Seizure-Induced Increases in NGF mRNA Exhibit Different Time Courses across Forebrain Regions and Are Biphasic in Hippocampus

Abstract

In the present study, in situ hybridization and S1 nuclease protection analyses were used to evaluate the temporal and spatial parameters of changes in nerve growth factor (NGF) mRNA expression in rat forebrain following hilus lesion-induced recurrent limbic seizures. Seizure-induced increases in NGF mRNA levels were widespread with differences in the temporal parameters of change between brain areas. There were two distinct increases in NGF cRNA hybridization in dentate gyrus stratum granulosum. Hybridization was increased several-fold by 6 h after a seizure-producing hilus lesion (HL), declined to below control values by 12 h post-HL, and then increased again by 24 h post-HL, or 12 h after the termination of seizures. This biphasic increase was corroborated by S1 nuclease protection analysis. In entorhinal cortex, cingulate cortex and neocortex NGF cRNA hybridization was markedly increased first in layers H/III by 6-12 h post-HL and progressed to layers V/VI by 24 h post-HL. Striking increases in NGF mRNA were detected in the majority of amygdaloid nuclei beginning with the cortical nuclei by 12 h postlesion and extending into the more deeply placed nuclei by 24 h postlesion. Labeling was increased in sparsely distributed neurons in the caudate putamen, ventral pallidum, and tenia tecta at 24 h post-HL. In all areas, hybridization declined to control values by 48-96 h post-HL. NGF expression was not changed in some forebrain regions which normally contain NGF mRNA including the diagonal bands of Broca and select thalamic nuclei. These data demonstrate that seizures stimulate NGF expression in many different types of neurons. Moreover, regional differences in the time courses of induction suggest that distinct regulatory mechanisms subserve activity-dependent changes in NGF mRNA expression in different neuronal populations.