ABSTRACT
Parkinson's disease (PD) is one of incurable socially significant diseases. Success in the PD treatment is associated with the development of the technology of preclinical diagnosis and neuroprotective treatment of the disease. In the experimental model of the preclinical PD stage in rats created by intranasal administration of the proteasome inhibitor lactacystin, signs of depression as an anhedonia symptom were detected for the first time. Anhedonia was combined with the death of about one third of dopamine (DA)-ergic neurons in the ventral tegmental area of the midbrain and their axons in the ventral striatum; and a decrease of dopamine concentration in the ventral striatum (by 40%) and the tyrosine hydroxylase level in surviving DA-ergic neurons. The signs of depression may be an early marker of PD, signaling the onset of neurodegeneration in the mesolimbic brain system and increasing functional deficit of the DA-ergic transmission in the ventral striatum. The study results can be applied to the development of the technology of preclinical PD diagnosis and pathogenetic therapy.
Subject(s)
Anhedonia , Parkinson Disease , Ventral Tegmental Area , Animals , Mesencephalon , Parkinson Disease/complications , Parkinson Disease/diagnosis , Rats , Substantia Nigra , Ventral Tegmental Area/pathologyABSTRACT
An experimental model of the preclinical stage of Parkinson's disease was induced by double intranasal administration of the proteasome inhibitor lactacystin. The results demonstrated signs of cognitive impairments expressed as impaired non-associative learning. This was related to degeneration of one-third of dopaminergic neurons in the ventral tegmental area of the midbrain and their axons in the dorsolateral prefrontal cortex. Impairment of non-associative learning may be an early non-motor marker of Parkinson's disease indicating the start of neurodegenerative processes in the dopaminergic mesocortical system of the brain.
