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Effects of tacrine (1,2,3,4-tetrahydro-9-aminoacridine) on memory deficits in rats treated with ethylcholine aziridinium ion (AF64A) were studied using active avoidance test in the two-way shuttle box. Neurotoxin AF64A injected at a dose of 6 nmol (icv, bilaterally) causes nonspecific tissue damage in hippocampal fields CA2 and CA3. Two weeks after treatment with 6 nmol, AF64A active avoidance performance of toxin-treated rats was significantly deteriorated compared to vehicle-treated animals estimated in learning test (68±3.5 and 83±3.2% of correct responses, respectively;p<0.01) and in retention test (53±5 and 76±3.6%, respectively;p<0.01). Under these conditions, chronic treatment with tacrine at a daily dose of 1 mg/kg for 12–14 d reverses the effect of AF64A on the active avoidance performance both in learning (78±3.2%) and retention (72±4%) tests. It is supposed that behavioral effects of tacrine considerably depend on a severity of neurodegeneration in the hippocampus.  相似文献   
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Dimebon, a Russian-made drug, inhibited toxic effects of beta -amyloid on cultured neurons. Excessive accumulation of beta-amyloid in the brain is characteristic of Alzheimer dementias. Antialzheimer preparations tacrine and dimebon improve survival of cerebellar granule cells during long-term incubation with Ab25-35, the neurotoxic fragment of beta-amyloid. Both preparations can block potential-dependent Ca2+ entry into neurons by about 20%, which is explained by their selective action on L-type Ca2+ channels. It was assumed that the neuroprotective effect of dimebon and tacrine against Ab25-35 partially depends on inhibition of potential-dependent Ca2+ entry.  相似文献   
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Systemic administration of antihistamine drug dimebon improves active avoidance conditioning in rats with chronic partial deprivation of cerebral cholinergic functions caused by intracerebroventricular injections of AF64A. The effects of dimebon on learning are similar to those of tacrine used in the treatment of Alzheimer's disease. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 6, pp 640–642, June, 2000  相似文献   
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We measured serum content of autoantibodies to -amyloid protein A1-42, its neurotoxic fragment A25-35, vasopressin, bradykinin, thrombin, antithrombin III, 2-macroglobulin, and angiotensin II in patients with various forms of Alzheimer's dementias, including presenile and senile dementias of the Alzheimer type. The ratio of antibradykinin and anti-A1-42 autoantibody contents differed by 39% in these patients. Our results can be used for the development of a new biochemical method for differential diagnostics of dementias of the Alzheimer type.  相似文献   
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Beta-Amyloid peptide fragment 25-35 potentiated phosphate- and calcium-induced opening of mitochondrial channels and caused swelling of mitochondria (even without exogenous calcium and phosphate). These changes were accompanied by accumulation of lipid peroxidation products in mitochondria. Specific inhibitors of mitochondrial channels ADP and cyclosporine A prevented beta-amyloid peptide-induced swelling of mitochondria. Our findings suggest that potentiation of mitochondrial channel opening is an important component of the neurodegenerative effect of beta-amyloid.  相似文献   
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Bulletin of Experimental Biology and Medicine - A model of moderate hyperhomocysteinemia associated with mechanical injury of the musculoskeletal system was developed and experimentally...  相似文献   
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Bulletin of Experimental Biology and Medicine - The prospect of using the antioxidant dipeptide carnosine for the treatment of urate nephrolithiasis was evaluated. Urate nephrolithiasis was modeled...  相似文献   
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