Abstract
In the current study, we investigated the protective role of citalopram against cognitive decline, impaired mitochondrial dynamics, defective mitochondrial biogenesis, defective autophagy, mitophagy and synaptic dysfunction in APP transgenic mouse model of Alzheimer's disease (ad). We treated 12-month-old wild-type (WT) and age-matched transgenic APP mice with citalopram for 2months. Using Morris Water Maze and rotarod tests, quantitative RT-PCR, immunoblotting, biochemical methods and transmission electron microscopy methods, we assessed cognitive behavior, RNA and protein levels of mitochondrial dynamics, biogenesis, autophagy, mitophagy, synaptic, ad-related and neurogenesis genes in wild-type and APP mice treated and untreated with citalopram. Citalopram-treated APP mice relative to citalopram-untreated APP mice exhibited improved cognitive behavior. Increased levels of mRNA associated with mitochondrial fission and ad-related genes; decreased levels of fusion, biogenesis, autophagy, mitophagy, synaptic and neurogenesis genes were found in APP mice relative to WT mice. However, APP mice treated with citalopram compared to citalopram-untreated APP mice revealed reduced levels of the mitochondrial fission and ad-related genes and increased fusion, biogenesis, autophagy, mitophagy, synaptic and neurogenesis genes. Our protein data agree with the mRNA levels. Transmission electron microscopy revealed significantly increased mitochondrial numbers and reduced mitochondrial length in APP mice; these were reversed in citalopram-treated APP mice. Further, Golgi-cox staining analysis revealed reduced dendritic spines in APP mice relative to WT mice. However, citalopram-treated APP mice showed significantly increased dendritic spines, indicating that citalopram enhances spine density, synaptic activity and improved cognitive function in APP mice. These findings suggest that citalopram reduces cognitive decline, Aβ levels and mitochondrial and synaptic toxicities and may have a strong protective role against mutant APP and Aβ-induced injuries in patients with depression, anxiety and ad.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.