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Adiponectin protects rat hippocampal neurons against excitotoxicity

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Abstract

Adiponectin exerts multiple regulatory functions in the body and in the hypothalamus primarily through activation of its two receptors, adiponectin receptor1 and adiponectin receptor 2. Recent studies have shown that adiponectin receptors are widely expressed in other areas of the brain including the hippocampus. However, the functions of adiponectin in brain regions other than the hypothalamus are not clear. Here, we report that adiponectin can protect cultured hippocampal neurons against kainic acid-induced (KA) cytotoxicity. Adiponectin reduced the level of reactive oxygen species, attenuated apoptotic cell death, and also suppressed activation of caspase-3 induced by KA. Pretreatment of hippocampal primary neurons with an AMPK inhibitor, compound C, abolished adiponectin-induced neuronal protection. The AMPK activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, attenuated KA-induced caspase-3 activity. These findings suggest that the AMPK pathway is critically involved in adiponectin-induced neuroprotection and may mediate the antioxidative and anti-apoptotic properties of adiponectin.

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Abbreviations

AdipoR1:

Adiponectin receptor 1

AdipoR2:

Adiponectin receptor 2

KA:

Kainic acid

AMPK:

AMP-activated protein kinase

AICAR:

5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside

ROS:

Reactive oxygen species

CR:

Calorie restriction

AD:

Alzheimer’s disease

PD:

Parkinson’s disease

DR:

Dietary restriction

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Acknowledgments

The authors would like to thank Drs. Min Zhu and Haiyang Jiang for technical assistance, Dr. Peter Rapp for suggestions and thoughtful review of the manuscript and Kris Rozankowski for editing the manuscript. This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, USA

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Authors and Affiliations

  1. Department of Neurology, Nanfang Hospital, Nanfang Medical University, Guangzhou, China

    Guang Qiu

  2. Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China

    Guang Qiu, Suk-Yu Yau & Kwok-Fai So

  3. Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD, USA

    Ruiqian Wan, Mark P. Mattson & Marc Gleichmann

  4. Laboratory of Experimental Gerontology, National Institute on Aging, Baltimore, MD, 21224, USA

    Guang Qiu, Jingping Hu, Edward Spangler & Sige Zou

  5. Department of Nursing, Faculty of Medicine, JiNan University, Guangzhou, China

    Shan Liu

  6. Laboratory of Neuropsychology and Laboratory of Cognitive Affective Neuroscience, HKU Alzheimer’s Disease Research Network, University of Hong Kong, Pokfulam, Hong Kong, China

    Tatia M. C. Lee

  7. Nutritional Neuroscience and Aging Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA

    Donald K. Ingram

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  1. Guang Qiu
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  12. Sige Zou
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Corresponding authors

Correspondence to Kwok-Fai So or Sige Zou.

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Qiu, G., Wan, R., Hu, J. et al. Adiponectin protects rat hippocampal neurons against excitotoxicity. AGE 33, 155–165 (2011). https://doi.org/10.1007/s11357-010-9173-5

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  • DOI: https://doi.org/10.1007/s11357-010-9173-5

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