Conclusion
Results of the present study suggested that dysregulation of the
dopaminergic system in the substantia nigra was mainly associated with
HU, whereas in the dorsal striatum both HU and SI contributed to the
attenuation of dopamine signaling. We demonstrated that HU significantly
impaired activity of TH indicating a decrease in dopamine synthesis in
the nigrostriatal system of mice. In turn, reduced dopamine innervation
was accompanied with significant reduction in the activity of PKA and
transcriptional factor CREB in the dorsal striatum that, in hence,
pointed on decrease in the activity of striatal cells. At the same time
SI itself only decreased TH activity in the striatum, while no changes
in dopamine-related signaling was observed.
Noteworthy, HU and SI are abnormal states which can induce stress
responses (Globus & Morey-Holton, 2016; Mumtaz et al. , 2018;
Tahimic et al. , 2019). However, the studies suggested that, while
acute stress (hours) elevated synthesis and release of the nigrostriatal
dopamine, chronic stress (days) exerted no effect (Abercrombie et
al. , 1989; Castro & Zigmond, 2001; Baik, 2020). Thus, the effect of HU
on dopamine transmission in the nigrostriatal system observed in the
present work was more likely associated with a loss of sensorimotor
stimuli and partial muscle disuse, while SI-induced dysregulation could
be caused mainly by a decrease in locomotor activity associated with the
absence of cage-mates. Nevertheless, further investigations are needed
to distinguish the effects of muscle unloading and social isolation more
precisely. In addition, analysis of long-term effects of these factors
on the nigrostriatal system should be performed to trace the dynamics of
changes that can be associated with development of locomotor disorders.