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Disruption of neurogenesis by hypothalamic inflammation in obesity or aging

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Abstract

Adult neural stem cells contribute to neurogenesis and plasticity of the brain which is essential for central regulation of systemic homeostasis. Damage to these homeostatic components, depending on locations in the brain, poses threat to impaired neurogenesis, neurodegeneration, cognitive loss and energy imbalance. Recent research has identified brain metabolic inflammation via proinflammatory IκB kinase-β (IKKβ) and its downstream nuclear transcription factor NF-κB pathway as a non-classical linker of metabolic and neurodegenerative disorders. Chronic activation of the pathway results in impairment of energy balance and nutrient metabolism, impediment of neurogenesis, neural stem cell proliferation and differentiation, collectively converging on metabolic and cognitive decline. Hypothalamic IKKβ/NF-κB via inflammatory crosstalk between microglia and neurons has been discovered to direct systemic aging by inhibiting the production of gonadotropin-releasing hormone (GnRH) and inhibition of inflammation or GnRH therapy could revert aging related degenerative symptoms at least in part. This article reviews the crucial role of hypothalamic inflammation in affecting neural stem cells which mediates the neurodegenerative mechanisms of causing metabolic derangements as well as aging-associated disorders or diseases.

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Acknowledgments

The authors sincerely thank Cai lab members for related research. D.C. is supported by NIH R01 DK078750, R01 AG031774, R01 HL113180, and American Diabetes Association grant 1-12-BS-20. D.C. is a recipient of Irma T. Hirschl Scholarship.

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  1. Department of Molecular Pharmacology, Diabetes Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA

    Sudarshana Purkayastha & Dongsheng Cai

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  1. Sudarshana Purkayastha
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  2. Dongsheng Cai
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Correspondence to Dongsheng Cai.

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Purkayastha, S., Cai, D. Disruption of neurogenesis by hypothalamic inflammation in obesity or aging. Rev Endocr Metab Disord 14, 351–356 (2013). https://doi.org/10.1007/s11154-013-9279-z

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