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Limitations of the rat medial forebrain lesion model to study prefrontal cortex mediated cognitive tasks in Parkinson’s disease
Journal article   Peer reviewed

Limitations of the rat medial forebrain lesion model to study prefrontal cortex mediated cognitive tasks in Parkinson’s disease

Courtney A. Marshall, Kirsten M. King and Sandhya Kortagere
Brain research, v 1702, pp 105-113
01 Jan 2019
PMID: 29608880

Abstract

Medial forebrain bundle lesion Mild cognitive impairment Novel object recognition task Parkinson’s disease Prefrontal cortex Set shifting task
•A 6-OHDA induced medial forebrain bundle lesion rodent model of Parkinson’s Disease (PD): Produces stable and robust motor impairment in rodents.•Impairments in the simple discrimination task of attentional set shifting paradigm.•Produces temporal order memory deficits, but not in spatially-driven object recognition task.•No difference between male and female rats in cognitive flexibility and memory tasks.•Does not recapitulate the PFC-mediated cognitive deficits observed in PD patients. Parkinson’s Disease (PD) is a progressive movement disorder characterized by the loss of dopaminergic neurons in the midbrain. Besides motor impairment, PD patients exhibit non-motor symptoms that negatively impact their quality of life and often manifest prior to motor deficits. One such symptom is mild cognitive impairment (PD-MCI), which is comprised of deficits in executive function such as working memory, attention, cognitive flexibility, and spatial memory. The 6-hydroxydopamine (6-OHDA) induced unilateral medial forebrain bundle (MFB) lesion animal model successfully recapitulates PD motor impairment but is also used to assess non-motor deficits. The present study utilizes a unilateral 6-OHDA induced MFB lesion rodent model to investigate prefrontal cortex (PFC)-mediated cognitive processes that are impaired in PD patients. In a test of attentional set shifting, PD rodents demonstrated deficits in simple discrimination, but not in rule reversal or extradimensional shifts. PD rodents also exhibited deficits in a temporal order memory task but had no deficits in novel/spatial object recognition or object-in-place tasks. These results reveal limitations of the 6-OHDA induced unilateral MFB lesion model to completely recapitulate PD-MCI symptoms suggesting a need for better lesion models to study PD-MCI.

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