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Methamphetamine-induced neuroinflammation and neuronal dysfunction in the mice hippocampus: preventive effect of indomethacin
- Source :
- Repositório Científico de Acesso Aberto de Portugal, Repositório Científico de Acesso Aberto de Portugal (RCAAP), instacron:RCAAP
- Publication Year :
- 2010
- Publisher :
- Wiley, 2010.
-
Abstract
- 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.
- Subjects :
- Male
Indomethacin
Excitotoxicity
Hippocampal formation
medicine.disease_cause
Hippocampus
Methamphetamine
Mice
chemistry.chemical_compound
Neurons
CD11b Antigen
Metabolismo, Medicina básica
Microglia
Glial fibrillary acidic protein
biology
Qa-SNARE Proteins
General Neuroscience
Anti-Inflammatory Agents, Non-Steroidal
Intracellular Signaling Peptides and Proteins
Medicina básica [Ciências médicas e da saúde]
medicine.anatomical_structure
Receptors, Tumor Necrosis Factor, Type I
Tumor necrosis factor alpha
Disks Large Homolog 4 Protein
Neuroglia
medicine.drug
medicine.medical_specialty
Synaptosomal-Associated Protein 25
Synaptophysin
Internal medicine
Basic medicine [Medical and Health sciences]
Glial Fibrillary Acidic Protein
medicine
Animals
Receptors, Tumor Necrosis Factor, Type II
Neuroinflammation
Inflammation
Tumor Necrosis Factor-alpha
Membrane Proteins
Meth
Mice, Inbred C57BL
Endocrinology
nervous system
chemistry
Immunology
biology.protein
Metabolism, Basic medicine
Central Nervous System Stimulants
Guanylate Kinases
Subjects
Details
- ISSN :
- 14609568 and 0953816X
- Volume :
- 31
- Database :
- OpenAIRE
- Journal :
- European Journal of Neuroscience
- Accession number :
- edsair.doi.dedup.....593440dfa5a80c4bf0f3d6d89c8d4584