Depression 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 pTau, total Tau,
serotonin related
proteins such as TPH2, SERT, and 5HTR1a, synaptic
proteins and the 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 pTau level along with the
serotonin related
protein levels. On the other hand, there was a significant increase in the
mRNA and
protein levels of synaptic genes and cytoskeletal structure in the treated groups. Further,
Citalopram also improved cell survival, mitochondrial respiration and mitochondrial morphology in the treated cells that express mAPP and mTau. Taken together these findings suggest
Citalopram could not only be a promising therapeutic
drug for treating patients with depression, but also for AD patients.