Short-term hindlimb unloading negatively affects dopaminergic transmission in the nigrostriatal system of mice.

Autor: Naumova AA; Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russia., Oleynik EA; Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russia., Khramtsova AV; Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russia., Nikolaeva SD; Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russia., Chernigovskaya EV; Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russia., Glazova MV; Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, Russia.
Jazyk: angličtina
Zdroj: Developmental neurobiology [Dev Neurobiol] 2023 Jul-Sep; Vol. 83 (5-6), pp. 205-218. Date of Electronic Publication: 2023 Jul 24.
DOI: 10.1002/dneu.22924
Abstrakt: The nigrostriatal system composed of the dorsal striatum and the substantia nigra (SN) is highly involved in the control of motor behavior. Various extremal and pathological conditions as well as social isolation (SI) may cause an impairment of locomotor function; however, corresponding alterations in the nigrostriatal dopaminergic pathway are far from full understanding. Here, we analyzed the effect of 3-day hindlimb unloading (HU) and SI on the key players of dopamine transmission in the nigrostriatal system of CD1 mice. Three groups of mice were analyzed: group-housed (GH), SI, and HU animals. Our data showed a significant decrease in the expression and phosphorylation of tyrosine hydroxylase (TH) in the SN and dorsal striatum of HU mice that suggested attenuation of dopamine synthesis in response to HU. In the dorsal striatum of HU mice, the downregulation of TH expression was also observed indicating the effect of unloading; however, TH phosphorylation at Ser40 was mainly affected by SI pointing on an impact of isolation too. Expression of dopamine receptors D1 in the dorsal striatum of HU mice was increased suggesting a compensatory response, but the activity of downstream signaling pathways involving protein kinase A and cAMP response element-binding protein was inhibited. At the same time, SI alone did not affect expression of DA receptors and activity of downstream signaling in the dorsal striatum. Obtained data let us to conclude that HU was the main factor which impaired dopamine transmission in the nigrostriatal system but SI made some contribution to its negative effects.
(© 2023 Wiley Periodicals LLC.)
Databáze: MEDLINE
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