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Expression of heat shock protein (HSP 72 kDa) during acute methamphetamine intoxication depends on brain hyperthermia: neurotoxicity or neuroprotection?

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Abstract

In the present study, light and electron microscopy were used to examine heat shock protein (HSP 72kD) expression during acute methamphetamine (METH) intoxication in rats and evaluate its relationships with brain temperature and alterations in a number of other histochemical and morphological parameters. Freely moving rats received METH at the same dose (9 mg/kg, sc) but at different ambient temperatures (23 and 29°C), showing a wide range of brain temperature elevations (37.6–42.5°C); brains were taken for histochemical and morphological evaluations at peak of brain temperature increase. We found that acute METH intoxication induces massive and wide-spread HSP expression in neural and glial cells examined in detail in the cortex, hippocampus, thalamus, and hypothalamus. In each of these structures, the number of HSP-positive cells tightly correlated with brain temperature elevation. The changes in HSP immunoreactivity were also tightly related to alterations in permeability of the blood–brain barrier, acute glial activation, and brain edema assessed by albumin and GFAP immunoreactivity and measuring tissue water content, respectively. While robust and generalized HSP production normally appears to be the part of an adaptive brain response associated with METH-induced metabolic activation, activation of this protective mechanism has its natural limits and could not counteract the damaging effects of oxidative stress, high temperature, and edema—the leading factors of METH-induced neurotoxicity.

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Acknowledgments

This study was supported by the Intramural Research Program of NIDA-NIH, the Laerdal Foundation of Acute Medicine, Norway, and NIDA Distinguished International Scientist Collaboration Award (NIH) awarded to Hari S. Sharma. The authors greatly appreciate technical assistance of P. Leon Brown (NIDA-IRP) as well as Mari-Anne Carlsson and Inga Hörte (Uppsala University). We wish to thank Drs. Barry Hoffer and Roy A. Wise for support of this study.

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Authors and Affiliations

  1. Behavioral Neuroscience Branch, National Institute on Drug Abuse-Intramural Research Program, NIH, 333 Cassell Drive, Baltimore, MD, 21224, USA

    Eugene A. Kiyatkin

  2. Laboratory of Cerebrovascular Research, Department of Surgical Sciences, University Hospital, Uppsala University, Uppsala, Sweden

    Hari S. Sharma

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  1. Eugene A. Kiyatkin
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  2. Hari S. Sharma
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Correspondence to Eugene A. Kiyatkin.

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Kiyatkin, E.A., Sharma, H.S. Expression of heat shock protein (HSP 72 kDa) during acute methamphetamine intoxication depends on brain hyperthermia: neurotoxicity or neuroprotection?. J Neural Transm 118, 47–60 (2011). https://doi.org/10.1007/s00702-010-0477-5

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  • DOI: https://doi.org/10.1007/s00702-010-0477-5

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