Nurr1 knockout in substantia nigra proposed to result in cognitive deficits in Rattus norvegicus

Abstract

Many Parkinson's disease (PD) patients suffer from cognitive impairment. Reduced secretion of dopamine (DA) from substantia nigra (SN) to striatum results in motor deficits in PD patients, but little is known about its effects on cognition. Nurr 1 is a nuclear receptor expressed in SN neurons and regulates DA expression. The role of Nurrl in PD-related cognitive deficits has not yet been studied. We hypothesize that reduced levels of Nurrl in the SN, leading to decreased DA in striatum, will result in cognitive deficits in Rattus norvegicus. Knockdown of Nurrl in SN with an anti-Nurrl ribozyme was unsuccessful. CRISPR/Cas9 will be used to knockout Nurrl before performing cognitive and behavioral testing to help reveal the role of Nurrl in the cognitive behavior of PD patients and potentially implicate overexpression of Nurrl as a treatment for cognitive impairments.