Imperial College London
Alternate

ProfessorDavidDexter

Faculty of Medicine, Department of Brain Sciences

Visiting Professor of Neuropharmacology
 
 
 
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Contact

 

+44 (0)20 7594 6665d.dexter Website

 
 
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Location

 

E411Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sharma:2020:10.1007/s13311-019-00830-4,
author = {Sharma, PK and Wells, L and Rizzo, G and Elson, JL and Passchier, J and Rabiner, EA and Gunn, RN and Dexter, DT and Pienaar, IS},
doi = {10.1007/s13311-019-00830-4},
journal = {Neurotherapeutics},
pages = {1120--1141},
title = {DREADD activation of pedunculopontine cholinergic neurons reverses motor deficits and restores striatal dopamine signaling in parkinsonian rats.},
url = {http://dx.doi.org/10.1007/s13311-019-00830-4},
volume = {17},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The 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 preclinical model of PD. Here we used a combination of chemogenetics with positron emission tomography imaging for in 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. These findings have implications for refining PPN-DBS as a promising treatment modality available to PD patients.
AU  - Sharma,PK
AU  - Wells,L
AU  - Rizzo,G
AU  - Elson,JL
AU  - Passchier,J
AU  - Rabiner,EA
AU  - Gunn,RN
AU  - Dexter,DT
AU  - Pienaar,IS
DO  - 10.1007/s13311-019-00830-4
EP  - 1141
PY  - 2020///
SN  - 1878-7479
SP  - 1120
TI  - DREADD activation of pedunculopontine cholinergic neurons reverses motor deficits and restores striatal dopamine signaling in parkinsonian rats.
T2  - Neurotherapeutics
UR  - http://dx.doi.org/10.1007/s13311-019-00830-4
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31965550
UR  - https://link.springer.com/article/10.1007%2Fs13311-019-00830-4
UR  - http://hdl.handle.net/10044/1/77258
VL  - 17
ER  -
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