UNILATERAL HIPPOCAMPAL-LESIONS IN NEWBORN AND ADULT RATS - EFFECTS ONSPATIAL MEMORY AND BDNF GENE-EXPRESSION

Subcortical damage at birth often produces more severe deficits than s imilar lesions in an adult. In the present study, effects of unilatera l electrolytic hippocampal ablations made on postnatal day 1 or in 3-m onth-old adult rats, were compared. Exploratory behavior and spatial n avigation in the Morris water maze (MWM) were assessed 8 and 20 weeks after hippocampal damage. Rats with neonatal damage did not respond to novelty in the environment and did not learn to find the hidden platf orm in the MWM. Rats lesioned as adults did learn the water maze task. but slower than controls. We hypothesized that behavioral deficits ob served in rats lesioned at birth, may be due, in part, to neurochemica l dysfunction of the contralateral hippocampus. Specifically, choliner gic and GABAergic neurotransmission were assessed by measuring choline -acetyltransferase (ChAT) and GABAdecarboxylase (GAD) activity. In add ition, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) mRNA levels were assayed in the remaining (contralateral) hipp ocampus. Of these molecules, only BDNF gene expression was significant ly reduced (by 30%) at 8 and 20 weeks after neonatal and adult unilate ral ablation. The similar reduction in BDNF mRNA in both treatment gro ups does not correspond with the lesion's differential effect on memor y function. However, the more severe learning impairment after neonata l lesion may reflect increased dependence on trophins during developme nt. (C) 1998 Elsevier Science B.V. All rights reserved.