Effect of vagal autotransplantation and bifemelane hydrochloride on cholinergic markers and event-related potentials in rats with lesions of the nucleus basalis magnocellularis.
In rats lesioned by injecting the ibotenic acid (8 micrograms/site) into the unilateral nucleus basalis magnocellularis (NBM), the effect of treatment with bifemelane hydrochloride (BIF) or autotransplantation of the vagal nodosal ganglion was studied electrophysiologically by serial measurement of the event-related potential (ERP, P300) for 4 weeks. In addition, the effects on cholinergic markers were assessed by determining the specific binding of [3H]QNB (quinuclidinyl benzilate) to the muscarinic acetylcholine receptor (mAChR) as well as the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE). The P300 latency was delayed and its amplitude remained low for 4 weeks in NBM-lesioned rats. In contrast, a return to normal occurred after 2-3 weeks in rats given daily intraperitoneal injections of BIF (15 mg/kg) and in autotransplanted rats. In lesioned rats, the cortical ChAT and AChE activities on the affected side did not recover, but the postsynaptic receptor response was transiently activated soon after lesioning. BIF increased specific mAChR binding (an early increase of affinity and a subsequent increase of receptor density) as well as presynaptic ChAT activity. Transplantation achieved the early activation of mAChR binding (increased receptor density) and continuously increased ChAT activity. Thus, the postsynaptic compensatory receptor mechanism of denervation supersensitivity acted as an early response to the depression of presynaptic cholinergic activity, but it could not improve the P300 response until the subsequent increase of cortical ChAT activity. Improvement of P300 combined with cortical cholinergic recovery after nodosal ganglion grafting or administration of BIF suggests that the neocortical ACh level may play an important role in regulating ERP.
Department of Neurosurgery, Kanazawa University School of Medicine, Japan.
K
K
Ikeda
T
T
Egashira
J
J
Yamashita
S
S
Okoyama
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D015415:Biomarkers / Q000737:chemistry; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D006651:Histocytochemistry; D008297:Male; D009620:Nodose Ganglion / Q000637:transplantation*; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects; D013377:Substantia Innominata / Q000187:drug effects* / Q000378:metabolism; D014182:Transplantation, Autologous
D001559:Benzhydryl Compounds; D015415:Biomarkers; D011976:Receptors, Muscarinic; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine; C031906:bifemelane