The relation between serotonergic pathway and depression in an experimental alzheimer's disease model

Alzheimer's disease (AD) is a neurodegenerative disorder that manifests with a decline in cognitive functions accompanied by behavioral alterations and challenges in everyday activities. More than one-third of Alzheimer's patients experience depression. The serotonergic system is an important neurotransmitter system that bridges AD and depression. Male Wistar albino rats were assigned to 4 groups for 4-week-long applications. Control (i.p and oral saline solution), Fluoxetine (i.p. saline solution and 20 mg/kg/day, p.o. Fluoxetine), Alzheimer (10 mg/kg/day, i.p. AlCl3 and 150 mg/kg/day, i.p. D-galactose solution), Alzheimer+Fluoxetine (10 mg/kg/day, i.p. AlCl3 and 150 mg/kg/day, i.p. D-galactose solution + 20 mg/kg/day, p.o. Fluoxetine). All animals were subjected to the Morris water maze test, open-field test, elevated plus maze test, sucrose preference test and forced swim test to evalutate learning/memory, anxiety- and depression-like behaviors. APP, Aβ(1-42), totalTau, phosphoTau, serotonergic receptor, ACTH, CORT, GC and BDNF levels were measured with ELISA. AD model established with AlCl3/D-Gal disturbed learning/memory (p=0.0081) while resulting in depression-like behavior (p=0.0007). Also 5-HT1A (p=0.0028), 5-HT2A (p=0.0002), 5-HT4 (p=0.0036) and 5-HT6 (p=0.0031) levels were found decreased with AD model. Additionally, BDNF levels were decreased (p=0.0345) whereas no statistical significance was found in HPA axis parameters (p>0.05). Flx administration to AD model-established rats improved learning/memory (p=0.0039) and decreased APP (p=0.0097) and Aβ(1-42) (p=0.0418). However, no significance was found in 5-HT1A, 5-HT2A, 5-HT4 and 5-HT6 levels, and BDNF and HPA axis parameters (p>0.05). This study demonstrated that AD and depression under this ground and consequent cognitive deterioration occur with alterations in the serotonin receptor expression. Key words: Alzheimer's disease, Behavior, Depression, Fluoxetine, Serotonergic system.