alpha-Tocopherol and ascorbic acid prevent memory deficits provoked by chronic hyperprolinemia in rats.

In the present study we investigated the action of α-tocopherol and ascorbic acid on the effects elicited by chronic hyperprolinemia on rat performance in the Morris water maze. Rats received subcutaneous injections of proline (experimental group) twice a day, with 10 h-interval, from the 6 to 28th days of age or an equivalent volume of 0.9% saline solution (controls). Half of the proline-treated group also received intraperitoneal administration of α-tocopherol (40 mg/kg) and of ascorbic acid (100 mg/kg) from the 6 to 28th days of life. On the 60th day of life, rats were subjected to testing in the water maze. Results show that chronic proline administration provokes impairment on spatial learning in reference memory task, as revealed by the increase of latency in acquisition, in the probe trial and in crossing over the platform location, as well as by the number of crossings, when compared to saline-treated animals. Proline-treated rats also demonstrated a reduced efficiency to find the platform position in the working memory task. Rats chronically treated with proline plus α-tocopherol and ascorbic acid had above effects prevented, suggesting the participation of oxidative stress in such effects. Our findings lend support to a novel therapeutic strategy, based on these vitamins, to the cognitive dysfunction associated with hyperprolinemia type II.