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Intrastriatal methylmalonic acid administration induces rotational behavior and convulsions through glutamatergic
C F de Mello1, J Begnini, R E Jiménez-Bernal
1Departamento de Química, Universidade Federal de Santa Maria, Brazil. cfmello@super.ufsm.br
Abstract:
The effect of intrastriatal administration of methylmalonic acid (MMA), a metabolite that accumulates in methylmalonic aciduria, on behavior of adult male Wistar rats was investigated. After cannula placing, rats received unilateral intrastriatal injections of MMA (buffered to pH 7.4 with NaOH) or NaCl. MMA induced rotational behavior toward the contralateral side of injection and clonic convulsions in a dose-dependent manner. Rotational behavior and convulsions were prevented by intrastriatal preadministration of MK-801 and attenuated by preadministration of succinate. This study provides evidence for a participation of NMDA receptors in the MMA-induced behavioral alterations, where succinate dehydrogenase inhibition seems to have a pivotal role.
Insights
Methylmalonic acid (MMA), accumulating in methylmalonic aciduria, causes dose-dependent behavioral changes in rats. NMDA receptor antagonists and succinate administration mitigate these MMA-induced effects, suggesting a role for NMDA receptors and succinate dehydrogenase.
Area of Science:
- Neuroscience
- Metabolic Disorders
- Pharmacology
Background:
- Methylmalonic aciduria is a metabolic disorder characterized by the accumulation of methylmalonic acid (MMA).
- The neurological effects of MMA accumulation are not fully understood.
- Investigating MMA's impact on behavior is crucial for understanding its pathogenesis.
Purpose of the Study:
- To investigate the behavioral effects of intrastriatal methylmalonic acid (MMA) administration in adult male Wistar rats.
- To explore the potential involvement of NMDA receptors and succinate dehydrogenase in MMA-induced behavioral alterations.
Main Methods:
- Unilateral intrastriatal injections of MMA or NaCl were administered to adult male Wistar rats.
- Behavioral changes, including rotational behavior and convulsions, were observed.
- The effects of MK-801 (an NMDA receptor antagonist) and succinate preadministration were evaluated.
Main Results:
- Intrastriatal MMA induced dose-dependent rotational behavior towards the contralateral side and clonic convulsions.
- Preadministration of MK-801 prevented MMA-induced behaviors.
- Succinate preadministration attenuated MMA-induced rotational behavior and convulsions.
Conclusions:
- NMDA receptors play a significant role in the behavioral alterations induced by MMA.
- Succinate dehydrogenase inhibition appears to be pivotal in the neurotoxic effects of MMA.
- These findings provide insights into the neurological mechanisms underlying methylmalonic aciduria.