Effects of vitamin B6 on age associated changes of rat brain glutamate decarboxylase activity

Abstract

Glutamate and gamma-aminobutyric acid (GABA), act as excitatory and inhibitory neurotransmitters in CNS respectively. An increase in glutamate and a decrease in GABA concentration were observed in aged brain. However, the mechanism of these changes has not been very well elucidated. Glutamate decarboxylase (GAD) catalyzes the conversion of glutamate to GABA. Since the vitamin B6 is essential for the activities of GAD, this study was undertaken to investigate the effects of vitamin B6 administration on age related changes in rat brain. The animals were injected intraperitoneally with 1, 10 and 100 mg vitamin B6 /kg body weight /day for 30 days, and specific activity of GAD was assayed in the brain supernatant. The activity of the enzyme in aged rats was significantly lower as compared to that of young animals. Vitamin B6 induced activation of the brain enzyme in both ages, but the rate of the activation was markedly pronounced in aged animals. Significant activation rate of GAD by vitamin B6 in aged rat brain may be resulted from either lower availability of vitamin B6 in aged animals, or lower affinity of the enzyme for pyridoxal -5-phosphate, which is likely to be related to conformational changes of the enzyme during aging. It is suggested that vitamin B6 may restore the activity of the brain glutamate decarboxylase in aged rat.

Monosodium glutamate influences depressive behavior of two age groups of mice in forced swimming test: Vitamin B6 could remedy the situation

“…Therefore plausibly single dose of MSG did not have depressogenic effects in adult mice because of the matured BBB. In addition age associated changes in brain neurotransmitters' metabolism are thought to be important and could possibly lead to many age-related symptoms [20]. Vitamin B6 had beneficial antidepressant effects in both age groups.…”

“…Previously results showed that GAD activity is considerably reduced in the brain of old rats compared to the young animals [20]. That could influence the glutamate and GABA level concentration in favor of glutamate accumulations in certain brain regions [20].…”

“…The GABA inhibitory effects play an important role in the protection of the brain neurons, vitamin B6 derivative pyridoxal 5phosphate (PLP) is a cofactor of GAD [22]. Previously results showed that GAD activity is considerably reduced in the brain of old rats compared to the young animals [20]. That could influence the glutamate and GABA level concentration in favor of glutamate accumulations in certain brain regions [20].…”

“…Vitamin B6, folate, and vitamin B12 are biochemically involved in the metabolism of homocysteine, methionine, and other essential amino acids [18]. These B vitamins through their role as cofactors contribute to numerous catalytic reactions in the human body, which are required for neurotransmitter synthesis and functioning and myelination of the spinal cord and brain [18][19][20][21]. Thus they are involved in optimal functioning of the central nervous system.…”

Effects of Vitamin B6 on the Brain Glutamate Pyrovate Transaminase and Glutamate Oxaloacetate Transaminase in Young and Old Rats

“…Age related decreases in the expression and or activities of these enzymes in the brain have been very well established (9,10). Recently we have reported that the activity of GAD in aged rats brain was 54% lower than that of young animals, which could be reactivated to the levels equivalent to young animals by administration of vitamin B6 [11]. Because pyridoxal 5'-phosphate acts as co-enzyme for aminotransferases as well, this study was extended to examine the effects of vitamin B6 administration on the brain glutamate pyrovate transaminase (GPT) and glutamate oxaloacetate transaminase (GOT)) in young and old rats.…”