The Neuroprotective Effect of N -Docosahexaenoyldopamine on Degenerating Dopaminergic Neurons of the Mesencephalon
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The Neuroprotective Effect of N-Docosahexaenoyldopamine on Degenerating Dopaminergic Neurons of the Mesencephalon S. A. Surkova, *, E. R. Mingazova, V. E. Blokhina, A. I. Sturovaa, N. M. Gretskayab, G. N. Zinchenkob, V. V. Bezuglovb, and M. V. Ugrumova aKoltzov
Institute of Developmental Biology, Russian Academy of Sciences, Moscow, 119334 Russia Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997 Russia *e-mail: [email protected]
b
Received December 3, 2018; revised June 17, 2019; accepted October 17, 2019
Abstract—This study was aimed at evaluating the neuroprotective effect of N-docosahexaenoyldopamine (DHA-DA), an endogenous bioactive lipid of the neurolipin family, on mesencephalic dopaminergic neurons of mouse fetuses in a cell culture under exposure to 1-methyl-4-phenylpyridinium+ (MPP+), a specific neurotoxin for catecholaminergic neurons. The state of neurons in the experiment (MPP+) and in the control (0.9% NaCl) was estimated according to three parameters: the number of surviving dopaminergic neurons, the length of the neurites, and the total content of dopamine in the neurons. DHA-DA was shown to have a dose-dependent neuroprotective effect on degenerating dopaminergic neurons under the influence of MPP+. DHA-DA at concentrations of 0.5 μM or lower does not have a neuroprotective effect. However, at higher concentrations it has a neuroprotective effect, preventing the death of dopaminergic neurons and the degradation of neuritis. At a concentration of 1 μM, DHA-DA protects the neuron cell bodies from degradation to a higher extent than their processes, whereas at a concentration 2 μM it protects and/or stimulates to a greater extent the growth of processes of the surviving neurons. In addition, DHA-DA reduces significantly the loss of dopamine in neurons under exposure to MPP+. Thus, it is shown that DHA-DA has a dose-dependent neuroprotective effect on degenerating dopaminergic neurons. DOI: 10.1134/S1062359020050106
INTRODUCTION Study of the degeneration of nigrostriatal dopaminergic neurons (DAergic neurons) and its prevention with the use of drugs is of great importance for comprehensive understanding of the pathogenesis of Parkinson’s disease (PD) and the development of neuroprotective therapy. Indeed, PD is a neurodegenerative disease characterized by progressive death of DAergic neurons of the brain nigrostriatal system, the key component in motor function regulation. A decrease in the dopamine content in the striatum of patients to a threshold level (20–30% of the norm) leads to disturbances in motor functions, which manifest themselves in the form of tremors, bradykinesia, and rigidity (Agid, 1991). The conventional treatment of patients with the use of dopamine (DA) agonists promotes temporary compensation of the functional failure of nigrostriatal DAergic neurons (Fahn, 2008), but does not prevent the death of these neurons. The lack of effective neuroprotective therapy makes it particularly relevant to search for new drugs with neuro
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