Dopamine Acetylcholine Imbalance in Parkinson's Disease

Spehlmann, Rainer; Stahl, S. M.

doi:10.1016/s0140-6736(76)93095-6

Cited by 57 publications

(13 citation statements)

References 41 publications

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“…The resulting DA deficit triggers its cardinal clinical symptoms including tremor, rigidity, bradykinesia and postural instability (Cutson et al, 1995 ). Further, the absent inhibition of tonically active cholinergic interneurons by DA results in relative hypercholinism (Spehlmann and Stahl, 1976 ; Aosaki et al, 2010 ), which additionally worsens the pathological motor manifestations (Marti et al, 1999 ; Pisani et al, 2003 ; Ding et al, 2006 ). Consequently, disturbances in cholinergic neurotransmission are associated with symptoms of PD (Lester et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Acetylcholine Neurotransmitter Receptor Densities in the Striatum of Hemiparkinsonian Rats Following Botulinum Neurotoxin-A Injection

et al. 2018

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Cholinergic neurotransmission has a pivotal function in the caudate-putamen, and is highly associated with the pathophysiology of Parkinson's disease. Here, we investigated long-term changes in the densities of the muscarinic receptor subtypes M1, M2, M3 (mAchRs) and the nicotinic receptor subtype α4β2 (nAchRs) in the striatum of the 6-OHDA-induced hemiparkinsonian (hemi-PD) rat model using quantitative in vitro receptor autoradiography. Hemi-PD rats exhibited an ipsilateral decrease in striatal mAchR densities between 6 and 16%. Moreover, a massive and constant decrease in striatal nAchR density by 57% was found. A second goal of the study was to disclose receptor-related mechanisms for the positive motor effect of intrastriatally injected Botulinum neurotoxin-A (BoNT-A) in hemi-PD rats in the apomorphine rotation test. Therefore, the effect of intrastriatally injected BoNT-A in control and hemi-PD rats on mAchR and nAchR densities was analyzed and compared to control animals or vehicle-injected hemi-PD rats. BoNT-A administration slightly reduced interhemispheric differences of mAchR and nAchR densities in hemi-PD rats. Importantly, the BoNT-A effect on striatal nAchRs significantly correlated with behavioral testing after apomorphine application. This study gives novel insights of 6-OHDA-induced effects on striatal mAchR and nAchR densities, and partly explains the therapeutic effect of BoNT-A in hemi-PD rats on a cellular level.

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Section: Introductionmentioning

confidence: 99%

Acetylcholine Neurotransmitter Receptor Densities in the Striatum of Hemiparkinsonian Rats Following Botulinum Neurotoxin-A Injection

et al. 2018

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“…While the majority of cortical neurons are excitatory glutamatergic cells, the remaining 20% of the neuronal population are inhibitory GABA-ergic (gamma-aminobutyric acid) interneurons [3], [4]. An imbalance of excitatory or inhibitory neurotransmitter levels is thought to underlie several developmental and clinical disorders such as attention deficit hyperactivity disorder (ADHD), Parkinson’s disease, schizophrenia and epilepsy [5], [6], [7], [8]. Neurotransmitter activity is also thought to be related to the hemodynamic changes associated with brain activation, but the precise relationship between neurotransmitter levels and cerebral blood flow (CBF) has not yet been established.…”

Section: Introductionmentioning

confidence: 99%

Frontal GABA Levels Change during Working Memory

et al. 2012

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Functional neuroimaging metrics are thought to reflect changes in neurotransmitter flux, but changes in neurotransmitter levels have not been demonstrated in humans during a cognitive task, and the relationship between neurotransmitter dynamics and hemodynamic activity during cognition has not yet been established. We evaluate the concentration of the major inhibitory (GABA) and excitatory (glutamate + glutamine: Glx) neurotransmitters and the cerebral perfusion at rest and during a prolonged delayed match-to-sample working memory task. Resting GABA levels in the dorsolateral prefrontal cortex correlated positively with the resting perfusion and inversely with the change in perfusion during the task. Further, only GABA increased significantly during the first working memory run and then decreased continuously across subsequent task runs. The decrease of GABA over time was paralleled by a trend towards decreased reaction times and higher task accuracy. These results demonstrate a link between neurotransmitter dynamics and hemodynamic activity during working memory, indicating that functional neuroimaging metrics depend on the balance of excitation and inhibition required for cognitive processing.

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“…The dramatic effect of atropine provides indirect evidence of a change of neurotransmitter. Thus cholinergic neurones may be replacing the functions of degenerating dopaminergic neurones quite effectively (Spehlman and Stahl, 1976). Overcompensation may be deleterious and produce dysphagia, as this symptom was associated with the highest incidence of disruption in peristalsis after atropine.…”

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confidence: 99%