Related Experiment Video
Updated: Sep 14, 2025
Novel Object Recognition Test for the Investigation of Learning and Memory in Mice
Published on: August 30, 2017
Sex differences distinguish performance in four object recognition-based memory tasks in the Pink1-/- rat model of
Aveena M Desai1, Oluwagbohunmi A Aje1, Mary F Kritzer1
1Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, New York, 11794-5230, USA.
Abstract:
Male more than female patients with Parkinson's disease (PD) experience early, sometimes prodromal non-motor deficits involving cognition and memory. These so-called mild impairments predict future risk of freezing, falls and developing PD-related dementia. Moreover, because most treatments are ineffective, these symptoms often persist and progressively worsen. Thus, there are urgent needs to better understand and better treat these signs. The work presented here highlights new ways in which rats with knockout of PTEN-induced putative kinase 1 gene (Pink1-/-) can serve as models that emulate PD's mild cognitive deficits and their 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 in the Object-in-Place task through testing at 12 months of age. Further, What, Where, When Episodic-like Memory testing showed that deficits in all three memory domains were present in Pink1-/- males by 3 months of age. However, in Pink1-/- females, non-significant episodic memory impairments were first observed at 7 months of age which progressed to significant deficits in 'What', 'Where' and 'When' domains by the time female rats were 12 months old. Together, these data show that Pink1-/- rats model the greater vulnerability of male PD patients to cognitive and memory deficits; the increasing risk for higher-order deficits in female PD patients with age; and other features including the early/earliest onset that distinguishes episodic memory impairments from other at-risk cognitive operations in this disorder.
Insights
Male Parkinson's disease (PD) patients show early cognitive deficits. Pink1 knockout rats mirror these sex differences, with males exhibiting early memory impairments while females develop them later with age.
Area of Science:
- Neuroscience
- Genetics
- Animal Models
Background:
- Male Parkinson's disease (PD) patients often experience early cognitive and memory deficits.
- These non-motor symptoms can precede motor symptoms and predict dementia, with limited treatment options.
- Understanding the biological basis and sex differences in these early deficits is crucial.
Purpose of the Study:
- To investigate the utility of PTEN-induced putative kinase 1 gene knockout (Pink1-/-) rats as a model for PD-related cognitive and memory deficits.
- To examine sex differences in cognitive and memory impairments in Pink1-/- rats.
- To characterize the temporal progression of these deficits in the model.
Main Methods:
- Longitudinal behavioral testing of male and female Pink1-/- rats.
- Assessment of cognitive functions including Novel Object Recognition, Novel Object Location, and Object-in-Place tasks.
- Evaluation of episodic-like memory using What, Where, When tasks at various ages.
Main Results:
- Male Pink1-/- rats showed significant deficits in recognition and location memory by 5 months of age.
- Female Pink1-/- rats remained unimpaired in these tasks until 12 months of age.
- Episodic-like memory deficits appeared earlier (3 months) in males than females (7-12 months), with 'What', 'Where', and 'When' domains affected.
Conclusions:
- Pink1-/- rats effectively model the sex differences observed in PD cognitive deficits, with males showing earlier onset.
- The model captures the age-dependent progression of cognitive impairments in female PD patients.
- This model provides insights into the early onset of episodic memory impairments in Parkinson's disease.
