hippocampus-dependent cognitions is still an enigma. Here, we showed that male C57BL/6 J mice exposed to HMF by means of near elimination of the geomagnetic field (GMF) exhibit significant impairments of adult hippocampal neurogenesis and hippocampus-dependent learning, which is strongly correlated with a reduction in the content of reactive oxygen species (ROS). However, these deficits seen in HMF-exposed mice could be rescued either by elevating ROS levels through pharmacological inhibition of ROS removal or by returning them back to GMF. Therefore, our results suggest that GMF plays an important role in adult hippocampal neurogenesis through maintaining appropriate endogenous ROS levels.

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Spatial Training Attenuates Long-Term Alzheimer’s Disease-Related Pathogenic Processes in APP/PS1 Mice

Journal of Alzheimer s Disease ◽

10.3233/jad-215016 ◽

2021 ◽

pp. 1-14

Author(s):

Yang Zhao ◽

Jian Bao ◽

Wei Liu ◽

Xiaokang Gong ◽

Zheng Liang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Β ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Plaque Burden ◽

Amyloid Β Protein ◽

Long Term Effects ◽

Spatial Training

Background: Alzheimer’s disease (AD), with cognitive impairment as the main clinical manifestation, is a progressive neurodegenerative disease. The assembly of amyloid-β (Aβ) as senile plaques is one of the most well-known histopathological alterations in AD. Several studies reported that cognitive training reduced Aβ deposition and delayed memory loss. However, the long-term benefits of spatial training and the underlying neurobiological mechanisms have not yet been elucidated. Objective: To explore the long-term effects of spatial training on AD-related pathogenic processes in APP/PS1 mice. Methods: We used Morris water maze (MWM), Open Field, Barnes Maze, western blotting, qPCR, and immunofluorescence. Results: One-month MWM training in APP/PS1 mice at 2.5 months of age could attenuate Aβ deposition and decrease the expression of β-secretase (BACE1) and amyloid-β protein precursor (AβPP) with long-term effects. Simultaneously, regular spatial training increased the expression of synapse-related proteins in the hippocampus. Moreover, MWM training increased adult hippocampal neurogenesis in AD model mice. Nonetheless, cognitive deficits in APP/PS1 transgenic mice at 7 months of age were not attenuated by MWM training at an early stage. Conclusion: Our study demonstrates that MWM training alleviates amyloid plaque burden and adult hippocampal neurogenesis deficits with long-term effects in AD model mice.

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