[Protective action of glutamate antibodies on increased expression of genes of programmed death of rat brain cells induced by injection of a ß-amyloid fragment (25-35)].

Glutamate antibodies intranasally administered to Wistar rats at a dose of 300 µg/kg reduced the elevated levels of expression of Aifml, Casp3, and Parp 1 genes in the prefrontal cortex and Aifml and Casp3 genes in the hippocampus on the third day after administration of the ß-amyloid fragment Aß25-35 into the Meynert nuclei of the brain. Changes in Aifm1, Bax, Casp3, and Parp 1 gene expression were not found in the hypothalamus, and changes in Bax gene expression were not found in the brain structures studied. The discovered features of gene expression in the prefrontal cortex and hippocampus are considered in terms of development of various cell-death programs, which are modulated by glutamate antibodies.

[Comparison of the effects of glutamate antibodies on neuronal activity of caspase 3 and memory impairment in rats induced by injection of Abeta(25-35) into the Meynert nuclei].

In experiments on rats showed that intranasal administration of glutamate antibodies in a dose of 300 microg/kg after 1 h after bilateral injection of neurotoxic fragment of beta-amyloid protein (25-35)--Abeta(25-35)--into the Meynert nuclei restores learning ability in the test of passive avoidance on 3 and 14 days of the experiment. Antibodies to glutamate decrease significantly increasing caspase 3 activity, detected on Day 3 after injection of Abeta(25-35), in samples of the prefrontal cortex and hippocampus but not hypothalamus. Intranasal administration of gamma-globulin had no effect on the performance of violations of mnestic functions and caspase 3 activity.

Effect of antibodies to glutamate on caspase-3 activity in brain structures of rats with experimental Alzheimer's disease.

Experiments on rats have showed that neurodegenerative damage to the brain induced by injection of a neurotoxic ß-amyloid protein fragment ß25-35into the basal giant cell nuclei of Meynert activated caspase-3 in the prefrontal cortex and hippocampus on day 3 after injury. Intranasal administration of antibodies to glutamate in a dose of 300 µ g/kg 1 h after damage reduced enzyme activity in these structures in a rat model of Alzheimer's disease.

[Repressional effects of the glutamate antibodies on expression of Dffb gene in the brain of rats with experimental Alzheimer's disease].

The intranasal administration of glutamate antibodies in the dose of 300 microg/kg one hour after damage on the level of mRNA expression of Dffb gene which codes caspase-activated DNase which participates in intranucleosome fragmentation of genome DNA in apoptosis was investigated in experimental Alzheimer's disease induced by injection of neurotoxic fragment of beta-amyloid protein Abeta25-35 in Meynert basal magnocellular nuclei on rats. On the Day 3 after Abeta25-35 injection is observed significant decrease of the level of mRNA expression of Dffb gene in prefrontal cortex in 37%, and in hippocampus in 62% in the experiment group versus the control group. These differences were not found in the hypothalamus when comparing the experimental and control animals. It was suggested that repressive effect of glutamate antibodies on the level of mRNA expression of Dffb gene reflects stabilization of processes taking place in brain cells in experimental Alzheimer's disease, and in its turn the intensiveness of nerve and glial cells apoptotic death is decreased.

Regional features of the expression of genes involved in neurogenesis and apoptosis in the brain of adult rats.

The expression of mRNA of genes involved in neurogenesis and apoptosis (Apaf1, Ascl1, Bax, Bcl2, Casp3, Casp8, Casp9, Dffb, Myh10, Naip2, Napa, Notch2, Numb, Pura, S100a6, Tnf) in the prefrontal cortex, hippocampus, and cerebellum was studied in adult rats. The content of mRNA of these genes (except Apaf1) was several-fold higher in the cerebellum than in the hippocampus and brain cortex. In the hippocampus, the expression of Apaf1 was significantly lower than in the prefrontal cortex, while the expression of Ascl1, Pura, S100b, and Tnf was higher. Regional differences in the direction, strength, and numbers of significant correlations between the expression of the studied genes were detected. Documented differences in gene expression were regarded as validation of the structural and functional cooperation of neurogenesis and apoptosis at the molecular genetic level.