Effects of L-carnitine on aging-related learning changes and glutamate-mediated molecular mechanisms

Age-related cognitive loss has been linked to a possible imbalance in the brain's oxidant/antioxidant system. Additionally, neurotransmitter concentrations, the activity and levels of receptors change in different brain regions depending on aging. The aim of this study was to investigate the effect of chronic L-carnitine administration on learning and memory in naturally aging rat, focusing on its impact on glutamate cycle and receptors. Sixty male 10-month old male Wistar rats were randomly divided into two groups as control and L-carnitine groups. For a period of 7 months, L-carnitine was given at 50 mg/kg/day via oral gavage. The cognitive performance was assessed by novel object recognition and active avoidance tests. Total oxidant capacity and antioxidant capacity levels as well as glutamate and glutamine concentrations were analyzed in the hippocampi. NMDA and AMPA receptors, VGLUT-1, VGLUT-2, EAAT-1, EAAT-2, EAAT-3 levels in hippocampi were evaluated. L-carnitine administration increased learning performance. Total oxidant capacity levels decreased and total antioxidant capacity levels increased in the hippocampus of aged rats treated with L-carnitine. Furthermore, a small shift in the glutamate and glutamine concentrations between control and L-carnitine treated groups were observed. During the aging process, L-carnitine administration caused an increase in VGLUT-1, VGLUT-2, EAAT-1, EAAT-2, EAAT-3 levels in hippocampus tissues. In addition, NMDAR1 and slightly NMDAR2 mRNA levels increased, while AMPAR1 level decreased in the L-carnitine-treated group. Our data suggest that the molecular and functional changes controlling glutamate homeostasis in the hippocampus with aging may be attenuated by long-term L-carnitine usage.