Different effects of intranigral and intrastriatal administration of the proteasome inhibitor lactacystin on typical neurochemical and histological markers of Parkinson's disease in rats

Original article Nigrostriatal pathway degeneration in rats after intraperitoneal administration of proteasome inhibitor MG-132

“…A unilateral, intranigral injection of lactacystin at doses of 0.5, 1, 2.5, and 5 µg/2 µl produced after 7 days, distinct decreases in the concentrations of dopamine (DA) and its metabolites (DOPAC, 3-MT, HVA) in the ipsilateral striatum. Such alterations were not observed in the striatal DA content and catabolism either 7, 14, or 21 days after a unilateral, intrastriatal high-dose lactacystin injection (5 and 10 µg/2 µl) [25].…”

“…Among them, degenerative models with MPTP and rotenone are the most commonly used. However, recently it has been postulated that direct administration into elements of the nigrostriatal system [14,25,45] or systemic administration of proteasome inhibitors may serve as a new animal model of PD. The basis of this theory was the results of animal studies indicating that systemically administered (intraperitoneally) proteasome inhibitors like PSI and epoxomicin may, after absorption into the bloodstream, penetrate the intact blood-brain barrier and cause lesions at the substantia nigra, locus coeruleus, and the Meynert nucleus, and in consequence, lead to an impairment of the motor function [32,33,38].…”

Comparison of the Efficacy of Different Drugs on Non-Motor Symptoms of Parkinson’s Disease: a Network Meta-Analysis

“…For example, it can stimulate neurotransmitters or neuromodulators in the brain to act on the Jun protein of the postsynaptic membrane, improve the transcription efficiency of downstream genes by activating the expression of AP-1 and CRE promoting factors, and directly assess the degree of the damage to neurons [54]. Lastly, the increase of Fos protein expression is an important manifestation of neuronal vitality, which can inhibit the increase of tumor necrosis factor, glial-derived neurotrophic factor and cyclinB2 mRNA, further inhibiting striatal neurodegeneration and improving resistance to infection and neurotrophic activity [55, 56]. However, apomorphine will easily degrade under light, and it can inhibit the central nervous system, which causes persistent vomiting, shortness of breath, respiratory depression, acute circulatory failure, coma, death and eosinophilia.…”

Reduced level of synapsin I protein in the rat striatum after intraventricular administration of proteasome inhibitors: preliminary studies

“…Because dopaminergic neurons are especially fragile to this depletion, and substantial loss of dopaminergic terminals in the striatum after proteasome inhibitors administration has been reported [15,28], we assume that observed synapsin I level decrease may reflect changes in population of striatal neurons and/or nigrostriatal terminals. We realise that explanation of cellular mechanisms standing behind our findings needs more intensive studies, but we hope that presented data may be a valuable contribution to the discussion on the mechanisms linking UPS inhibition and survival of neurons.…”