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

"... 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."

Model Type: Realistic Network

Region(s) or Organism(s): 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

Currents: 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

Receptors: NMDA; GabaA; AMPA

Transmitters: Dopamine; Gaba; Glutamate

Model Concept(s): Parkinson's

Simulation Environment: MATLAB; MATLAB (web link to model)

Implementer(s): Muddapu, Vignayanandam R. [vignan.0009 at gmail.com]; Chakravarthy, Srinivasa V. [schakra at iitm.ac.in]


Muddapu VR, Vijayakumar K, Ramakrishnan K, Chakravarthy VS. (2022). A Multi-Scale Computational Model of Levodopa-Induced Toxicity in Parkinson's Disease Front. Neurosci.