[Study on the anti-dementia therapies for rats with a unilateral basal forebrain lesion--serial changes of the cholinergic markers' activities and event-related potentials after the administration of bifemelane hydrochloride or autotransplantation of the vagal nodosal ganglion].
Using rats with a unilateral lesion in the nucleus basalis magnocellularis (NBM), we examined electrophysiologically the therapeutic effects of bifemelane (BIF) and autotransplantation of the vagal nodosal ganglion (X) on the event-related potential (P300) serially for 4 weeks, and also neurochemically their effects on cholinergic markers--the specific binding of 3H-QNB (quinuclidinyl benzilate) on muscarinic acetyl-choline receptor (mAChR) and the activities of acetylcholinesterase (AChE) and choline acetyltransferase (CAT). The latency of P300 was continuously delayed and its amplitude remained low voltage until 4 weeks in the NBM-lesioned rats (No-Tx group). Whereas the latency and amplitude returned to normal after 2-3 weeks in the rats given daily intraperitoneal injection of 15 mg/kg BIF (BIF group) and autotransplanted ones (X group). The cortical CAT and AChE levels on the lesion side did not recover until 4 weeks in No-Tx group, but the CAT levels recovered after 3 weeks in both BIF and X group; the AChE levels, after 1 week in BIF group and after 3 weeks in X group. The cortical mAChR on the lesion side was within or more than normal range in all rats. These results might indicate as follows: 1) Compensatory postsynaptic process such as cortical mAChR increase and AChE decrease occurred after acute cholinergic depletion. 2) Administration of BIF and X autotransplantation recovered cortical CAT and AChE levels and normalized cholinergic neuronal activity of P300.
Ikeda
K
K
Department of Neurosurgery, Kanazawa University School of Medicine, Japan.
Yamashita
J
J
Egashira
T
T
Takayama
F
F
Yamanaka
Y
Y
D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D001927:Brain Diseases / Q000150:complications; D002795:Choline O-Acetyltransferase / Q000032:analysis; D003704:Dementia / Q000209:etiology / Q000628:therapy*; D005071:Evoked Potentials / Q000187:drug effects; D008297:Male; D016548:Prosencephalon; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism; D014182:Transplantation, Autologous; D014630:Vagus Nerve / Q000637:transplantation*
D001559:Benzhydryl Compounds; D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; C031906:bifemelane