Signs of anhedonia and destructive changes in the ventral tegmental area of the midbrain in the model of the preclinical Parkinson’s disease stage in experiment

Ekimova I.V.; Gazizova A.R.; Karpenko M.N.; Plaksina D.V.

doi:https://doi.org/10.17116/jnevro201811809161

Ekimova I.V.

Sechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of Sciences, St. Petersburg, Russia

Gazizova A.R.

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russia

Karpenko M.N.

FGBU "Nauchno-issledovatel'skiĭ institut ksperimental'noĭ meditsiny" Severo-Zapadnogo otdeleniia RAMN, Sankt-Peterburg;
FGBOU VPO "Sankt-Peterburgskiĭ gosudarstvennyĭ politekhnicheskiĭ universitet"

Plaksina D.V.

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russia

Signs of anhedonia and destructive changes in the ventral tegmental area of the midbrain in the model of the preclinical Parkinson’s disease stage in experiment

Authors:

Ekimova I.V., Gazizova A.R., Karpenko M.N., Plaksina D.V.

More about the authors

Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2018;118(9): 61‑67

DOI: 10.17116/jnevro201811809161

Read: 2683 times

Download PDF (RU)

Contact the author

Table of contents

To cite this article:

Ekimova IV, Gazizova AR, Karpenko MN, Plaksina DV. Signs of anhedonia and destructive changes in the ventral tegmental area of the midbrain in the model of the preclinical Parkinson’s disease stage in experiment. S.S. Korsakov Journal of Neurology and Psychiatry. 2018;118(9):61‑67. (In Russ.)
https://doi.org/10.17116/jnevro201811809161

Подписка 2026 Журнал неврологии и психиатрии им. С.С. Корсакова (S.S. Korsakov Journal of Neurology and Psychiatry)

Использование инфографики авторами научных работ

Close metadata

Abstract:

Parkinson’s disease (PD) is one of incurable socially significant diseases. Success in the PD treatment is associated with the development of the technology of preclinical diagnosis and neuroprotective treatment of the disease. In the experimental model of the preclinical PD stage in rats created by intranasal administration of the proteasome inhibitor lactacystin, signs of depression as an anhedonia symptom were detected for the first time. Anhedonia was combined with the death of about one third of dopamine (DA)-ergic neurons in the ventral tegmental area of the midbrain and their axons in the ventral striatum; and a decrease of dopamine concentration in the ventral striatum (by 40%) and the tyrosine hydroxylase level in surviving DA-ergic neurons. The signs of depression may be an early marker of PD, signaling the onset of neurodegeneration in the mesolimbic brain system and increasing functional deficit of the DA-ergic transmission in the ventral striatum. The study results can be applied to the development of the technology of preclinical PD diagnosis and pathogenetic therapy.

Keywords:

anhedonia

ventral tegmental area of the midbrain

striatum

lactacystin

Parkinson’s disease

Authors:

Ekimova I.V.

Sechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of Sciences, St. Petersburg, Russia

Gazizova A.R.

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russia

Karpenko M.N.

Plaksina D.V.

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russia

Close metadata

References:

Gusev EI, Gekht AB, Popov GR, Volkova NA, Pastukhov YuF, Pronina TS, Chesnokova AYu, Ekimova IV. Bolezn’ Parkinsona. Klinika, diagnostika i lechenie. Neurodegenerative Diseases: Fundamental and Applied Issues. Pod red. Ugryumova M.V. M.: Nauka; 2010. (In Russ.)
Levin OS, Artemyev DV, Bril EV, Kulua TK. Parkinson’s disease: modern approaches to diagnosis and treatment. Prakticheskaya meditsina. 2017;1(102):45-51. (In Russ.)
Assogna F, Cravello L, Caltagirone C, Spalletta G. Anhedonia in Parkinson’s disease: a systematic review of the literature. Movement Disorders. 2011;26(10):1825-1834. https://doi.org/10.1002/mds.23815
Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K. Stages in the development of Parkinson’s disease related pathology. Cell and tissue research. 2004;318:121-134. https://doi.org/10.1007/s00441-004-0956-9
Ugryumov MV. Translyatsionnaya i profilakticheskaya meditsina kak osnova bor’by s bolezn’yu Parkinsona. Bolezn’ Parkinsona i rasstroistva dvizhenii. Rukovodstvo dlya vrachei. Po materialam III Natsional’nogo kongressa po bolezni Parkinsona i rasstroistvom dvizhenii. M. 2014;14-16. (In Russ.)
Pastukhov YuF, Ekimova IV, Chesnokova AV. Molekulyarnye mekhanizmy patogeneza bolezni Parkinsona i perspektivy preventivnoi terapii. Neirodegenerativnye zabolevaniya — ot genoma do tselostnogo organizma. Chast’ I. Motornaya funktsiya i ee regulyatsiya v norme i pri patologii. Pod red. Ugryumova M.V. M.: Nauchnyi mir; 2014. (In Russ.)
Cummings JL. Depression and Parkinson’s disease: a review. The American Journal of Psychiatry. 1992;149(4):443-454. https://doi.org/10.1176/ajp.149.4.443
Levin OS. Diagnostika i lechenie depressii pri bolezni Parkinsona. Aktual’nye Voprosy nevrologii. 2006;2:2-20. (In Russ.)
Fedorova NV, Nikitina AV. Depressiya, apatiya i angedoniya pri bolezni Parkinsona: mekhanizmy razvitiya nemotornykh proyavlenii i podkhody k korrektsii. Nervnye Bolezni. 2012;3:31-36. (In Russ.)
Szatmari S, Illigens BMW, Siepmann T, Pinter A, Takats A, Bereczki D. Neuropsychiatric symptoms in untreated Parkinson’s disease. Neuropsychiatric disease and treatment. 2017;13:815-826. https://doi.org/10.2147/NDT.S130997
Braak H, Braak E. Pathoanatomy of Parkinson’s disease. Journal of Neurology. 2000;247(suppl 2):II3-II10. https://doi.org/10.1007/PL00007758
Uhl GR, Hedreen JC, Price DL. Parkinson’s disease Loss of neurons from the ventral tegmental area contralateral to therapeutic surgical lesions. Neurology. 1985;35(8):1215. https://doi.org/10.1212/WNL.35.8.1215
Shen CC, Tsai SJ, Perng CL, Kuo BI, Yang AC. Risk of Parkinson disease after depression: a nationwide population-based study. Neurology. 2013;81(17):1538-1544. https://doi.org/10.1212/WNL.0b013e3182a956ad
Ebrahimi-Fakhari D, Wahlster L, McLean PJ. Protein degradation pathways in Parkinson’s disease: curse or blessing. Acta Neuropathologica. 2012;124(2):153-172. https://doi.org/10.1007/s00401-012-1004-6
Abdurasulova IN, Ekimova IV, Matsulevich AV, Gazizova AR, Klimenko VM, Pastukhov YuF. Impairment of non-associative learning in a rat experimental model of preclinical stage of Parkinson’s disease. Doklady Biological Sciences. 2017;476(1):188-190. (In Russ.) https://doi.org/10.1134/S0012496617050039
Karpenko MN, Muruzheva ZM, Pestereva NS, Ekimova I.V. Infectious hypothesis of Parkinson disease. Rossiiskii Fiziologicheskii Zhurnal im. I.M. Sechenova. 2017;103(8):841-853. (In Russ.)
Ekimova IV, Simonova VV, Guzeev MA, Lapshina KV, Chernyshev MV, Pastukhov YuF. Changes in sleep characteristics of rat preclinical model of Parkinson’s disease based on attenuation of the ubiquitin-proteasome system activity in the brain. Journal of Evolutionary Biochemistry and Physiology. 2016;52(6):463-474. (In Russ.) https://doi.org/10.1134/S1234567816060057
Pastukhov YuF, Simonova VV, Chernyshev MV, Guzeev MA, Shemyakova TS, Ekimova IV. Signs of sleep and behavioral disturbances indicating the initial stage of neurodegeneration in the model of Parkinson’s disease. Zhurnal Evolyutsionnoi Biokhimii i Fiziologii. 2017;53(5):383-386. (In Russ.)
Plaksina DV, Ekimova IV, Karpenko MN, Pastukhov YuF. Assessment of the functional state of the nigrostriatal system of the brain in experimental model of the preclinical stage of Parkinson’s disease in rats. Zhurnal Evolyutsionnoi Biokhimii i Fiziologii. 2017;53(5):386-388. (In Russ.)
Grønli J, Murison R, Fiske E, Bjorvatn B, Sørensen E, Portas CM, Ursin R. Effects of chronic mild stress on sexual behavior, locomotor activity and consumption of sucrose and saccharine solutions. Physiology & Behavior. 2005;84(4):571-577. https://doi.org/10.1016/j.physbeh.2005.02.007
Pastukhov YuF, Chesnokova AYu, Yakimchuk AA, Ekimova IV, Romanova IV, Khudik KA. Sleep changes during degeneration of neurons in the substantia nigra induced by inhibitor of proteasomes lactacystin in rats. Rossiiskii Fiziologicheskii Zhurnal im. I.M. Sechenova. 2010;96(12):1190-1202. (In Russ.)
Paxinos G, Watson C. The rat brain in stereotaxic coordinates. New York: Academic; 1986.
Merkulov GA. Kurs patogistologicheskoi tekhniki. L.: Meditsina; 1969. (In Russ.)
Nair-Roberts RG, Chatelain-Badie SD, Benson E, White-Cooper H, Bolam JP, Ungless MA. Stereological estimates of dopaminergic, GABAergic and glutamatergic neurons in the ventral tegmental area, substantia nigra and retrorubral field in the rat. Neuroscience. 2008;152:1024-1031. https://doi.org/10.1016/j.neuroscience.2008.01.046
McNaught KS, Belizaire R, Isacson O, Jenner P, Olanow CW. Altered proteasomal function in sporadic Parkinson’s disease. Experimental Neurolology. 2003;179(1):38-46. https://doi.org/10.1006/exnr.2002.8050
Nestler EJ, Carlezon WAJr. The mesolimbic dopamine reward circuit in depression. Biological Psychiatry. 2006;59(12):1151-1159. https://doi.org/10.1016/j.biopsych.2005.09.018
Pagonabarraga J, Kulisevsky J, Strafella AP, Krack P. Apathy in Parkinson’s disease: clinical features, neural substrates, diagnosis, and treatment. Lancet Neurology. 2015;14(5):518-531. https://doi.org/10.1016/S1474-4422(15)00019-8
Kunig G, Leenders KL, Martin-Solch C, Missimer J, Magyar S, Schultz W. Reduced reward processing in the brains of Parkinsonian patients. Neuroreport. 2000;11:3681-3687.
Derkach KV, Romanova IV, Shpakov AO. Functional interaction between the dopamine and melanocortin systems in the brain. Rossiiskii Fiziologicheskii Zhurnal im. I.M. Sechenova. 2016;102(12):1393-1405. (In Russ.)
Lim BK, Huang KW, Grueter BA, Rothwell PE, Malenka RC. Anhedonia requires MC4R-mediated synaptic adaptations in nucleus accumbens. Nature. 2012;487(7406):183-189. https://doi.org/10.1038/nature11160
Pandit R, Omrani A, Luijendijk MC, de Vrind VA, Van Rozen AJ, Ophuis RJ, Garner K, Kallo I, Ghanem A, Liposits Z, Conzelmann KK, Vanderschuren LJ, la Fleur SE, Adan RA. Melanocortin 3 Receptor signaling in midbrain dopamine neurons increases the motivation for food reward. Neuropsychopharmacology. 2016;41(9):2241-2251. https://doi.org/10.1038/npp.2016.19
Pandit R, van der Zwaal EM, Luijendijk MC, Brans MA, Van Rozen AJ, Oude Ophuis RJ, Vanderschuren LJ, Adan RA, la Fleur SE. Central melanocortins regulate the motivation for sucrose reward. PLoS One. 2015;10(3): e0121768. https://doi.org/10.1371/journal.pone.0121768