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

% Computing STN lateral connection weight matrix

%% CODE
%----------------STN_lateral connections-----------%
smax = 1.3;  %Strength of lateral connections in stn 2.4-dt0.05 1.3-dt0.1
rs = 1.4; %Radius of lateral connections in stn
nlatstn = 11; % number of laterals in stn
% DA=1;
% ssmax = (smax*(1+0.01*DA))/(1+4*DA); % Bursting to single spike syn
% ssmax = (smax.*(1+0.01.*DA))./(1+4.*DA); % Single spike syn to no syn
% ssmax = (smax*(1+20.5*DA))/(1+30*DA);
% ssmax = RescaleRange(DA,0,1,smax,0.01); %5-3-18
ssmax = smax.*exp(-4.87.*DA); % expontential one (27-8-18)BEST WORKED ONE %15-dt0.05 %4.87-dt0.1
% SS 2.4-->0.01 DA 0-->1

wlatstn = calclatwts(nlatstn,ssmax, rs);

end

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