Cholinergic systems, attentional-motor integration, and cognitive control in Parkinson's disease

Albin, Roger L.; Zee, Sygrid van der; Laar, Teus van; Sarter, Martin; Lustig, Cindy; Müller, Martijn; Bohnen, Nicolaas I.

doi:10.1016/bs.pbr.2022.01.011

Cited by 20 publications

(12 citation statements)

References 103 publications

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“…Our finding showed that the presence of freezing gait was associated with atrophy in Ch4 and the degree of Ch4 atrophy increased with the deterioration of freezing gait. We speculated that the degeneration and dysfunction of cholinergic systems caused by Ch4 atrophy could lead to the diminished capacity to allocate attention and reduced ability to process distractors, thus heightening gait disturbance 44 . Our study indicated the pivotal role of this region in the pathogenesis of PD‐FOG to some extent.…”

Section: Discussionmentioning

confidence: 60%

“…Experimental evidence on animal models and humans showed a strong relationship between loss of cholinergic neurons and attention impairments 43 . Normal attentional functions are necessary for maintenance balance and normal gait performance 44 . It was proposed that the dopaminergic degeneration brings about gait automaticity loss, thus demanding more constant attention, thereby increasing more dependence of higher‐order systems of gait on the cholinergic system 17,45 .…”

Section: Discussionmentioning

confidence: 99%

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Cholinergic basal forebrain atrophy in Parkinson's disease with freezing of gait

Gan

Cao

Wang

et al. 2023

Ann Clin Transl Neurol

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Background: Mounting research support that cholinergic dysfunction plays a prominent role in freezing of gait (FOG), which commonly occurs in Parkinson's disease (PD). Basal forebrain (BF), especially the cholinergic nuclei 4 (Ch4), provides the primary source of the brain cholinergic input. However, whether the degeneration of BF and its innervated cortex contribute to the pathogenesis of FOG is unknown. Objective: To explore the role of structural alterations of BF and its innervated cortical brain regions in the pathogenesis of PD patients with freezing. Methods: Magnetic resonance imaging assessments and neurological assessments were performed on 20 PD patients with FOG (PD-FOG), 20 without FOG (PD-NFOG), and 21 healthy participants. Subregion volumes of the BF were compared among groups. Local gyrification index (LGI) was computed to reveal the cortical alternations. Relationships among subregional BF volumes, LGI, and the severity of FOG were evaluated by multiple linear regression. Results: Our study discovered that, compared to PD-NFOG, PD-FOG exhibited significant Ch4 atrophy (p = 4.6 9 10 À5 ), accompanied by decreased LGI values in the left entorhinal cortex (p = 3.00 9 10 À5 ) and parahippocampal gyrus (p = 2.90 9 10 À5 ). Based on the regression analysis, Ch4 volume was negatively associated with FOG severity in PD-FOG group (b = À12.224, T = À2.556, p = 0.031). Interpretation: Our results imply that Ch4 degeneration and microstructural disorganization of its innervated cortical brain regions may play important roles in PD-FOG.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Cholinergic basal forebrain atrophy in Parkinson's disease with freezing of gait

Gan

Cao

Wang

et al. 2023

Ann Clin Transl Neurol

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“…In PD, the role of these neuromodulatory systems in the striatum is important to focus on, since they exhibit plasticity processes in the absence of DA, likely to compensate for the dysfunction of the network. 52,[69][70][71][72] However, these compensatory mechanisms also participate in side effects of L-dopa-based treatments, it is thus important to include the other neuromodulators in the equation of the pharmacological treatments proposed to patients. In this context, the management of vitamin A signaling in PD may contribute to refine PD treatment.…”

Section: Discussionmentioning

confidence: 99%

“…This suggested that in the pathological context of PD, defects in vitamin A signaling may participate to the pathophysiology of the disease through an alteration of striatal neuromodulation. In PD, the role of these neuromodulatory systems in the striatum is important to focus on, since they exhibit plasticity processes in the absence of DA, likely to compensate for the dysfunction of the network 52,69–72 . However, these compensatory mechanisms also participate in side effects of L‐dopa‐based treatments, it is thus important to include the other neuromodulators in the equation of the pharmacological treatments proposed to patients.…”

Section: Discussionmentioning

confidence: 99%

Impact of dietary vitamin A on striatal function in adult rats

et al. 2023

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The striatum is a brain structure involved in the control of voluntary movement. Striatum contains high amounts of retinoic acid, the active metabolite of vitamin A, as well as retinoid receptors, RARβ and RXRγ. Previous studies revealed that disruption of retinoid signaling initiated during development is deleterious for striatal physiology and related motor functions. However, the alteration of retinoid signaling, and the importance of vitamin A supply during adulthood on striatal physiology and function has never been established. In the present study, we investigated the impact of vitamin A supply on striatal function. Adult Sprague–Dawley rats were fed with three specific diets, either sub‐deficient, sufficient, or enriched in vitamin A (0.4, 5, and 20 international units [IU] of retinol per g of diet, respectively) for 6 months. We first validated that vitamin A sub‐deficient diet in adult rats constitutes a physiological model of retinoid signaling reduction in the striatum. We then revealed subtle alterations of fine motor skills in sub‐deficient rats using a new behavioral apparatus specifically designed to test forepaw reach‐and‐grasp skills relying on striatal function. Finally, we showed using qPCR analysis and immunofluorescence that the striatal dopaminergic system per se was not affected by vitamin A sub‐deficiency at adult age. Rather, cholinergic synthesis in the striatum and μ‐opioid receptor expression in striosomes sub‐territories were the most affected by vitamin A sub‐deficiency starting at adulthood. Taken together these results revealed that retinoid signaling alteration at adulthood is associated with motor learning deficits together with discrete neurobiological alterations in the striatum.

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“…Cholinergic neurons of the basal forebrain and brainstem, in particular the pedunculopontine and lateral dorsal tegmental nuclei, which provide cholinergic inputs to the thalamus as well as other sub-cortical structures, show signs of significant degeneration, with up to 50% loss of these cells in post-mortem brains of Parkinson's patients (Hirsch et al, 1987). Whereas basal forebrain degeneration has been linked to the cognitive symptoms of PD, disruption of these output populations is hypothesized to contribute specifically to the disruption of gait and balance (Albin et al, 2022). Importantly, ACh release in the striatum, largely stemming from the local population of cholinergic interneurons, has also been linked to the modulation of locomotion via effects on output from medium spiny projection cells (Gritton et al, 2019).…”

Section: Expanding the Palette Of Functions Subject To Cholinergic Mo...mentioning

confidence: 99%

Special issue on cholinergic signalling

Gritton,

Booth,

Howe

2024

Eur J of Neuroscience

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Cholinergic systems, attentional-motor integration, and cognitive control in Parkinson's disease

Cited by 20 publications

References 103 publications

Cholinergic basal forebrain atrophy in Parkinson's disease with freezing of gait

Cholinergic basal forebrain atrophy in Parkinson's disease with freezing of gait

Impact of dietary vitamin A on striatal function in adult rats

Special issue on cholinergic signalling

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