Transient Impairment of Hippocampus-dependent Learning and Memory in Relatively Low-Dose of Acute Radiation Syndrome is Associated with Inhibition of Hippocampal Neurogenesis

Abstract Background The dentate gyrus exhibits life-long neurogenesis of granule-cell neurons, supporting hippocampal dependent learning and memory. Both temporal lobe epilepsy patients and animal models frequently have hippocampal-dependent learning and memory difficulties and show evidence of reduced neurogenesis. Animal and human temporal lobe epilepsy studies have also shown strong innate immune system activation, which in animal models reduces hippocampal neurogenesis. We sought to determine if and how neuroinflammation signals reduced neurogenesis in the epileptic human hippocampus and its potential reversibility. Methods We isolated endogenous neural stem cells from surgically resected hippocampal tissue in 15 patients with unilateral hippocampal sclerosis. We examined resultant neurogenesis after growing them either as neurospheres in an ideal environment, in 3D cultures which preserved the inflammatory microenvironment and/or in 2D cultures which mimicked it. Results 3D human hippocampal cultures largely replicated the cellular composition and inflammatory environment of the epileptic hippocampus. The microenvironment of sclerotic human epileptic hippocampal tissue is strongly anti-neurogenic, with sustained release of the proinflammatory proteins HMGB1 and IL-1β. IL-1β and HMGB1 significantly reduce human hippocampal neurogenesis and blockade of their IL-1R and TLR 2/4 receptors by IL1Ra and Box-A respectively, significantly restores neurogenesis in 2D and 3D culture. Conclusion Our results demonstrate a HMGB1 and IL-1β-mediated environmental anti-neurogenic effect in human TLE, identifying both the IL-1R and TLR 2/4 receptors as potential drug targets for restoring human hippocampal neurogenesis in temporal lobe epilepsy.

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Learning, Neurogenesis, and Effects of Flavonoids on Learning

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521666210707120719 ◽

2021 ◽

Vol 21 ◽

Author(s):

Asan Yalmaz Hasan Almulla ◽

Rasim Mogulkoc ◽

Abdulkerim Kasim Baltaci ◽

Dervis Dasdelen

Keyword(s):

Learning And Memory ◽

Neural Circuits ◽

Brain Regions ◽

Hippocampal Neurogenesis ◽

Adult Brain ◽

Factors Affecting ◽

Different Types ◽

Mature Neurons ◽

Dependent Learning ◽

The Brain

: Learning and memory are two of our mind's most magical abilities. Different brain regions have roles in processing and storing different types of memories. The hippocampus is the part of the brain responsible for receiving information and storing it in the neocortex. One of the most impressive characteristics of the hippocampus is its capacity for neurogenesis, which is a process in which new neurons are produced and then transformed into mature neurons and finally integrated into neural circuits. The neurogenesis process in the hippocampus, an example of neuroplasticity in the adult brain, is believed to aid hippocampal-dependent learning and memory. New neurons are constantly produced in the hippocampus and integrated into the pre-existing neuronal network; this allows old memories already stored in the neocortex to be removed from the hippocampus and replaced with new ones. Factors affecting neurogenesis in the hippocampus may also affect hippocampal-dependent learning and memory. The flavonoids can particularly exert powerful actions in mammalian cognition and improve hippocampal-dependent learning and memory by positively affecting hippocampal neurogenesis.

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Cyclophosphamide impairs hippocampus-dependent learning and memory in adult mice: Possible involvement of hippocampal neurogenesis in chemotherapy-induced memory deficits

Neurobiology of Learning and Memory ◽

10.1016/j.nlm.2010.01.006 ◽

2010 ◽

Vol 93 (4) ◽

pp. 487-494 ◽

Cited By ~ 86

Author(s):

Miyoung Yang ◽

Joong-Sun Kim ◽

Myoung-Sub Song ◽

Sung-Ho Kim ◽

Seong Soo Kang ◽

...

Keyword(s):

Learning And Memory ◽

Memory Deficits ◽

Hippocampal Neurogenesis ◽

Adult Mice ◽

Dependent Learning

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Cadmium Exposure Impairs Adult Hippocampal Neurogenesis

Toxicological Sciences ◽

10.1093/toxsci/kfz152 ◽

2019 ◽

Vol 171 (2) ◽

pp. 501-514 ◽

Cited By ~ 3

Author(s):

Hao Wang ◽

Glen M Abel ◽

Daniel R Storm ◽

Zhengui Xia

Keyword(s):

Signaling Pathways ◽

Learning And Memory ◽

Hippocampal Neurons ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Mitogen Activated Protein Kinase ◽

Dependent Learning ◽

Cd Exposure

Abstract Cadmium (Cd) is an environmental pollutant of considerable interest throughout the world and potentially a neurotoxicant. Our recent data indicate that Cd exposure induces impairment of hippocampus-dependent learning and memory in mice. However, the underlying mechanisms for this defect are not known. The goal of this study was to determine if Cd inhibits adult neurogenesis and to identify underlying signaling pathways responsible for this impairment. Adult hippocampal neurogenesis is a process in which adult neural progenitor/stem cells (aNPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG) generate functional new neurons in the hippocampus which contributes to hippocampus-dependent learning and memory. However, studies concerning the effects of neurotoxicants on adult hippocampal neurogenesis and the underlying signaling mechanisms are limited. Here, we report that Cd significantly induces apoptosis, inhibits proliferation, and impairs neuronal differentiation in primary cultured aNPCs derived from the SGZ. In addition, the c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase signaling pathways are activated by Cd and contribute to its toxicity. Furthermore, we exposed 8-week-old male C57BL/6 mice to Cd through drinking water for 13 weeks to assess the effects of Cd on adult hippocampal neurogenesis in vivo. Cd treatment reduced the number of 5-week-old adult-born cells in the DG and impaired the differentiation of adult-born hippocampal neurons. These results suggest that Cd exposure impairs adult hippocampal neurogenesis both in vitro and in vivo. This may contribute to Cd-mediated inhibition of hippocampus-dependent learning and memory.

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IL-1β and HMGB1 are anti-neurogenic to endogenous neural stem cells in the sclerotic epileptic human hippocampus

10.21203/rs.3.rs-402363/v1 ◽

2021 ◽

Author(s):

Malik Zaben ◽

Niels Haan ◽

Feras Sharouf ◽

Aminul Ahmed ◽

Lars Sundstrom ◽

...

Keyword(s):

Stem Cells ◽

Animal Models ◽

Neural Stem Cells ◽

Temporal Lobe Epilepsy ◽

Learning And Memory ◽

Temporal Lobe ◽

Hippocampal Neurogenesis ◽

Human Hippocampus ◽

Dependent Learning ◽

Endogenous Neural Stem Cells

Abstract Background: The dentate gyrus exhibits life-long neurogenesis of granule-cell neurons, supporting hippocampal dependent learning and memory. Both temporal lobe epilepsy patients and animal models frequently have hippocampal-dependent learning and memory difficulties and show evidence of reduced neurogenesis. Animal and human temporal lobe epilepsy studies have also shown strong innate immune system activation, which in animal models reduces hippocampal neurogenesis. We sought to determine if and how neuroinflammation signals reduced neurogenesis in the epileptic human hippocampus and its potential reversibility.Methods: We isolated endogenous neural stem cells from surgically resected hippocampal tissue in 15 patients with unilateral hippocampal sclerosis. We examined resultant neurogenesis after growing them either as neurospheres in an ideal environment, in 3D cultures which preserved the inflammatory microenvironment and/or in 2D cultures which mimicked it.Results: 3D human hippocampal cultures largely replicated the cellular composition and inflammatory environment of the epileptic hippocampus. The microenvironment of sclerotic human epileptic hippocampal tissue is strongly anti-neurogenic, with sustained release of the proinflammatory proteins HMGB1 and IL-1β. IL-1β and HMGB1 significantly reduce human hippocampal neurogenesis and blockade of their IL-1R and TLR 2/4 receptors by IL1Ra and Box-A respectively, significantly restores neurogenesis in 2D and 3D culture. Conclusion: Our results demonstrate a HMGB1 and IL-1β-mediated environmental anti- neurogenic effect in human TLE, identifying both the IL-1R and TLR 2/4 receptors as potential drug targets for restoring human hippocampal neurogenesis in temporal lobe epilepsy.

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Low-Dose Sevoflurane Promotes Hippocampal Neurogenesis and Facilitates the Development of Dentate Gyrus-Dependent Learning in Neonatal Rats

ASN NEURO ◽

10.1177/1759091415575845 ◽

2015 ◽

Vol 7 (2) ◽

pp. 175909141557584 ◽

Cited By ~ 10

Author(s):

Chong Chen ◽

Feng-Yan Shen ◽

Xuan Zhao ◽

Tao Zhou ◽

Dao-Jie Xu ◽

...

Keyword(s):

Dentate Gyrus ◽

Low Dose ◽

Hippocampal Neurogenesis ◽

Neonatal Rats ◽

Dependent Learning

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Involvement of Adult Hippocampal Neurogenesis in Learning and Forgetting

Neural Plasticity ◽

10.1155/2015/717958 ◽

2015 ◽

Vol 2015 ◽

pp. 1-13 ◽

Cited By ~ 60

Author(s):

Suk-yu Yau ◽

Ang Li ◽

Kwok-Fai So

Keyword(s):

Learning And Memory ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Pattern Separation ◽

Detailed Mechanism ◽

Continuous Generation ◽

Adult Born Neurons ◽

Newborn Neurons ◽

Dependent Learning ◽

The Relationship

Adult hippocampal neurogenesis is a process involving the continuous generation of newborn neurons in the hippocampus of adult animals. Mounting evidence has suggested that hippocampal neurogenesis contributes to some forms of hippocampus-dependent learning and memory; however, the detailed mechanism concerning how this small number of newborn neurons could affect learning and memory remains unclear. In this review, we discuss the relationship between adult-born neurons and learning and memory, with a highlight on recently discovered potential roles of neurogenesis in pattern separation and forgetting.

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