Our previous work demonstrated that neuroinflammation evoked by triple repeated central LPS challenges inhibited adult hippocampal neurogenesis that were correlated with the depressive-like behavioral symptoms induced by neuroinflammation. These findings suggest that hippocampal neurogenesis might be one of biological mechanisms underlying depression induced by neuroinflammation and targeting neurogenesis might lead to new therapeutic strategies for the treatment of depression. In this study, we manipulated adult hippocampal neurogenesis using fibroblast growth factor 2 (FGF2), one crucial molecule modulating cell proliferation and survival in central nervous system, and investigate the involvement and the potential therapeutic effects of FGF2 on neuroinflammation-induced depression. Central lipopolysaccharides (LPS) challenges were used as previously to evoke the neuroinflammatory state in the brain of rat. Exogenous FGF2 was infused into lateral ventricle during the neuroinflammatory state. It was found that the protein expression of FGF2 in hippocampus was inhibited by neuroinflammation. The activation of extracellular signal-regulated kinase (ERK), the downstream molecule of FGF2, was also inhibited by neuroinflammation. Exogenous FGF2 infusions prevented the decrease in phosphorylation of ERK1/2 under neuroinflammation state. Exogenous FGF2 reversed depressive-like behaviors and the impaired hippocampal neurogenesis induced by neuroinflammation. These findings provide evidence that the FGF2-ERK1/2 pathway is involved in the pathophysiology of depressive-like behaviors, and manipulating the neurogenesis pathway is a viable therapeutic approach to inflammation-associated depression.
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http://dx.doi.org/10.1016/j.bbi.2017.05.013 | DOI Listing |
Biol Psychiatry Glob Open Sci
March 2025
Department of Psychiatry, Division of Systems Neuroscience, Columbia University, New York State Psychiatric Institute, New York, New York.
Background: Impairments in behavioral pattern separation (BPS)-the ability to distinguish between similar contexts or experiences-contribute to memory interference and overgeneralization seen in many neuropsychiatric conditions, including depression, anxiety, posttraumatic stress disorder, dementia, and age-related cognitive decline. Although BPS relies on the dentate gyrus and is sensitive to changes in adult hippocampal neurogenesis, its significance as a pharmacological target has not been tested.
Methods: In this study, we applied a human neural stem cell high-throughput screening cascade to identify compounds that increase human neurogenesis.
Cureus
December 2024
School of Allied Health Sciences, Manav Rachna International Institute of Research and Studies, Faridabad, IND.
Introduction: Sleep deprivation (SD), stemming from a myriad of aetiologies, is a prevalent health condition frequently overlooked. It typically impairs memory consolidation and synaptic plasticity, potentially through neuroinflammatory mechanisms and adenosinergic signalling. It is still unclear whether the adenosine A1 receptor (A1R) modulates SD-induced neurological deficits in the hippocampus.
View Article and Find Full Text PDFBrain Behav Immun
January 2025
Chemotherapy remains the primary treatment modality for multiple cancer types, but the cytotoxicity of chemotherapeutic drugs often leads to persistent psychological disturbances that undermine daily function. Minimizing such unwanted effects is challenging in the rehabilitation/prehabilitation of cancer survivors, hence the impetus to identify modifiable external factors capable of improving the recovery process. The importance of social stimulation has been demonstrated in a mouse model showing that grouped housing lowered the likelihood of developing mood disturbance following exposure to chemotherapeutic drugs compared with isolated housing.
View Article and Find Full Text PDFNeural Regen Res
January 2025
Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Adult hippocampal neurogenesis is linked to memory formation In the adult brain, with new neurons in the hippocampus exhibiting greater plasticity during their immature stages compared to mature neurons. Abnormal adult hippocampal neurogenesis is closely associated with cognitive impairment in central nervous system diseases. Targeting and regulating adult hippocampal neurogenesis have been shown to improve cognitive deficits.
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