MorphologyMorphology1026-35432949-2556Eco-Vector8990410.17816/morph.89904Research ArticleThe use of L-dopa induces the resistance of Mauthner neurons to the neurotoxic action of beta-amyloidTirasNadezhda R.<p>Dr. Sci. (Biol.), Leading Research Associate</p>ntiras@rambler.ruhttps://orcid.org/0000-0003-2624-8816MikheevaIrina B.<p>Cand. Sci. (Biol.), Senior Research Associate</p>mikheirina@yandex.ruhttps://orcid.org/0000-0001-8054-0477MikhailovaGulnara Z.<p>Cand. Sci. (Biol.), Senior Research Associate</p>mihailova_g@rambler.ruhttps://orcid.org/0000-0002-9785-4584PenkovaNadezhda A.<p>Cand. Sci. (Biol.), Research Associate</p>kokanchik@rambler.ruhttps://orcid.org/0000-0002-5903-5908KhutsyanSergey S.khutzian@yandex.ruhttps://orcid.org/0000-0002-9572-3361Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences11022023160111190912202107102022Copyright © 2023, Eco-Vector2023<p><strong><em>BACKGROUND: </em></strong>Mauthner goldfish (<em>Carassius auratus</em> (L)) cells serve as model objects for studying brain pathologies at the level of identified neurons and their individual dendrites. L-dopa may be an agent that decelerates the destruction of neurons caused by the toxic effects of beta-amyloid.</p>
<p><strong><em>AIMS:</em></strong> To study the three-dimensional structure of Mauthner neurons in goldfish and the ultrastructure of their afferent synapses under the influence of L-dopa and the toxic 2535 fragment of beta-amyloid.</p>
<p><strong><em>MATERIAL AND METHODS:</em></strong> This study was performed on the Mauthner neurons of goldfish fry (<em>n</em>=12) by using light and electron microscopy. Serial sections 3 m thick were used to identify and integrally reconstruct the structure of Mauthner neurons; determine the volume of the soma and ventral and lateral dendrites; and study the structure of afferent synapses.</p>
<p><strong><em>RESULTS:</em></strong> The use of L-dopa stabilized the size of the soma and ventral dendrites. The reduction in the volume of lateral dendrites was accompanied either by an increase in the volume of their branches under the action of beta-amyloid followed by that of L-dopa or by an increase in the volume of medial dendrites under the action of L-dopa followed by that of beta-amyloid. Although pathological changes in the ultrastructure of neurons and afferent synapses were not found, signs of early amyloidosis were detected.</p>
<p><strong><em>CONCLUSION:</em></strong> The use of L-dopa decelerates the degeneration of Mauthner neurons. The resistance of whole neurons to the neurotoxic action of beta-amyloid has been suggested to be due to the mechanism of structural homeostasis aiming at the compensatory restoration of the morphological organization of neurons.</p>Mauthner neuronssynapsesL-dopabeta-amyloidмаутнеровские нейронысинапсыL-дофабета-амилоид[Vickers JC, Mitew S, Woodhouse A, et al. Defining the earliest pathological changes of Alzheimer’s disease. Curr Alzheimer Res. 2016;13(3):281–287. doi: 10.2174/1567205013666151218150322][Tanvir Z, Rivera D, Severi KE, et al. Evolutionary and homeostatic changes in morphology of visual dendrites of Mauthner cells in Astyanax blind cavefish. J Comp Neurol. 2021;529(8):1779–1786. doi: 10.1002/cne.25056][Tiras NR, Mikheeva IB, Mikhailova GZ, et al. Compensatory changes in Mauthner neurons in goldfish induced by sensory stimulation and application of β-amyloid. Neurosci Behav Physiol. 2019;49(6):784–790 doi: 10.1007/s11055-019-00802-3][Moreno-Castilla P, Rodrigues-Duran LF, Guzman-Ramos K, et al. Dopaminergic neurotransmission dysfunction induced by amyloid-β transforms cortical long-term potentiation into long-term depression and produces memory impairment. Neurobiol Aging. 2016;41:187–199. doi: 1016/j.neurobiolaging.2016.02.021][Medan V, Preuss T. The Mauthner-cell circuit of fish as a model system for startle plasticity. J Physiol Paris. 2014;108(2–3):129–140. doi: 10.1016/j.jphysparis.2014.07.006][Moshkov DA, Pavlik LL, Shubina VS, et al. Cytoskeletal regulation of the cellular function by dopamine. Biophysics. 2010;55:750–755. doi: 10.1134/s0006350910050118][Tiras NR, Mikheeva IB, Mikhailova NA, et al. Dopamine improves resistance of dendrites of Mauthner neurons to destruction induced by sensory stimulation and application of β-amyloid. Bull Exp Biol Med. 2020;169(2):266–269. doi: 10.1007/s10517-020-04865-y][Ambree O, Richter H, Sachser N, et al. Levodopa ameliorates learning and memory deficits in a murine model of Alzheimer’s disease. Neurobiol Aging. 2009;30(8):1192–1204. doi: 10.1016/j.neurobiolaging.2007.11.010][Li J, Zhu M, Manning-Bog AB, et al. Dopamine and L-dopa disaggregate amyloid fibrils: implications for Parkinson’s and Alzheimer’s disease. FASEB J. 2004;18(9):962–964. doi: 10.1096/fj.03-0770fje][Cochran JN, Hall AM, Roberson ED. The dendritic hypothesis for Alzheimer’s disease pathophysiology. Brain Res Bull. 2014;103:18–28. doi: 10.1016/j.brainresbull.2013.12.004][Mikhailova GZ, Kokanova NA, Tiras NR, Moshkov DA. Trekhmernaya rekonstruktsiya i opredelenie obema neyrona. Moscow: URSS; 2012. 80 p. (In Russ).][Samsonovich AV, Ascoli GA. Morphological homeostasis in cortical dendrites. Proc Natl Acad Sci USA. 2006;103(5):1569–1574. doi: 10.1073/pnas.0510057103]