Protective effects of SSRI, Citalopram in mutant APP and mutant Tau expressed dorsal raphe neurons in Alzheimer's disease

Biochim Biophys Acta Mol Basis Dis. 2023 Nov 4:166942. doi: 10.1016/j.bbadis.2023.166942. Online ahead of print.ABSTRACTDepression is among the most common neuropsychiatric comorbidities in Alzheimer's disease (AD) and other Tauopathies. Apart from its anti-depressive and anxiolytic effects, selective serotonin reuptake inhibitor (SSRI) treatment also offers intracellular modifications that may help to improve neurogenesis, reduce amyloid burden & Tau pathologies, and neuroinflammation in AD. Despite its multifaceted impact in the brain, the exact physiological and molecular mechanism by which SSRIs such as Citalopram improve neurogenesis and synaptogenesis in dementia is poorly understood. In the current study, we investigated the protective role of SSRI, Citalopram, in serotonergic, medullary raphe neurons (RN46A-B14). RN46A-B14 cells were transfected with wild-type and mutant APP and Tau cDNAs for 24 h and then treated with 20 μM Cit for 24 h. We then assessed mRNA and protein levels of p-Tau, total Tau, serotonin related proteins such as TPH2, SERT, and 5HTR1a, synaptic proteins and cytoskeletal structure. We also assessed cell survival, mitochondrial respiration and mitochondrial morphology. The mutant APP and Tau transfected cells showed increased levels of serotonin related proteins and mRNA, while the mRNA and protein levels of synaptic proteins were downregulated. Citalopram treatment significantly reduced pathologically p-Tau level along with the serotonin rela...
Source: Biochimica et Biophysica Acta - Category: Biochemistry Authors: Source Type: research