Neurotrophic factors alter gene expression in mouse hippocampal neurons

Abstract

The possible age-related involvement of two different signal transduction pathways in the rat CNS was investigated. In the phosphytidyl inostiol (PI) response, higher phospholipase-C (PL-C) activity and drastically higher (almost 2.5-fold) inositol (1,4,5)trisphosphate (Ins(1,4,5) P3) concentration in the corpus striatum (caudate-putamen) of extremely old (approximately 40 months) female Wistar rats in comparison to young adult (approximately 3.5 months) rats were observed. In the adenosine 3′:5′-cyclic monophosphate (cAMP) cascade, a significantly higher endogenus cAMP level and a significant decline of the adenylate cyclase (AC, ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1.) activity were observed in striatal tissue from young rats in comparison with aged rats. Binding saturation experiments with [3H]SCH 23390 at the dopamine (DA) D1 receptor (D1) and [3H]spiperone at the DA D2 receptor (D2) revealed no change in the affinity (Kd) but a significant decrease in the density (Bmax) of D1 (−31%, p<0.005) and of D2 (−22%, p<0.05), respectively, in the aged versus young striata. DA seems to slightly inhibit total inositol phosphate formation and this effect was antagonized by (−)-sulpiride. A significant decrease (p<0.05) in the AC activity stimulated by 10 μM DA in the senescent compared to the young animals was monitored. Apparently, the age-related decline of the AC activity was independent of changes of GS and Gi activity.