Exercise-Mediated Neurogenesis in the Hippocampus via BDNF

Liu, Patrick Z.; Nusslock, Robin

doi:10.3389/fnins.2018.00052

Cited by 343 publications

(211 citation statements)

References 75 publications

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“…Wheel running has wide-ranging effects on a variety of molecular and structural changes in the brain that may ameliorate the negative affective states induced by stress, including hippocampal neurogenesis and brain-derived neurotrophic factor (Li et al, 2008;Liu and Nusslock, 2018), so it is possible that the alterations in the galanin system as a result of exercise work in concert with other systems in the brain to lead to an increase in stress resilience. To determine whether increasing galanin in noradrenergic neurons, alone, could recapitulate the anxiolytic effects of exercise, we turned to Gal OX mice.…”

Section: Discussionmentioning

confidence: 99%

Chronic environmental or genetic elevation of galanin in noradrenergic neurons confers stress resilience in mice

Tillage

Wilson

Liles

et al. 2020

Preprint

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Acknowledgements and author contributions:We thank Jason Schroeder for his technical assistance with the behavioral experiments for this study and Cheryl Strauss for helpful editing of the manuscript. RPT and DW conceived, designed, and supervised the project. Behavioral experiments were performed and analyzed by RPT with assistance from GW. In situ hybridization experiments and analysis were performed by RPT with assistance from PVH. Mouse husbandry and genotyping were performed by LCL. RPT and DW wrote the manuscript with input from co-authors.

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Section: Discussionmentioning

confidence: 99%

Chronic environmental or genetic elevation of galanin in noradrenergic neurons confers stress resilience in mice

Tillage

Wilson

Liles

et al. 2020

Preprint

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“…It was also found that a few weeks or several months of physical training causes an increase in the initial BDNF level compared to the state before training, both in healthy subjects and PD patients [150,[160][161][162]. This increase depends on the intensity and duration of the training process [163].…”

Section: Study In Humansmentioning

confidence: 93%

BDNF as a Promising Therapeutic Agent in Parkinson’s Disease

Pałasz

Wysocka

Gąsiorowska

et al. 2020

IJMS

296

197

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Brain-derived neurotrophic factor (BDNF) promotes neuroprotection and neuroregeneration. In animal models of Parkinson's disease (PD), BDNF enhances the survival of dopaminergic neurons, improves dopaminergic neurotransmission and motor performance. Pharmacological therapies of PD are symptom-targeting, and their effectiveness decreases with the progression of the disease; therefore, new therapeutical approaches are needed. Since, in both PD patients and animal PD models, decreased level of BDNF was found in the nigrostriatal pathway, it has been hypothesized that BDNF may serve as a therapeutic agent. Direct delivery of exogenous BDNF into the patient's brain did not relieve the symptoms of disease, nor did attempts to enhance BDNF expression with gene therapy. Physical training was neuroprotective in animal models of PD. This effect is mediated, at least partly, by BDNF. Animal studies revealed that physical activity increases BDNF and tropomyosin receptor kinase B (TrkB) expression, leading to inhibition of neurodegeneration through induction of transcription factors and expression of genes related to neuronal proliferation, survival, and inflammatory response. This review focuses on the evidence that increasing BDNF level due to gene modulation or physical exercise has a neuroprotective effect and could be considered as adjunctive therapy in PD.

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“…Because microglia are myeloid in origin, different from nerve cells, it was believed that microglia influence neuronal behavior through non-contact-dependent pathways 52 . BDNF is an important regulator of hippocampal neurogenesis and is necessary for neurobehavioral plasticity 53,54 . Our results suggest that the pro-neurogenesis effects and therefore the resiliency to stress of IL4-driven Arg1 + microglia depend on BDNF/TrkB signaling.…”

Section: Discussionmentioning

confidence: 99%

IL4-driven microglia modulate stress resilience through BDNF-dependent neurogenesis

Zhang

Rong

Zhang

et al. 2020

Preprint

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Running title: IL4-driven microglia modulate neurogenesis and stress resilience In Brief:Zhang et al. show that IL4-induced Arg1 + microglia restore hippocampal neurogenesis and promote resilience against stress in mice by increasing BDNF levels. Targeting microglia with immunomodulatory factors may be a strategy for treating mood disorders.2 Highlights:1. Vulnerability to stress in mice is associated with reduced IL4 signaling in the hippocampus 2. Brain-derived IL4 promotes adult hippocampal neurogenesis and stress resistance by driving Arg1 + microglia 3. IL4-driven Arg1 + microglia enhance hippocampal neurogenesis via a BDNF-dependent pathway 3 Abstract Adult neurogenesis in the dentate gyrus of the hippocampus is regulated by specific groups of microglia and is functionally implicated in behavioral responses to stress. However, the role of microglia in modulating hippocampal neurogenesis in stress responses remains poorly understood. Here we investigated the effects of IL4-driven Arg1 + microglia in the restoration of hippocampal neurogenesis and conferment of stress resilience. We found that low IL4 levels in the hippocampus of mice was associated with greater stress vulnerability and, conversely, overexpression of IL4 in the hippocampus induced a large number of Arg1 + microglia and ameliorated stress-induced depressive-like behaviors. Knockdown of microglial IL4 receptors in the hippocampus of mice exacerbated the stress-induced inflammatory response and abolished the antidepressant effects of IL4 overexpression. Enhancement or inhibition of IL4 signaling in hippocampal microglia modulated neurogenesis, and blockade of neurogenesis abolished the resilience to stress-induced depression. We further show that IL4-activated microglia is associated with upregulation of BDNF levels and neurogenesis. Taken together, our findings suggest that IL4-driven microglia in the hippocampus trigger BDNF-dependent neurogenesis in response to chronic stress, helping protect against depressive-like symptoms. These findings identify the modulation of a specific microglial phenotype as a treatment strategy for mood disorders.

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Exercise-Mediated Neurogenesis in the Hippocampus via BDNF

Cited by 343 publications

References 75 publications

Chronic environmental or genetic elevation of galanin in noradrenergic neurons confers stress resilience in mice

Chronic environmental or genetic elevation of galanin in noradrenergic neurons confers stress resilience in mice

BDNF as a Promising Therapeutic Agent in Parkinson’s Disease

IL4-driven microglia modulate stress resilience through BDNF-dependent neurogenesis

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