Limbic Seizures Increase Neuronal Production of Messenger RNA for Nerve Growth Factor

Abstract

Nerve growth factor (NGF) produced by telencephalic neurons provides critical trophic support for cholinergic neurons of the basal forebrain. In situ hybridization and nuclease protection analyses demonstrate that limbic seizures dramatically increase the amount of messenger RNA for NGF in the neurons of the hippocampal dentate gyrus within 1 hour of seizure onset and in broadly distributed neocortical and olfactory forebrain neurons some hours later. The increased messenger RNA species is indistinguishable from messenger RNA for transcript B of the beta subunit of NGF from mouse submandibular gland. Thus, the expression of a known growth factor is affected by unusual physiological activity, suggesting one route through which trophic interactions between neurons in adult brain can be modified.

Absence of a Persistently Elevated 37 kDa Fos-Related Antigen and AP-1-Like DNA-Binding Activity in the Brains of Kainic Acid-TreatedfosB Null Mice

“…Similarly, the expression of proteins believed to be involved in neuronal structure and plasticity, such as GAP43, is induced by seizures (Nedivi et al, 1992;Bendotti et al, 1993;Meberg et al, 1993). In addition, a number of neurotrophins and their receptors are induced by seizures and may be subject to AP-1-mediated regulation (Gall and Isackson, 1989;Zafra et al, 1990;Ernfors et al, 1991;Isackson et al, 1991;Bengzon et al, 1993). Thus, many of the molecules, the expression of which may be influenced by AP-1 transcription factor complexes, can potentially contribute to the physical growth of neurons.…”

Depolarizing stimuli regulate nerve growth factor gene expression in cultured hippocampal neurons.

“…Finally, impulse regulation of NGF may be relevant to the pathogenesis of various disease processes. For example, limbic seizures, which lead to a generalized increase in impulse activity and elevated NGF mRNA in hippocampal neurons (15), may perpetuate epileptic activity through synaptic strengthening.…”

“…For example, fimbrial transection increased NGF expression in neonatal hippocampus, suggesting that afferent innervation regulates target elaboration of the trophic factor (14). Limbic seizures, leading to a generalized increase in impulse activity, dramatically elevate NGF mRNA in hippocampal neurons (15). These observations are of particular interest, since hippocampal neurons normally elaborate the factor that interacts with receptors on innervating basal forebrain terminals (16)(17)(18) and since the basal forebrain-hippocampal system has been the primary brain model used to study central actions ofNGF (19,20).…”

Prenatal choline supplementation attenuates neuropathological response to status epilepticus in the adult rat hippocampus

“…The expression of growth factors is thought to be an important mediator of hippocampal neurogenesis (Cameron et al 1998;Anderson et al, 2002; Lee et al, 2002a; 2002b) and some factors are known to change in response to status epilepticus (Gall & Isackson, 1989;Gall et al, 1991;Mudo et al, 1996;Schmidt-Kastner et al, 1996;Katoh-Semba et al, 1999;Shetty et al, 2004). We therefore quantified hippocampal protein levels (via ELISA) and mRNA levels (via RT-PCR) of the following growth factors known to influence neurogenesis: BDNF, IGF-1, FGF-2, NGF, and NT-3.…”