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Excitotoxic loss of dopaminergic cells in PD (Muddapu et al 2019)
 
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Model Information
Model File
Citations
Accession:
244384
"... A couple of the proposed mechanisms, however, show potential for the development of a novel line of PD (Parkinson's disease) therapeutics. One of these mechanisms is the peculiar metabolic vulnerability of SNc (Substantia Nigra pars compacta) cells compared to other dopaminergic clusters; the other is the SubThalamic Nucleus (STN)-induced excitotoxicity in SNc. To investigate the latter hypothesis computationally, we developed a spiking neuron network-model of SNc-STN-GPe system. In the model, prolonged stimulation of SNc cells by an overactive STN leads to an increase in ‘stress’ variable; when the stress in a SNc neuron exceeds a stress threshold, the neuron dies. The model shows that the interaction between SNc and STN involves a positive-feedback due to which, an initial loss of SNc cells that crosses a threshold causes a runaway-effect, leading to an inexorable loss of SNc cells, strongly resembling the process of neurodegeneration. The model further suggests a link between the two aforementioned mechanisms of SNc cell loss. Our simulation results show that the excitotoxic cause of SNc cell loss might initiate by weak-excitotoxicity mediated by energy deficit, followed by strong-excitotoxicity, mediated by a disinhibited STN. A variety of conventional therapies were simulated to test their efficacy in slowing down SNc cell loss. Among them, glutamate inhibition, dopamine restoration, subthalamotomy and deep brain stimulation showed superior neuroprotective-effects in the proposed model."
Reference:
1 .
Muddapu VR, Mandali A, Chakravarthy VS, Ramaswamy S (2019) A Computational Model of Loss of Dopaminergic Cells in Parkinson's Disease Due to Glutamate-Induced Excitotoxicity.
Front Neural Circuits
13
:11
[
PubMed
]
Model Information
(Click on a link to find other models with that property)
Model Type:
Realistic Network;
Brain Region(s)/Organism:
Basal ganglia;
Subthalamic Nucleus;
Cell Type(s):
Abstract Izhikevich neuron;
Channel(s):
Gap Junctions:
Receptor(s):
AMPA;
Gaba;
NMDA;
Gene(s):
Transmitter(s):
Dopamine;
Glutamate;
Gaba;
Simulation Environment:
MATLAB;
Model Concept(s):
Deep brain stimulation;
Parkinson's;
Implementer(s):
Muddapu, Vignayanandam R. [vignan.0009 at gmail.com];
Chakravarthy, Srinivasa V. [schakra at iitm.ac.in];
Search NeuronDB
for information about:
AMPA
;
NMDA
;
Gaba
;
Dopamine
;
Gaba
;
Glutamate
;
/
MuddapuEtAl2019
readme.html
calclatwts.m
deci2str.m
mfrwindow.m
mrcalculate.m
mrintercalculate.m
psth.m
PSTH_plotting.m
SEM.m
SEM_GPU.m
SEM_run.m
ST_psth.m
sub_sampling.m
sub_sampling_firings.m
weightcal_gpe.m
weightcal_snc.m
weightcal_stn.m
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