Vasomotor changes in the striatum associated with levodopa-induced dyskinesia in parkinsonian rat model
Abstract: Levodopa (LD) is the most beneficial treatment for motor symptoms of Parkinson’s disease (PD). Nevertheless, around half of the treated patients develop levodopa-induced dyskinesia (LID) as an adverse effect. The exact mechanism and main cause of LID remain obscure. In the same time, a growing body in the literature indicates that there are abnormal hemodynamic activities and abnormal neurovascular control in PD patients, and animal models as well. In the present brain slices study, we tested the vasomotor responses induced by dopamine (DA) in arterioles within the striatum of 6-hydroxydopamine (6-OHDA) lesioned rats. Moreover, we monitored the astrocytic Ca2+ activity in relation to these vasomotor changes in striatum of juvenile rats. Here, we directly visualized the changes in vessels diameter and Ca2+ signals by using the two-photon laser scanning microscopy (TPLSM). We found that the vasomotor responses get significantly altered by showing highest vasodilatory response in rats that show LID-like signs comparing to the Non-LID, LD naïve 6-OHDA lesioned, and unlesioned control rats. Also, we found that the vasomotor responses are determined by the changes in Ca2+ dynamics of the adjacent astrocytes. Indeed, we found a novel finding, which was an opposing coloration between the astrocytic Ca2+ signals and the following diameter changes. We concluded that DA in normal condition is an adjustor of the cerebral blood flow (CBF). However, due to the hyper-sensitivity of DA receptors (potentially in the astrocytes) and the neurovascular decoupling in LID case, there is an abnormal vasodilatory response that induces high entrance of DA to the striatum and causes an exaggerated fluctuation DA level and dyskinetic onset as a consequence.
Astrocytic Ca2+ signaling, Levodopa induced dyskinesia, Parkinsonian rat model, Two-photon laser microscopy, Vasomotor responses