Fluoxetine rescues impaired hippocampal neurogenesis in a transgenic A53T synuclein mouse model

摘要: The accumulation of alpha-synuclein in Lewy bodies and neurites different neuronal populations is one the neuropathological hallmarks Parkinson disease (PD). Overexpression human wildtype or mutant affects generation new neurons adult dentate gyrus (DG) hippocampus models PD. Hippocampal dysfunction with reduced neurogenesis plays an important role pathogenesis depression, non-motor symptom Moreover, effective antidepressant treatment still unmet need present study explored if impaired hippocampal A53T transgenic animal model PD may be restored by chronic oral application selective serotonin reuptake inhibitor (SSRI) fluoxetine. First, we determined expression pattern synuclein developing DG showed early transgene linked to a severely neurogenesis. After fluoxetine observed increased more than threefold treated mice compared controls. pro-neurogenic effect predominantly related proliferation neural precursor cells DG, lesser extent induction differentiation into mature neurons. Analysis underlying mechanisms revealed brain-derived glial cell-derived neurotrophic factor levels as result treatment. This underlines large potential SSRI-dependent stimulate lead novel means improve neuropsychiatric symptoms