Журнал болезни Альцгеймера и паркинсонизма

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Response of �?±-Synuclein Expression to Amyloid �?²40 and Amyloid �?²42 administration into Rat Brain

Mishra N, Kumar P, Singh R1 and Sharma D

Objective: In the present study, we assessed the change in α-synuclein expression upon stereotaxic administration of pre-aggregated amyloid (Aβ40 and Aβ42) in the hippocampus and amygdala of the rat brain.

Method: Forty-eight, male Wistar rats, 6 months of age at the beginning of the experiment, were divided into 8 groups, containing 6 animals in each group. Group 1: saline injected into the hippocampus (Aβ40 Hippocampus Control). Group 2: aggregated-Aβ40injected into the hippocampus (Aβ40 Hippocampus Test). Group 3: saline injected into the amygdala (Aβ40 Amygdala Control). Group 4: aggregated-Aβ40 injected into the amygdala (Aβ40 Amygdala Test). Group 5: 16.7%DMSO in distilled water injected into the hippocampus (Aβ42 Hippocampus Control). Group 6: aggregated-Aβ42 oligomer was injected into the hippocampus (Aβ42 Hippocampus Test). Group 7: 16.7%DMSO in distilled water injected into the amygdala (Aβ42 Amygdala Control). Group 8: aggregated-Aβ42 administered into the amygdala (Aβ42Amygdala Test). Animals of each group were sacrificed by cervical dislocation (n=6) and transcardial perfusion (n=4) for molecular experiments (real-time PCR and western blotting) and histological studies, respectively. Brains were micro-dissected into amygdala, hippocampus, cortex, cerebellum, medulla, and midbrain for the molecular experiments.

Results: We found that there was an increase in the expression of α-synuclein, both at the gene and protein levels, in the hippocampus and cortex of the amyloid injected animals. Aβ42 seemed to produce a quantitatively greater effect than Aβ40.

Conclusion: Therefore, it can be extrapolated that increased expression of amyloid precursor protein (APP) gene can lead to the increase in expression of α-synuclein, leading to greater neurotoxicity in neurodegenerative disorders caused by APP overexpression (such as AD).