DREADD Activation of Pedunculopontine Cholinergic Neurons Reverses Motor Deficits and Restores Striatal Dopamine Signaling in Parkinsonian Rats

AbstractThe brainstem-based pedunculopontine nucleus (PPN) traditionally associates with motor function, but undergoes extensive degeneration during Parkinson ’s disease (PD), which correlates with axial motor deficits. PPN-deep brain stimulation (DBS) can alleviate certain symptoms, but its mechanism(s) of action remains unknown. We previously characterized rats hemi-intranigrally injected with the proteasomal inhibitor lactacystin, as an accurate prec linical model of PD. Here we used a combination of chemogenetics with positron emission tomography imaging forin vivo interrogation of discrete neural networks in this rat model of PD. Stimulation of excitatory designer receptors exclusively activated by designer drugs expressed within PPN cholinergic neurons activated residual nigrostriatal dopaminergic neurons to produce profound motor recovery, which correlated with striatal dopamine efflux as well as restored dopamine receptor 1- and dopamine receptor 2-based medium spiny neuron activity, as was ascertained with c-Fos-based immunohistochemistry and stereological cell counts. By revealing that the improved axial-related motor functions seen in PD patients receiving PPN-DBS may be due to stimulation of remaining PPN cholinergic neurons interacting with dopaminergic ones in both the substantia nigra pars compacta and the striatum, our data strongly favor the PPN cholinergic –midbrain dopaminergic connectome as mechanism for PPN-DBS’s therapeutic effects. The...
Source: Neurotherapeutics - Category: Neurology Source Type: research

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ConclusionThe present study confirmed that GPi-DBS is an effective treatment in patients with advanced PD, owing to metabolic changes in the areas involved in motor execution. The absence of relative metabolic decrease in the limbic circuit and the few changes affecting the associative circuit could explain why GPi-DBS is cognitively safe.
Source: Journal of Neurology - Category: Neurology Source Type: research
CONCLUSIONS: MRgFUS thalamotomy is a cost-effective treatment for patients with TDPD, particularly over continued medical therapy. While MRgFUS remains competitive with DBS, the cost-effectiveness advantage is less substantial. These results will help inform the integration of this technology in the healthcare system. PMID: 32764177 [PubMed - as supplied by publisher]
Source: Journal of Neurosurgery - Category: Neurosurgery Authors: Tags: J Neurosurg Source Type: research
Conclusion: The MicrotableTM platform is capable of submillimetric accuracy in patients undergoing stereotactic surgery. It has achieved clinical efficacy in our patients without surgical complications and has demonstrated the potential for superior accuracy compared to both traditional stereotactic frames and other common frameless systems.Stereotact Funct Neurosurg
Source: Stereotactic and Functional Neurosurgery - Category: Neurosurgery Source Type: research
341Background: With the advance of subthalamic nucleus (STN) deep brain stimulation (DBS) in the treatment of Parkinson’s disease (PD), it is desired to identify objective criteria for the monitoring of the therapy outcome. This paper explores the feasibility of metabolic network derived from positron emission tomography (PET) with 18F-fluorodeoxyglucose in monitoring the STN DBS treatment for PD. Methods: Two cohorts with PET imaging were recruited for this study. The cohort I, including 33 PD patients and 33 healthy controls (HCs), were used for the establishment of the PD-related metabolic network pattern (PDRP). ...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Neurodegenerative Diseases Source Type: research
BackgroundDeep brain stimulation (DBS) is a well ‐accepted treatment of Parkinson's disease (PD). Motor phenotypes include tremor‐dominant (TD), akinesia‐rigidity (AR), and postural instability gait disorder (PIGD). The mechanism of action in how DBS modulates motor symptom relief remains unknown.ObjectiveBlood oxygen level ‐dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to determine whether the functional activity varies in response to DBS depending on PD phenotypes.Materials and MethodsSubjects underwent an fMRI scan with DBS cycling ON and OFF. The effects of DBS cycling on BOLD activatio...
Source: Neuromodulation: Technology at the Neural Interface - Category: Biotechnology Authors: Tags: Clinical Research Source Type: research
Abstract The goal of this study was to characterize the spectral characteristics and spatial topography of local field potential (LFP) activity in the internal segment of the globus pallidus (GPi) in patients with Parkinson's disease utilizing directional (segmented) deep brain stimulation (dDBS) leads. Data were collected from externalized dDBS leads of three patients with idiopathic Parkinson's disease after overnight withdrawal of parkinsonian medication at rest and during a cued reach-to-target task. Oscillatory activity across lead contacts/segments was examined in the context of lead locations and contact or...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research
Medtronic obtained the European CE Mark for its Percept PC neurostimulator that uses smart feedback technology to deliver deep brain stimulation to treat Parkinson’s and other neurologic diseases. The so-called BrainSense technology powe...
Source: Medgadget - Category: Medical Devices Authors: Tags: Neurology Neurosurgery Source Type: blogs
AbstractNeuroimaging has seen a paradigm shift away from a formal description of local activity patterns towards studying distributed brain networks. The recently defined framework of the ‘human connectome’ enables global analysis of parts of the brain and their interconnections. Deep brain stimulation (DBS) is an invasive therapy for patients with severe movement disorders aiming to retune abnormal brain network activity by local high frequency stimulation of the basal ganglia. Beyond clinical utility, DBS represents a powerful research platform to study functional connectomics and the modulation of distribute...
Source: Brain - Category: Neurology Source Type: research
Conclusions The treatment used for PD, particularly DA, is associated with the development of ICDs and related behaviors. Susceptibility to these disorders depends on the associated risk factors. ICDs can have serious personal, family, psychosocial, financial, and medical consequences. However, in contrast, artistic activities have been described in patients with PD while undergoing treatment with DA. These patients are compulsive but report a positive influence on quality of life. These findings highlight the need for a very critical approach at the moment of Dopaminergic Replacement therapy choice. Author Contributio...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
CONCLUSION: Our findings provide, for the first time, direct visualization of the PPN using the MP2RAGE sequence on a 7.0T ultrahigh-field MRI, which may improve the accuracy of stereotactic targeting of the PPN and improve the outcomes in patients undergoing DBS.
Source: Clinics - Category: General Medicine Source Type: research
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