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Aspartate-induced neuronal necrosis in infant mice: protective effect of carbohydrate and insulin
M W Finkelstein1, T T Daabees, L D Stegink
1Department of Oral Pathology, University of Iowa, Iowa City 52242.
Insights
Carbohydrate and insulin protect infant mice from aspartate-induced brain damage. These findings suggest potential therapeutic strategies for excitotoxicity in developing brains.
Area of Science:
- Neuroscience
- Toxicology
- Developmental Biology
Background:
- Excitatory amino acids like glutamate and aspartate can cause hypothalamic neuronal necrosis in infant mice.
- Previous research indicates carbohydrate and insulin mitigate glutamate-induced neurotoxicity.
Purpose of the Study:
- To determine if carbohydrate and insulin offer similar neuroprotection against aspartate-induced neuronal damage in infant mice.
- To investigate the efficacy of carbohydrate and insulin in preventing aspartate neurotoxicity.
Main Methods:
- Eight-day-old mice were administered varying doses of aspartate (750 and 1000 mg/kg).
- Mice received simultaneous carbohydrate (1 g/kg) or prior insulin injections alongside aspartate.
- Neuronal necrosis was quantified in hypothalamic sections.
Main Results:
- Aspartate administration led to dose-dependent neuronal necrosis.
- Simultaneous carbohydrate administration significantly reduced aspartate-induced lesions, especially at lower doses.
- Insulin pre-treatment also decreased aspartate neurotoxicity, with greater protection at lower aspartate doses.
- Carbohydrate and insulin had minimal impact on plasma aspartate levels.
Conclusions:
- Carbohydrate and insulin demonstrate a protective effect against aspartate-induced hypothalamic neuronal necrosis in infant mice.
- These findings suggest a potential role for metabolic interventions in managing excitotoxicity during early development.
- The protective mechanisms may not be solely dependent on altering plasma aspartate concentrations.
Abstract:
Infant mice given large doses of glutamate or aspartate develop hypothalamic neuronal necrosis. Studies by others demonstrated that simultaneous administration of carbohydrate or prior injection with insulin markedly decreased glutamate-induced neuronal damage. We investigated whether carbohydrate and insulin exert a similar protective effect against aspartate-induced neuronal necrosis. Eight-day-old mice administered aspartate at 750 and 1000 mg/kg body weight developed neuronal necrosis (45.9 +/- 7.2 and 80.8 +/- 17.3 necrotic neurons/section, respectively). When carbohydrate (1 g/kg body weight) was administered simultaneously no lesions were detected in mice administered 750 mg/kg body weight aspartate, while 30.1 +/- 14.2 necrotic neurons/section were noted at 1000 mg aspartate/kg body weight. Mice administered 1000 mg/kg body weight aspartate with prior injection of insulin had 28.4 +/- 12.6 necrotic neurons/section, while 4.2 +/- 1.4 necrotic neurons/section were noted in insulin treated mice given 750 mg aspartate/kg body weight. Carbohydrate and insulin treatments has only minimal effects on plasma aspartate concentrations.