Nerve growth factor increases stimulus-evoked metabolic activity in acetylcholine-depleted barrel cortex.
Lesions of the basal forebrain deplete the neocortex of cholinergic fibers. Acetylcholine depletion in the somatosensory cortex of rats results in reduced stimulus-evoked activity in response to whisker stimulation. Previous studies demonstrate that embryonic basal forebrain transplants improve functional activity toward normal. It is not clear if the activity increase is due to cholinergic replacement or other factors present in the graft. In this study, we examined the possibility that nerve growth factor (NGF), a neurotrophin known as a survival factor and a specific protectant for cholinergic basal forebrain neurons, can preserve basal forebrain cells after a lesion and restore functional activity in the somatosensory cortex. We report that NGF alone is capable of restoring functional activity in the barrel cortex of animals with basal forebrain lesions, while vehicle injections of saline do not alter activity. Both high (10 microg) and low (5 microg) doses of NGF unilaterally injected into the lateral ventricle improved stimulus-evoked functional activity during bilateral whisker stimulation. The mechanism of NGF action is not clear since the restoration of functional activity in cortex was not accompanied by increased cholinergic activity as detected by acetylcholinesterase fiber staining. NGF may act directly on cortical neurons, although its site of action is not well defined.
Rahimi
O
O
Department of Anatomy & Cell Biology, USUHS, Bethesda, MD 20814, USA.
Eslin
D E
DE
Hill
G F
GF
Juliano
S L
SL
D000109:Acetylcholine / Q000172:deficiency*; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D005260:Female; D007091:Image Processing, Computer-Assisted; D007276:Injections, Intraventricular; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D016548:Prosencephalon / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D000963:Antimetabolites; D009414:Nerve Growth Factors; D003847:Deoxyglucose; D000109:Acetylcholine