Task-specific effects of biological sex and sex hormones on object recognition memories in a 6-hydroxydopamine-lesion model of Parkinson’s disease in adult male and female rats

Pinizzotto, Claudia C.; Patwardhan, Aishwarya; Aldarondo, Daniel; Kritzer, Mary F.

doi:10.1101/2022.02.15.480556

Cited by 2 publications

References 152 publications

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Systematic review of rodent studies of deep brain stimulation for the treatment of neurological, developmental and neuropsychiatric disorders

Zhang,

Matin,

Gorodetsky

et al. 2024

Transl Psychiatry

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Deep brain stimulation (DBS) modulates local and widespread connectivity in dysfunctional networks. Positive results are observed in several patient populations; however, the precise mechanisms underlying treatment remain unknown. Translational DBS studies aim to answer these questions and provide knowledge for advancing the field. Here, we systematically review the literature on DBS studies involving models of neurological, developmental and neuropsychiatric disorders to provide a synthesis of the current scientific landscape surrounding this topic. A systematic analysis of the literature was performed following PRISMA guidelines. 407 original articles were included. Data extraction focused on study characteristics, including stimulation protocol, behavioural outcomes, and mechanisms of action. The number of articles published increased over the years, including 16 rat models and 13 mouse models of transgenic or healthy animals exposed to external factors to induce symptoms. Most studies targeted telencephalic structures with varying stimulation settings. Positive behavioural outcomes were reported in 85.8% of the included studies. In models of psychiatric and neurodevelopmental disorders, DBS-induced effects were associated with changes in monoamines and neuronal activity along the mesocorticolimbic circuit. For movement disorders, DBS improves symptoms via modulation of the striatal dopaminergic system. In dementia and epilepsy models, changes to cellular and molecular aspects of the hippocampus were shown to underlie symptom improvement. Despite limitations in translating findings from preclinical to clinical settings, rodent studies have contributed substantially to our current knowledge of the pathophysiology of disease and DBS mechanisms. Direct inhibition/excitation of neural activity, whereby DBS modulates pathological oscillatory activity within brain networks, is among the major theories of its mechanism. However, there remain fundamental questions on mechanisms, optimal targets and parameters that need to be better understood to improve this therapy and provide more individualized treatment according to the patient’s predominant symptoms.

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Systematic review of rodent studies of deep brain stimulation for the treatment of neurological, developmental and neuropsychiatric disorders

Zhang,

Matin,

Gorodetsky

et al. 2024

Transl Psychiatry

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Spontaneous object exploration in a recessive gene knockout model of Parkinson’s disease: Development and progression of object recognition memory deficits in male Pink1-/- rats

Pinizzotto

Dreyer

Aje

et al. 2022

Preprint

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Cognitive impairments appear at or before motor signs in about one third of patients with Parkinson’s disease (PD) and have a cumulative prevalence of roughly 80% overall. These deficits exact an unrelenting toll on patients’ quality and activities of daily life due in part to a lack of available treatments to ameliorate them. This study used three well-validated novel object recognition-based paradigms to explore the suitability of rats with knockout of the PTEN-induced putative kinase1 gene (Pink1) for investigating factors that induce cognitive decline in PD and for testing new ways to mitigate them. Longitudinal testing of rats from three to nine months of age revealed significant impairments in male Pink1-/- rats compared to wild type controls in Novel Object Recognition, Novel Object Location and Object-in-Place tasks. Task-specific differences in the progression of object discrimination/memory deficits across age were also seen. Finally, testing using an elevated plus maze, a tapered balance beam and a grip strength gauge showed that in all cases recognition memory deficits preceded potentially confounding impacts of gene knockout on affect or motor function. Taken together, these findings suggest that knockout of the Pink1 gene negatively impacts the brain circuits and/or neurochemical systems that support performance in object recognition tasks. Further investigations using Pink1-/-rats and object recognition memory tasks should provide new insights into the neural underpinnings of the visual recognition memory and visuospatial information processing deficits that are often seen in PD patients and accelerate the pace of discovery of better ways to treat them.

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Task-specific effects of biological sex and sex hormones on object recognition memories in a 6-hydroxydopamine-lesion model of Parkinson’s disease in adult male and female rats

Cited by 2 publications

References 152 publications

Systematic review of rodent studies of deep brain stimulation for the treatment of neurological, developmental and neuropsychiatric disorders

Systematic review of rodent studies of deep brain stimulation for the treatment of neurological, developmental and neuropsychiatric disorders

Spontaneous object exploration in a recessive gene knockout model of Parkinson’s disease: Development and progression of object recognition memory deficits in male Pink1-/- rats

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