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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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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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