Sex differences distinguish performance in four object recognition-based memory tasks in the Pink1-/- rat model of Parkinson's disease

Abstract

Many patients with Parkinsons disease (PD) experience early, sometimes prodromal non-motor deficits involving cognition and memory. These so-called mild cognitive impairments hold dire predictions for future risk of freezing, falls and developing PD-related dementia. Moreover, due to a dearth of effective treatments, these symptoms persist and progressively worsen. Thus, there is an urgent need to better understand and better treat these debilitating signs. Sex differences in incidence, severity and treatment sensitivities predict that the answers to these questions are sex-specific. The work presented here highlights new ways in which rats with knockout of PTEN-induced putative kinase 1 gene (Pink1-/-) emulate PDs mild cognitive deficits and their clinical sex differences. Specifically, longitudinal behavioral testing confirmed that male Pink1-/- rats developed significant deficits in Novel Object Recognition and Novel Object Location tasks by 5 months old but that female Pink1-/- were unimpaired in these and the Object-in-Place task through 12 months of age. Further, What, Where, When Episodic-like Memory testing identified enduring deficits in all three memory domains in Pink1-/- males by 3 months of age whereas in Pink1-/- females, non-significant impairments emerged at 7 months of age and progressed to significant memory deficits by 12 months of age. Together, these data show that Pink1-/- rats model the generally greater vulnerability of male PD patients to cognitive and memory deficits in PD, the growing risk for higher order deficits in female patients as they age, and features including early onset that distinguish episodic memory impairments from other at-risk processes in this disorder.