Author/Editor		Kolmančič, Kaja; Živin, Marko; Zorović, Maja
Title		Modulation by estradiol of L-dopa-induced dyskinesia in a rat model of post-menopausal hemiparkinsonism
Type		članek
Vol. and No.		Letnik 12, št. 5
Publication year		2022
Volume		str. 1-20
ISSN		2075-1729
Language		eng
Abstract		Treatment with levodopa (L-dopa) in Parkinson’s disease (PD) leads to involuntary movements termed L-dopa-induced dyskinesia (LID). There are contradictory data about the influence of hormone therapy in female PD patients with LID and of 17-β-estradiol (E2) on animal correlates of LID-abnormal involuntary movements (AIMs). Our aim was to characterize the influence of E2 on motor impairment and AIMs in ovariectomized 6-hydroxydopamine (6-OHDA) rat model of PD. Half of the rats received empty and the other half implants filled with E2. Following the 6-OHDA surgery, the rats received daily treatment with either L-dopa or saline for 16 days. They were assessed for AIMs, contralateral rotations, and FAS. In the L-dopa-treated rats, E2 intensified and prolonged AIMs and contralateral rotations. On the other hand, it had no effect on motor impairment. Postmortem tyrosine hydroxylase immunostaining revealed an almost complete unilateral lesion of nigrostriatal dopaminergic neurons. E2 partially prevented the upregulation of striatal ΔFosB caused by dopamine depletion. L-dopa potentiated the upregulation of ΔFosB within the dopamine-depleted striatum and this effect was further enhanced by E2. We speculate that the potentiating effects of E2 on AIMs and on contralateral rotations could be explained by the molecular adaptations within the striatal medium spiny neurons of the direct and indirect striatofugal pathways.
Keywords		Parkinson’s disease ovariectomy post-menopausal hemiparkinsonism Parkinsonova bolezen ovariektomija postmenopavzalni hemiparkinsonizem