Related Experiment Video
Updated: Jun 17, 2026
Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic Poly(I:C)
Published on: March 25, 2016
Methamphetamine-induced neuroinflammation and neuronal dysfunction in the mice hippocampus: preventive effect of
Joana Gonçalves1, Sofia Baptista, Tânia Martins
1Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, Portugal.
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.
Insights
Acute methamphetamine (METH) exposure triggers brain inflammation and neuronal damage. Anti-inflammatory treatment with indomethacin successfully prevented these METH-induced effects in the hippocampus.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Methamphetamine (METH) causes significant neurological and psychiatric damage.
- Mechanisms of acute METH intoxication, particularly neuroinflammation, require further elucidation.
- Recent evidence suggests glial cells play a role in METH-induced neuropathology.
Purpose of the Study:
- To investigate hippocampal dysfunction following acute high-dose METH exposure.
- To analyze the inflammatory response and alterations in neuronal structural proteins.
- To determine if anti-inflammatory treatment can mitigate METH-induced neuroinflammation and neuronal damage.
Main Methods:
- Acute high-dose METH (30 mg/kg) administered intraperitoneally to male C57BL/6J mice.
- Analysis of glial activation (GFAP, CD11b) and TNF system alterations (TNF-alpha, TNFR1).
- Assessment of neuronal protein expression (beta III tubulin, Syntaxin-1, calbindin D28k, tau, synaptophysin) and effect of indomethacin treatment.
Main Results:
- METH induced significant neuroinflammation, characterized by upregulated GFAP, CD11b, TNF-alpha, and TNF receptor 1.
- METH exposure led to altered neuronal protein expression, including downregulated beta III tubulin, Syntaxin-1, calbindin D28k, and tau, with upregulated synaptophysin.
- Indomethacin treatment (10 mg/kg) effectively prevented METH-induced glia activation, TNF system alterations, and beta III tubulin downregulation.
Conclusions:
- Acute high-dose METH triggers a neuroinflammatory cascade in the hippocampus.
- METH intoxication results in significant alterations in neuronal structural proteins, indicating dysfunction.
- Anti-inflammatory intervention with indomethacin can prevent METH-induced neuroinflammation and associated neuronal damage.
