About the benefits of alpha-synuclein
The "Parkinson's disease substance" is necessary for the development of the neurons it affects
Researchers from the Institute of Physiologically Active Substances of the Russian Academy of Sciences (Chernogolovka, Moscow Region), the Pirogov Russian National Research Institute and the Research Institute of General Pathology and Pathophysiology have clarified how the "shutdown" of alpha-synuclein production, a protein that forms plaques in nerve cells in Parkinson's disease, affects the formation of dopaminergic neurons in embryos (releasing the neurotransmitter dopamine). It turned out that the absence of alpha-synuclein practically does not affect the number of cells in the ventral region of the tire involved in the mechanisms of pleasure and reinforcement. However, the lack of the same protein in the neighboring region of the midbrain, the substantia nigra, significantly changes the rate of appearance of dopaminergic neurons in it. The scientific article was published in the journal PeerJ.
Alpha-synuclein is the main component of Levi's bodies, pathological clusters of protein molecules that form in nerve cells in Parkinson's disease and some dementias. In Parkinsonism, dopamine-releasing neurons of the midbrain containing an excess of Levi's bodies die. Because of this, there are tremors in the limbs and problems with starting and stopping movements. However, alpha-synuclein is also present in healthy dopaminergic neurons in the area of their contacts with other cells. Moreover, previous studies have shown that inactivation (knockout) of the gene encoding alpha-synuclein in mouse embryos leads to the fact that significantly fewer dopaminergic neurons are formed in the midbrain of mice than normal.
Not all nerve cells of the midbrain that secrete dopamine perform the same functions. Those contained in the black substance control movements – namely, they are primarily affected by Parkinsonism. And dopaminergic neurons in the ventral region of the tire are part of a system of connections responsible for pleasure and other positive emotions. With Parkinson's disease, they are among the last to die. This fact prompted Russian researchers to think that the effect of alpha-synuclein on the black substance and the ventral region of the tire during embryonic development may differ.
To test this, they used mice in which the alpha-synuclein gene was inactivated. The brain of the embryos of such mice was extracted on 10.5−13.5 days of pregnancy, then a series of very thin slices were made at the level of the substantia nigra and ventral region of the tire, they were placed in a supportive fluid and antibodies to an enzyme involved in the production of dopamine were added to it. This enzyme is present only in dopaminergic neurons, so antibodies capable of detecting it stained only such cells, but did not affect neurons that secrete glutamate, serotonin or other signaling substances.
Thus, it was possible to find out how the number of dopaminergic neurons in the substantia nigra and ventral region of the mouse tire changes from 10.5 to 13.5 days of embryo existence. It is at this time that the nervous system of rodents goes through critical stages of development. It turned out that the inactivation of the alpha-synuclein gene practically does not affect the appearance of dopamine-releasing cells in the ventral region of the tire. However, "turning off" this gene dramatically changes the rate of formation of the same neurons in the substantia nigra. In the middle of the 11th day, the knocked-out embryos in the substantia nigra of dopaminergic neurons are less than normal. In the next 24 hours, their number increases sharply, "surpassing" the number of similar cells in ordinary embryos, but after that it practically does not increase. By day 13.5, the black substance of the knocked-out embryos contains slightly fewer dopamine-releasing neurons than the same brain region in normal animals.
It turns out that the alpha-synuclein protein is necessary for the timely appearance of dopaminergic neurons of the substantia nigra of the midbrain – the area whose cells suffer most from the accumulation of Levi's bodies in them in Parkinson's disease. However, for some reason, alpha-synuclein does not affect the formation of dopamine-releasing cells in the neighboring area of the midbrain, the ventral region of the tire, involved in other physiological processes than the black substance. The reasons for this difference have yet to be identified.
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