Abstract
Parkinson’s disease (PD) is associated with a large burden of non-motor symptoms including olfactory and autonomic dysfunction, as well as neuropsychiatric (depression, anxiety, apathy) and cognitive disorders (executive dysfunctions, memory and learning impairments). Some of these non-motor symptoms may precede the onset of motor symptoms by several years, and they significantly worsen during the course of the disease. The lack of systematic improvement of these non-motor features by dopamine replacement therapy underlines their multifactorial origin, with an involvement of monoaminergic and cholinergic systems, as well as alpha-synuclein pathology in frontal and limbic cortical circuits. Here we describe mood and neuropsychiatric disorders in PD and review their occurrence in rodent models of PD. Altogether, toxin-based rodent models of PD indicate a significant but non-exclusive contribution of mesencephalic dopaminergic loss in anxiety, apathy, and depressive-like behaviors, as well as in learning and memory deficits. Gene-based models display significant deficits in learning and memory, as well as executive functions, highlighting the contribution of alpha-synuclein pathology to these non-motor deficits. Collectively, neuropsychiatric and cognitive deficits are recapitulated to some extent in rodent models, providing partial but nevertheless useful options to understand the pathophysiology of non-motor symptoms and develop therapeutic options for these debilitating symptoms of PD.
Highlights
Parkinson’s disease (PD), one of the most frequent neurodegenerative diseases, is characterized by motor symptoms including akinesia, bradykinesia, tremor, rigidity, and postural instability, and by several debilitating non-motor symptoms (NMS) that may precede motor dysfunctions by several years
A recent review highlights that functional neuroimaging studies reveal that anxiety is associated with changes in limbic cortico-striato-thalomocortical circuits that are significantly affected by the disease process, accounting for a high prevalence of anxiety in PD patients [23]
Dementia is defined as a complex NMS, occurring when the neuropsychological profile of patients is impaired in several cognitive domains
Summary
Parkinson’s disease (PD), one of the most frequent neurodegenerative diseases, is characterized by motor symptoms including akinesia, bradykinesia, tremor, rigidity, and postural instability, and by several debilitating non-motor symptoms (NMS) that may precede motor dysfunctions by several years This prodromal phase may last 20 years or more [1] depending on clinical considerations. During this period and the development of PD, various NMS, often misdiagnosed, occur such as olfactory dysfunction (hyposmia, anosmia), gastro-intestinal disorders (constipation), sleep disorders, neuropsychiatric disorders (depression, anxiety and apathy) and cognitive dysfunction (executive dysfunctions, memory and learning impairments) [2,3]. Biomedicines 2021, 9, 684 olfactory dysfunction can be found in the review by Chesselet et al in the same issue of Biomedicines
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