Related Experiment Video
Updated: Jun 7, 2025
11:12
Controlling Parkinson's Disease With Adaptive Deep Brain Stimulation
Published on: July 16, 2014
22.4K
Modulating the cholinergic system-Novel targets for deep brain stimulation in Parkinson's disease
V Witzig1, R Pjontek2,3, S K H Tan4,5
1Department of Neurology, RWTH Aachen University, Aachen, Germany.
Journal of Neurochemistry
|November 18, 2024
Summary
Parkinson's disease (PD) involves more than just motor symptoms. Targeting the cholinergic system via deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) and nucleus basalis of Meynert (NBM) may help treat non-motor symptoms.
Area of Science:
- Neuroscience
- Neurology
- Movement Disorders
Background:
- Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms like rigidity and tremor, stemming from nigrostriatal pathway degeneration.
- PD is a multi-system disease; non-motor symptoms such as postural instability, gait freezing, falls, and cognitive decline result from dysfunction in neurotransmitter systems beyond the dopaminergic axis.
- Current treatments like levodopa and subthalamic nucleus/globus pallidus internus deep brain stimulation (DBS) primarily target motor symptoms, often failing to alleviate axial and cognitive impairments.
Purpose of the Study:
- To review the critical role of the cholinergic system in PD pathophysiology.
- To explore the potential of deep brain stimulation (DBS) targeting cholinergic structures, specifically the pedunculopontine nucleus (PPN) and nucleus basalis of Meynert (NBM), for managing PD symptoms.
- To provide insights into patient selection, surgical techniques, and stimulation parameters for PPN and NBM DBS in PD.
Main Methods:
- Comprehensive literature review focusing on cholinergic dysfunction in Parkinson's disease.
- Analysis of existing research on the efficacy of deep brain stimulation (DBS) targeting the pedunculopontine nucleus (PPN) and nucleus basalis of Meynert (NBM).
- Discussion of clinical evidence and proposed mechanisms for PPN and NBM DBS in treating non-motor and axial symptoms of PD.
Main Results:
- Cholinergic system alterations significantly contribute to axial symptoms and cognitive deficits in Parkinson's disease.
- Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) and nucleus basalis of Meynert (NBM) shows promise in ameliorating symptoms resistant to conventional dopaminergic therapies.
- Evidence suggests that targeting these cholinergic centers can improve gait, balance, and cognitive function in PD patients.
Conclusions:
- Cholinergic pathways are vital for functions affected in advanced Parkinson's disease.
- Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) and nucleus basalis of Meynert (NBM) represents a promising therapeutic strategy for refractory axial and cognitive symptoms in PD.
- Further research and refined clinical protocols are needed to optimize patient selection and stimulation paradigms for cholinergic DBS in Parkinson's disease.
Keywords:
Parkinson's diseaseacetylcholinedeep brain stimulationneuromodulationnucleus basalis of Meynertpedunculopontine nucleusMore Related Videos
07:14A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test
Published on: May 31, 2016
14.7K
14:14Targeting Neuronal Fiber Tracts for Deep Brain Stimulation Therapy Using Interactive, Patient-Specific Models
Published on: August 12, 2018
8.8K
Related Concept Videos
01:24Parkinson's Disease: Treatment
222
Neurodegenerative disorders, such as Parkinson's Disease (PD), involve the gradual and irreversible destruction of neurons in particular brain areas. These disorders exhibit standard features like proteinopathies, selective vulnerability of some neurons, and an interaction of intrinsic properties, genetics, and environmental influences in neural injury.
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of...
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of...
222
00:59Direct-Acting Cholinergic Agonists: Pharmacological Actions
1.2K
Direct-acting cholinergic agonists exert their pharmacological actions by mimicking the effects of acetylcholine on postsynaptic muscarinic receptors to generate parasympathetic responses. These agents elicit a range of physiological responses, including cardiovascular effects. For example, activation of muscarinic receptors induces bradycardia, decreased cardiac output, reduced peripheral resistance, and consequent hypotension. In the eye, stimulation of M3 receptors leads to smooth muscle...
1.2K
01:30Indirect-Acting Cholinergic Agonists: Pharmacological Actions
618
Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
618
01:15Parkinson's Disease: Overview
482
Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is...
482
01:31Direct-Acting Cholinergic Agonists: Pharmacokinetics
1.1K
Direct-acting cholinergic agonists, such as synthetic choline esters and naturally occurring alkaloids, exert their effects by enhancing the actions of acetylcholine and stimulating the parasympathetic nervous system. Synthetic choline esters share structural similarities with acetylcholine. For example, they have a positively charged quaternary ammonium or onium group, contributing to their hydrophilic characteristics. As a result, they are poorly absorbed in the body through oral...
1.1K
01:11Direct-Acting Cholinergic Agonists: Therapeutic Uses
693
Direct-acting cholinergic agonists have many therapeutic uses in various medical fields. Choline esters, including acetylcholine, have limited clinical utility due to their non-selectivity and short duration of action. Still, acetylcholine and carbachol are applied topically during ophthalmologic surgery to induce miosis. Pilocarpine, a muscarinic and ganglionic stimulator, effectively treats open-angle glaucoma and alleviates xerostomia and dry mouth caused by radiotherapy or Sjögren...
693