Septal choline acetyltransferase immunoreactive neurons: dose-dependent effects of AF64A.
Two experiments were performed. In the first, the cholinotoxin, AF64A (0.5, 1.0 or 1.5 nmol/ventricle), or vehicle (3.0 microliters) was injected (ICV) bilaterally into male rats (n = 23). Choline acetyltransferase (ChAT) immunoreactive (IR) perikarya in the four subgroups of the septal complex were visualized by immunocytochemistry (PAP method) 28 days postinjection, and counted using a microprojector (x40). The 0.5 nmol/ventricle dose of AF64A significantly reduced (31%) the number of ChAT-IR cell bodies in the intermediate subgroup (rostral extension of the nucleus basalis/substantia innominata). Higher doses did not produce additional reductions. The highest dose (1.5 nmol/ventricle) of AF64A resulted in significant decreases in ChAT-IR cell bodies in the dorsal (51%) and midline (35%) subgroups (medial septum), but did not affect the number of ventral subgroup (diagonal band of Broca) ChAT-IR neurons. In the second experiment, electrolytic lesions were placed in the corpus callosum, cingulum and overlying cingulate gyrus, in order to simulate the nonselective damage seen following the 1.5 nmol/ventricle dose of AF64A. In comparison to the surgical controls (n = 3), the electrolytic lesions (n = 6) failed to significantly affect the number of ChAT-IR perikarya in any of the septal subdivisions. Thus the distinct subgroups of septal ChAT-IR neurons are differentially sensitive to the toxic effects of ICV administered AF64A: intermediate much greater than dorsal greater than midline much greater than ventral subgroup.
Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago Stritch School of Medicine, Maywood, IL 60153.
S A
SA
Lorens
G
G
Kindel
X W
XW
Dong
J M
JM
Lee
I
I
Hanin
D000818:Animals; D001388:Aziridines / Q000494:pharmacology*; D001921:Brain / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D002794:Choline / Q000031:analogs & derivatives* / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000032:analysis / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values
D001388:Aziridines; D009498:Neurotoxins; C044894:ethylcholine aziridinium; D002795:Choline O-Acetyltransferase; D002794:Choline