Pharmacological induction of nerve growth factor mRNA in adult rat brain.
Three structurally unrelated compounds, all of which induce nerve growth factor (NGF) in cell culture systems, were assessed for their ability to induce NGF mRNA in adult rat brain using a highly sensitive RNAse protection assay. Interleukin-1 beta (0.5-1 pmol) and 1,25-dihydroxyvitamin D3 (25-25,000 pmol) were extremely potent inducers of NGF mRNA, being respectively at least 50,000 and 4000 times more potent than 4-methylcatechol. These compounds elicited an approximate twofold increase in NGF mRNA in both the hippocampus and cortex, without altering beta-actin mRNA levels after a single intracerebroventricular injection. The duration of NGF induction was dependent on the compound administered. For example, the elevation of NGF mRNA elicited by interleukin-1 beta peaked at 8 h and lasted for at least 24 h. In contrast, the induction of NGF after 1,25-dihydroxyvitamin D3 and 4-methylcatechol administration peaked between 4 and 8 h and was not apparent 24 h after injection. These results demonstrate induction of NGF mRNA in vivo by administration of physiological or pharmacological agents and differentiate these agents by potency and duration of action. Further, these findings indicate that pharmacological induction of NGF may be a viable strategy for the treatment of neurodegenerative disorders such as Alzheimer's disease.
Saporito
M S
MS
Cephalon, Inc., West Chester, Pennsylvania 19380.
Wilcox
H M
HM
Hartpence
K C
KC
Lewis
M E
ME
Vaught
J L
JL
Carswell
S
S
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002396:Catechols; D007375:Interleukin-1; D009414:Nerve Growth Factors; D012333:RNA, Messenger; C018599:4-methylcatechol; D002117:Calcitriol