Prevention of Glutamate-Induced Neurotoxicity in Aging Brain by Certain Types of B Vitamins

Glutamate (Glu) acts as an excitatory neurotransmitter in the brain. Excessive levels of Glu in the brain are cytotoxic and lead to severalneurodegenerative processes. Rapid removal of the released Glu in synaptic cliff may prevent the excessive excitation of Glu receptors. The enzymes glutamate decarboxylase (GAD), glutamate transaminases (GOT and GPT) glutamine synthetase (GS) use Glu as substrateand have curtail role in maintaining Glu concentrations below excitatory levels in the brain synaptic cleft. Since Glu-induced neurotoxicity play a key role in Alzheimer’s disease and Parkinson disease’s, this studywas undertaken to investigate the efficacy of vitamins B6, vitamin B12 and folic acid on the activities ofGAD, GOT, GPT and GS in aging rat brain. Materials and Methods: Male Wistar rats (3 and 30 months old)were used. Each group were assigned to 3 treatments subgroups: (group I) B6 vitamin rats; (group II) B12 vita in rats; and (group III) foliate rats. The animals were injected with the vitamins (10mg/Kg/day) for 30 days and the day after the last injection the animalswere killed by decapitated. Forebrains were removed and homogenized in phosphate buffer (pH=7.4). This homogenate was centrifuged and the enzyme activities were measured in the clear supernatant. The enzymes were measured in the supernatant. Results: The enzymeactivities in aged rat brain were considerably lower compared to young animals. Vitamin B6 induced activation of GAD, GOT and GPT in both ages, but, the differences were more pronounced in aged animals. Vitamin B12 and folic acid stimulate the activity of GS in both young and old animals, but had limited effects on GAD, GOT and GPT of both ages. Conclusion: It is concluded that Glu metabolism might be considered as a therapeutic target for prevention of neurodegenerative disorders and age related symptoms.