Levodopa-Induced Toxicity in Parkinson's Disease (Muddapu et al, 2022)

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Accession:263719
"... We present a systems-level computational model of SNc-striatum, which will help us understand the mechanism behind neurodegeneration postulated above and provide insights into developing disease-modifying therapeutics. It was observed that SNc terminals are more vulnerable to energy deficiency than SNc somas. During L-DOPA therapy, it was observed that higher L-DOPA dosage results in increased loss of terminals in SNc. It was also observed that co-administration of L-DOPA and glutathione (antioxidant) evades L-DOPA-induced toxicity in SNc neurons. Our proposed model of the SNc-striatum system is the first of its kind, where SNc neurons were modeled at a biophysical level, and striatal neurons were modeled at a spiking level. We show that our proposed model was able to capture L-DOPA-induced toxicity in SNc, caused by energy deficiency."
Reference:
1 . Muddapu VR, Vijayakumar K, Ramakrishnan K, Chakravarthy VS (2022) A Multi-Scale Computational Model of Levodopa-Induced Toxicity in Parkinson's Disease Front. Neurosci.
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network;
Brain Region(s)/Organism: Basal ganglia; Globus pallidus externa (GPe); Striatum; Subthalamic Nucleus;
Cell Type(s): Substantia nigra pars compacta DA cell; Neostriatum medium spiny direct pathway GABA cell; Globus pallidus principal GABA cell; Abstract Izhikevich neuron; Hodgkin-Huxley neuron; Subthalamus nucleus projection neuron;
Channel(s): Na/K pump; Na/Ca exchanger; Kir; IK Skca; Ca pump; I A; I Ca,p; I h; I K,Ca; I K; I N;
Gap Junctions:
Receptor(s): NMDA; GabaA; AMPA;
Gene(s):
Transmitter(s): Dopamine; Gaba; Glutamate;
Simulation Environment: MATLAB; MATLAB (web link to model);
Model Concept(s): 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:  Neostriatum medium spiny direct pathway GABA cell; Substantia nigra pars compacta DA cell; Globus pallidus principal GABA cell; GabaA; AMPA; NMDA; I N; I A; I K; I h; I K,Ca; Na/Ca exchanger; Na/K pump; I Ca,p; Ca pump; Kir; IK Skca; Dopamine; Gaba; Glutamate; 
function [firings]=ConvertAPtoST(input_firings,Pnrn)
%% CREDITS
% Created by
% Vignayanandam R. Muddapu (Ph.D. scholar)
% C/o Prof. V. Srinivasa Chakravarthy
% Indian Institute of Technology Madras
% India

% Converting Action potential to spike train
% input_firings = times of action action potential above certain threshold
% Pnrn = number of neurons

%% CODE
% Pnrn=16;
firings=[];
for i=1:Pnrn
    inds=input_firings((input_firings(:,2)==i));
    zero=zeros(1000,1);
    inds1=[zero;inds];
    isi=diff(inds1);
    ind=find(isi>10)-999;
    spikes=inds(ind);
    firings=[firings; spikes,i+0*spikes];
end

% [Y,I]=sort(firings(:,1));
% firings=firings(I,:);

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