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 [Rvalue,Ravg]=mrcalculate(linear_S,Nneur,Ntime)

%% CREDITS
% Created by
% Vignayanandam R. Muddapu (Ph.D. scholar)
% C/o Prof. V. Srinivasa Chakravarthy
% Indian Institute of Technology Madras
% India

% Computing synchrony

%% CODE
Rvalue=[];phi=[];

phi=3000*ones(Nneur,Ntime-1);
for neur=1:Nneur
        if isempty(linear_S)
            continue
        end
    temptime=linear_S((linear_S(:,2)==neur));
    % temptime =[4    12    21    30    60    78   100   117   126   163   503   652   797   857   940   943];
    j=1;k=1;
    
    while j<numel(temptime)
        %     k=1;
        if temptime(j)==0
            continue
        end
        for i=temptime(j):1:temptime(j+1)-1
            
            phi(neur,i)=(2*pi*(i-temptime(j)))/(temptime(j+1)-temptime(j));
            %                 k=k+1;
        end
        j=j+1;
    end
    
end
phi;
neur;
a=sqrt(-1);
tempM=sum(phi)/numel(phi);
M=exp(a*tempM);
Rvalue=((sum(exp(a*phi))/neur))./M;
Ravg=sum(abs(Rvalue))/numel(Rvalue);


end

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