Abstract:Loss of function mutations in PARK6, the gene that encodes the protein PTEN-induced kinase 1 (PINK1), cause autosomal recessive familial Parkinson’s disease (PD). While PD is clinically diagnosed by its motor symptoms, recent studies point to the impact of non-motor symptoms, including cognitive dysfunction in the early pre-motor stages of the disease (Aarsland et al., 2004; Chaudhuri and Schapira, 2009). As the hippocampus is a key structure for learning and memory, this study aimed to determine whether synap… Show more
“…A study using resting-state functional MRI identified reduced connectivity between the neostriatum, midbrain dopaminergic regions, hypothalamus, and thalamus and increased connectivity between the ventral midbrain dopaminergic regions and hippocampus in 6–8-month-old PINK1 −/− rats compared to WT ( Ferris et al, 2018 ; Cai et al, 2019 ). Still, a study measuring hippocampal synaptic plasticity between 4 and 5 months old found no impairment in PINK1 −/− rats compared to controls ( Memon et al, 2021 ). Our study in this PD rat model showed elevated levels of both norepinephrine (NE) and DA in the PFC at a younger age, suggesting the possibility of abnormal DA or NE signaling therein ( Soto et al, 2024 ).…”
Cognitive decline in Parkinson’s disease (PD) is a critical premotor sign that may occur in approximately 40% of PD patients up to 10 years prior to clinical recognition and diagnosis. Delineating the mechanisms and specific behavioral signs of cognitive decline associated with PD prior to motor impairment is a critical unmet need. Rodent PD models that have an impairment in a cognitive phenotype for a time period sufficiently long enough prior to motor decline can be useful to establish viable candidate mechanisms. Arguably, the methods used to evaluate cognitive decline in rodent models should emulate methods used in the assessment of humans to optimize translation. Premotor cognitive decline in human PD can potentially be examined in the genetically altered PINK1−/− rat model, which exhibits a protracted onset of motor decline in most studies. To increase translation to cognitive assessment in human PD, we used a modified non-water multiple T-maze, which assesses attention, cognitive flexibility, and working memory similarly to the Trail Making Test (TMT) in humans. Similar to the deficiencies revealed in TMT test outcomes in human PD, 4-month-old PINK1−/− rats made more errors and took longer to complete the maze, despite a hyperkinetic phenotype, compared to wild-type rats. Thus, we have identified a potential methodological tool with cross-species translation to evaluate executive functioning in an established PD rat model.
“…A study using resting-state functional MRI identified reduced connectivity between the neostriatum, midbrain dopaminergic regions, hypothalamus, and thalamus and increased connectivity between the ventral midbrain dopaminergic regions and hippocampus in 6–8-month-old PINK1 −/− rats compared to WT ( Ferris et al, 2018 ; Cai et al, 2019 ). Still, a study measuring hippocampal synaptic plasticity between 4 and 5 months old found no impairment in PINK1 −/− rats compared to controls ( Memon et al, 2021 ). Our study in this PD rat model showed elevated levels of both norepinephrine (NE) and DA in the PFC at a younger age, suggesting the possibility of abnormal DA or NE signaling therein ( Soto et al, 2024 ).…”
Cognitive decline in Parkinson’s disease (PD) is a critical premotor sign that may occur in approximately 40% of PD patients up to 10 years prior to clinical recognition and diagnosis. Delineating the mechanisms and specific behavioral signs of cognitive decline associated with PD prior to motor impairment is a critical unmet need. Rodent PD models that have an impairment in a cognitive phenotype for a time period sufficiently long enough prior to motor decline can be useful to establish viable candidate mechanisms. Arguably, the methods used to evaluate cognitive decline in rodent models should emulate methods used in the assessment of humans to optimize translation. Premotor cognitive decline in human PD can potentially be examined in the genetically altered PINK1−/− rat model, which exhibits a protracted onset of motor decline in most studies. To increase translation to cognitive assessment in human PD, we used a modified non-water multiple T-maze, which assesses attention, cognitive flexibility, and working memory similarly to the Trail Making Test (TMT) in humans. Similar to the deficiencies revealed in TMT test outcomes in human PD, 4-month-old PINK1−/− rats made more errors and took longer to complete the maze, despite a hyperkinetic phenotype, compared to wild-type rats. Thus, we have identified a potential methodological tool with cross-species translation to evaluate executive functioning in an established PD rat model.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.