GABA(B) receptor antagonists elevate both mRNA and protein levels of the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) but not neurotrophin-3 (NT-3) in brain and spinal cord of rats
K. Heese et al., GABA(B) receptor antagonists elevate both mRNA and protein levels of the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) but not neurotrophin-3 (NT-3) in brain and spinal cord of rats, NEUROPHARM, 39(3), 2000, pp. 449-462
In this study we show that single, physiologically-active and non-convulsiv
e doses of the three GABA, receptor antagonists CGP 36742, CGP 56433A and C
GP 56999A increase NGF and BDNF mRNA levels by 200-400% and protein levels
by 200-250% in rat neocortex, hippocampus as well as spinal cord. In all ar
eas examined the increase in NGF protein preceded that of BDNF. Peak levels
of both neurotrophins are transient and occur between 24 and 72 h, dependi
ng on the region. In contrast, NT-3 protein concentrations in the neocortex
and hippocampus were decreased significantly to 50% of control values with
in 48-96 h. The decrease in the spinal cord was less than 30% and did not r
each significant levels. These data clearly demonstrate that GABA(B) recept
or antagonists induce a specific neurotrophin expression in the central ner
vous system at physiologically relevant doses, as opposed to the extreme co
nditions of seizure paradigms.
The results are in line with the concept that neuronal neurotrophin synthes
is and release in brain are controlled by afferent nerve activity.
GABA(B) receptor antagonists could therefore be a valuable new approach to
selectively increase endogenous neurotrophin levels in the central nervous
system. (C) 2000 Elsevier Science Ltd. All rights reserved.