The drug cerebrolysin and its peptide fraction E021 increase the abundance of the blood-brain barrier GLUT1 glucose transporter in brains of young and old rats.

Abstract

The brain-derived peptidergic drug Cerebrolysin has been found to support the survival of neurons in vitro and in vivo. In the present study, we investigated the effects of Cerebrolysin and its peptide preparation E021 on spatial learning and memory, as well as on the abundance of the blood-brain barrier GLUT1 glucose transporter (GLUT1) in 2-month-old and 24-month-old rats. Young rats were treated with the drugs or saline (2.5 ml/kg/day) daily on postnatal days 1-7, and old rats for 19 consecutive days. For behavioural testing the Morris water maze was used. The abundance of GLUT1 was determined in brain slices by immunocytochemistry. Quantification of the density of the GLUT1 immunostaining was performed using light microscopy and a computerised image analysing system. All drug-treated rats, young and old, exhibit shorter escape latencies in the water maze, on all testing days (p < 0.01), indicating improved cognitive performance. Immunohistochemical data show an age-related decrease of the density of GLUTI (p < 0.05). In young animals, the administration of the drugs led to an increase of the abundance of GLUT1 in all experimental groups (p < 0.01). In old rats, the treatment with Cerebrolysin, but not with E021, resulted in an increase in the immunoreactive GLUT1 (p < 0.01). The elevated abundance of GLUT1 after the administration of both peptidergic substances might be supportive for the cognitive effects of this drug, by causing an improved nutritional supply of glucose to the neurons.