Changes in the Content of Sphingolipids in the Nigrostriatal Dopaminergic System in the Brain of Mice with a Neurotoxic Model of Parkinson’s Diseaseстатья
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Дата последнего поиска статьи во внешних источниках: 15 декабря 2021 г.
Аннотация:It was shown that sphingolipids are necessary for the normal functioning of neurons, and disturbance of their metabolism accompanies the development of brain diseases, including Parkinson's disease (PD). Since the possibilities for studying the role of sphingolipids in the pathogenesis of PD in patients are extremely limited, experimental models must be used to solve this problem. Thus, in this work, using chromatography-mass spectrometry, the content of key molecular species of sphingolipids, total ceramides, hexosylceramides, and their derivatives, sphingosine and sphinganine, with proapoptotic properties in mice were studied using a model of the clinical stage of PD for the first time. This model was obtained by systemically administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which in the brain turns into MPP +, a toxin for catecholaminergic neurons. In the control, instead of MPTP, 0.9% NaCl was injected. It was shown that the total concentration of all studied sphingolipids increases in the substantia nigra, the location of dopaminergic neuron bodies, compared to the control. This occurred due to an increase in the concentration of ceramides associated with fatty acids, such as C18:1/14:0, C18:1/18:0, C18:1/24:1, and monohexosylceramides associated with fatty acids such as C18:1/18:0 and C18:1/24:1. Unlike the substantia nigra, the striatum, the site of projection of dopaminergic axons, had no changes in the content of sphingolipids. These data indicate that the death of nigrostriatal dopaminergic neurons in the PD model is accompanied by a change in the metabolism of sphingolipids, which opens up new possibilities for studying their role in the pathogenesis of this disease and in the search for a new class of drugs that correct sphingolipid metabolism.