Exendin-4 attenuates brain mitochondrial toxicity through PI3K/Akt-dependent pathway in amyloid beta (1–42)-induced cognitive deficit rats

Publication date: Available online 17 April 2019Source: Neurochemistry InternationalAuthor(s): Debapriya Garabadu, Jaya VermaAbstractAlzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss, disorientation and gradual deterioration of intellectual ability. In the pharmacotherapy of AD, the mitochondrial protective activity of Exendin-4 in experimental studies is yet to be established though its effectiveness is demonstrated in these patients. Therefore, the mitochondria protective activity of Exendin-4 (5 μg/kg, i.p.) was investigated in hippocampus and pre-frontal cortex (PFC) of AD-like animals. The amyloid beta (Aβ) was injected through bilateral intracerebroventricular route into lateral ventricles to induce AD-like manifestations in the male rats. Exendin-4 significantly attenuated Aβ-induced memory-deficits in the Morris water maze and Y-maze test protocols. Exendin-4 significantly decreased Aβ-induced increase in the level of Aβ in both brain regions. Exendin-4 significantly increased Aβ-induced decrease in acetylcholine level and activity of cholineacetyl transferase in all brain regions. Moreover, Exendin-4 significantly decreased Aβ-induced increase in the activity of acetylcholinestrase in both the brain regions. E4 significantly increased Aβ-induced decrease in mitochondrial function, integrity, respiratory control rate and ADP/O in all brain regions. Further, Exendin-4 significantly decreased Aβ-induced increase...
Source: Neurochemistry International - Category: Neuroscience Source Type: research