Cortical second messengers after NBM damage: no change in responses to cholinergic agonists.
Damage to the nucleus basalis of Meynert (NBM) decreases acetylcholine (ACh) innervation of cortex. We explored transmission of cholinergic messages in cortex 2-3 weeks after such damage. The NBM damage was unilateral and the ipsilateral denervated cortex was compared to the contralateral nondenervated cortex. The response to carbachol, a muscarinic ACh receptor-agonist, was measured by inhibition of forskolin-induced cAMP accumulation in cortical membranes and by formation of inositol phosphate (IP) in cortical slices. No difference was found in the carbachol effects between ipsi- and contralateral cortices. Thus, we find no evidence of either receptor loss or receptor supersensitivity. There was, however, a significant decrease in K(+)-stimulated IP formation in the cortex ipsilateral to the damage which probably reflected loss of cholinergic terminals. When comparing the cortex contralateral to NBM damage with the cortex contralateral to sham damage in control rats, no difference was found in any of the above parameters. When severe cognitive deficits are observed, 2-3 weeks after NBM damage, loss of presynaptic ACh is the main change in cortical cholinergic transmission.
Shoham
S
S
Department of Research, Ezrath Nashim Hospital, Jerusalem, Israel.
Newman
M E
ME
Wertman
E
E
Ebstein
R P
RP
D000109:Acetylcholine / Q000378:metabolism; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis / Q000502:physiology; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D015290:Second Messenger Systems / Q000187:drug effects*; D013377:Substantia Innominata / Q000378:metabolism* / Q000473:pathology
D000067956:Adenylyl Cyclase Inhibitors; D007295:Inositol Phosphates; D002217:Carbachol; D010830:Physostigmine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000109:Acetylcholine