Methamphetamine-induced neuroinflammation and neuronal dysfunction in the mice hippocampus: preventive effect of indomethacin

• Type: Article in International Scientific Journal
• Date: 2010

Authors

goncalves, joana (Author) Other; baptista, sofia (Author) Other; martins, tania (Author) Other; milhazes, nuno (Author) Other; borges, fernanda (Author) FCUP; ribeiro, carlos f. (Author) Other; malva, joao o. (Author) Other; silva, ana p. (Author) Other

Journal

Title: European Journal of Neuroscience

Vol. 31

Pages: 315-326

ISSN: 0953-816X

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 115 Citations

Scopus - 121 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

CORDIS: Physical sciences > Chemistry > Biochemistry > Metabolism

Other information

Authenticus ID: P-003-ATH

DOI: 10.1111/j.1460-9568.2009.07059.x

Abstract (EN): Methamphetamine (METH) causes irreversible damage to brain cells leading to neurological and psychiatric abnormalities. However, the mechanisms underlying life-threatening effects of acute METH intoxication remain unclear. Indeed, most of the hypotheses focused on intra-neuronal events, such as dopamine oxidation, oxidative stress and excitotoxicity. Yet, recent reports suggested that glia may contribute to METH-induced neuropathology. In the present study, we investigated the hippocampal dysfunction induced by an acute high dose of METH (30 mg/kg; intraperitoneal injection), focusing on the inflammatory process and changes in several neuronal structural proteins. For that, 3-month-old male wild-type C57BL/6J mice were killed at different time-points post-METH. We observed that METH caused an inflammatory response characterized by astrocytic and microglia reactivity, and tumor necrosis factor (TNF) system alterations. Indeed, glial fibrillary acidic protein (GFAP) and CD11b immunoreactivity were upregulated, likewise TNF-alpha and TNF receptor 1 protein levels. Furthermore, the effect of METH on hippocampal neurons was also investigated, and we observed a downregulation in beta III tubulin expression. To clarify the possible neuronal dysfunction induced by METH, several neuronal proteins were analysed. Syntaxin-1, calbindin D28k and tau protein levels were downregulated, whereas synaptophysin was upregulated. We also evaluated whether an anti-inflammatory drug could prevent or diminish METH-induced neuroinflammation, and we concluded that indomethacin (10 mg/kg; i.p.) prevented METH-induced glia activation and both TNF system and beta III tubulin alterations. In conclusion, we demonstrated that METH triggers an inflammatory process and leads to neuronal dysfunction in the hippocampus, which can be prevented by an anti-inflammatory treatment.

Language: English

Type (Professor's evaluation): Scientific