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Chronic decreases in brain cholinergic functions due to intraventricular administration of the neurotoxin AF64A were accompanied by increases in the latent period of locating an invisible platform during training of rats in a Morris water test, as compared with control sham-operated animals. Recordings of the animals' movement trajectories using a video camera along with an original computer program (Behavioral Vision) showed that administration of 17beta-estradiol and its synthetic analog J-861 (0.2 mg/kg p.o. daily for seven days before and 10 days after single intraventricular injections of AF64A) improved learning. The directivity of platform search trajectories was assessed quantitatively using a new parameter--trajectory straightness. Introduction of the "passive swimming" parameter allowed periods of immobility in water to be identified within the total latent period in animals after administration of AF64A; 17beta-estradiol but not J-861 "eliminated" these periods. The new parameters (especially trajectory straightness) allowed the ability to learn to be discriminated from decreases in mobility, including mobility losses due to study agents, in the Morris water test.

We measured serum content of autoantibodies to β-amyloid protein Aβ1-42, its neurotoxic fragment Aβ25-35, vasopressin, bradykinin, thrombin, antithrombin III, α2-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-Aβ1-42 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.

Systemic oral administration of NT-0409, a new synthetic agonist of AMPA subtype glutamate receptor, to rats with chronic partial AF64A-induced deprivation of cholinergic functions improved their learning in a Morris water maze. NT-0409 is close to memantine by the effect on learning and, in contrast to cholinomimetic arisept, ensures longer retention of the developed habit.

Survival of neuronal ganglia from newborn snail (Helix aspera L.) in the brain of adult rats was studied. Snail ganglion survived in the brain of warm-blooded animals for 6 months without inducing immune conflict. At early stages (5 days) after transplantation, xenografts increased in size and were several times larger than native ganglia from 10-day-old snails, thereafter (on days 28 and 180) they became smaller still surpassing the sizes of ganglia from snail of the corresponding age. Rapid enlargement of the xenograft was due to cell reactive processes in the ganglion. Deep penetration of large vessels from xenografts to rat brain was observed.

The content of autoantibodies to β-amyloid protein Aβ1-42, its neurotoxic fragment Aβ25-35, and neurotransmitters were studied in the blood of patients with presenile Alzheimer's disease and senile dementia of the Alzheimer type. Significant differences in the relative content of autoantibodies to Aβ1-42 and autoantibodies to biogenic amines were demonstrated. These results can be used for the development of a biochemical method for differential diagnosis of Alzheimer dementias.

Possibility of ortho-, para-, meta-methylphenyl and methoxyphenyl-derivates of MPTP to produce parkinsonism was investigated. Only ortho-methylphenyl- and ortho-methoxyphenyl-derivates of MPTP cause a persistent loss in dopamine content in the brain and produced the clinical symptoms of parkinsonism. All substances produced Parkinsonian-like syndrome gives the symptoms of activation of nervous system during 0.5-1 h after injection and symptoms of depression in following 3 h of observations.

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.

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.

It was shown for the first time that estrogens 17 beta- and 17 alpha-estradiols compensate impaired cognitive functions in rats with partial chronic deprivation of cholinergic functions in the central nervous system induced by intracerebral administration of selective cholinergic neurotoxin AF64A. 17 beta-Estradiol produced strong dose-dependent changes in the weights of hormone-sensitive endocrine glands, while 17 alpha-estradiol did not affect the weight of the gonads and slightly influenced (in high concentration) the weights of the adrenal glands and thymus. The positive effects of exogenous 17 beta- and 17 alpha-estradiols on cognitive functions are due to their antioxidant properties, rather than due to specific action on hormone-sensitive endocrine glands.

The neurotoxic actions of MPTP and its 4-(O-tolyl) analog (2′-Me-MPTP) on two breeds of rabbits were investigated. MPTP, but not 2′-Me-MPTP, causes a reduction (about 40%) in striatal dopamine content in rabbits of the “little silver-black” breed. The dopamine content of striata of “chinchilla” rabbits was not affected by either agent.

Effects of tacrine (1,2,3,4-tetrahydro-9-aminocridine) 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 (i.c.v., 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; p0.01) and in retention test (53 +/- 5 and 76 +/- 3.6%, respectively; p0.01). 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.