The Moscow researchers from the Institute of Higher Nervous Activity and Neurophysiology Russian (Academy of Sciences) in the survey composed by them reviewed several types of the most common experimental models of Parkinson’s disease as applied to animals. As a result of this effort, it has turned out that none of the models described by them is able to fully and adequately imitate all clinical, pathophysiological, morphological, biochemical and other aspects of the disease behavior.
Parkinson’s disease is a chronical neurodegenerative disease with selective injuries of brain neurons and, as a result, abnormalities of the organism’s movement, emotional and cognitive activity. The disease usually develops slowly and declares itself clinically after the age of 50, when a substantial amount of neurons – about 60% to 80% - have been already injured.
Till recently, it has been considered that Parkinson’s disease is provoked exclusively by environmental factors. However, after family or heritable forms of the disease have been discovered, the researchers began an active search for and intense investigations of underlying genes and proteins coded by these genes. Although Parkinson’s disease is caused by toxins in 95% of cases, investigation of involved genes helps to understand the origin and evolution of not only heritable but also sporadical (unheritable) forms of the disease, as in both cases the same genes and respective proteins are involved.
The most common experimental models of Parkinspn’s disease on animals are built based on these two factors – genetic and toxic (environmental) factor.
Genetic models are based on “switching off” or changing the genes, which control specific proteins synthesis. The authors’ research considered three of such models. With the alpha-synucleic mice, the alfa-synucleic gene – the first identified gene connected with Parkinson’s disease – is either absent at all or vice versa is over-expressed. The gene (the mutation of which accumulates a large amount of proteins in the cells, which cause damaging poisonous action) was respectively “switched off” with Parkin knockout mice. As for the DJ-1 knockout mice, as it is evident from the name, the DJ-1 gene was “switched off”, this gene being connected with early, beginning of the disease (before 40 years).
Toxic models are based on damaging effects of chemical substances that act via oxidizing evolution and free radical accumulation in the cell. In their research, the authors also considered the most popular toxic models. The first model – hemi-parkinsonism model – is characterized by introduction of the 6-OHDA toxin directly into the brain cells. Upon one-way introduction of this toxin, neuron death occurs already in a day after introduction and reaches its maximum within 72 hours.
The ÌÐÒÐ toxin influence – the basis of the second toxic model investigated by the authors – was discovered by accident. Early in the 80s, some drug addicts who used to take a self-made narcotic– medyperidine – began to show symptoms of akinesia– total absence of voluntary movements, which is also one of the symptoms of Parkinson’s disease. It became clear later that the reason for akinesia was the ÌÐÒÐ substance – a mistakenly synthesized substance but very close in structure to narcotic.
Under the third considered model, introduction of the rotenone toxin to rats also caused the death of neurons, decrease of motion activity, formation of a compressed posture, and in some cases to rigidity (numbness) and catalepsy (pathologically prolonged preservation of a formed posture).
Having thoroughly investigated six most common models of two types, the researchers came to the conclusion that none of the currently used experimental models of Parkinson’s disease was able to fully imitate the entire picture of clinical course. As a rule, only individual elements of the disease are reproduced in some way, but the entire picture remains undisclosed.