Serotonin circuit dysregulation in Alzheimer’s Disease
Project Overview
The early and severe loss of serotonin neurons along with the neuroprotective effects of SSRIs in Alzheimer’s Disease (AD) strongly implicates the serotonin system in disease pathology. Yet, mechanisms underlying the vulnerability and contribution of the serotonin system to AD progression remain unknown. Serotonergic impairment early in disease process is thought to underlie the behavioral symptoms in AD. A major risk factor is severe stress experienced early in life, which also disrupts the maturation of serotonin circuits. We hypothesize that serotonergic dysfunction early in AD progression disrupts brain-wide connectivity of the serotonin system, contributing to preclinical behavioral symptoms. We will examine the activity and connectivity of serotonin neurons in an AD mouse model. We will determine how early life stress-induced impairments in the serotonin system affect disease progression and utilize optogenetics to stimulate serotonin circuits to improve behavioral function.
Principal Investigator
Derya Sargin , University of Calgary
Partners and Donors
Alzheimer's Association