Kisspeptin-54 Ameliorates Electrocardiographic Abnormalities in an Experimental Parkinson's Rat Model

Aim: Cardiac complications may arise in association with Parkinson’s disease as age progresses. Kisspeptins are a group of peptides that mediate their physiological functions by binding to the GPR54 receptor. This study aimed to investigate whether KP-54 has an effect on the electrical activity of the heart in an animal model of Parkinson's disease. Material and Method: Sprague-Dawley rats weighing between 290–310 g were used. An experimental hemiparkinsonian rat model was generated via stereotaxic injection of the neurotoxin 6-OHDA into the right medial forebrain bundle, effectively replicating unilateral dopaminergic neuronal loss. Rats received either control (aCSF, 5 µL, ICV) or KP-54 (3 nmol/kg, ICV) treatment once daily for seven consecutive days. At the end of the seventh day, behavioral tests were conducted on the rats. Following the behavioral tests, electrocardiographic (ECG) recordings were obtained. Results: 6-OHDA significantly increased catalepsy time (p<0.001), which was effectively reduced by KP-54 (p<0.05). In the open field test (OFT), rats injected with 6-OHDA showed decreased distance traveled (p<0.001) and velocity (p<0.01) compared to controls, whereas KP-54 treatment partially improved these motor impairments (p<0.01). ECG data revealed that the heart rate (HR), impaired following 6-OHDA administration (p<0.01), returned to control levels in the 6-OHDA + KP-54 group (p<0.01). There were no notable differences between the groups regarding P duration, PR and QRS interval. However, the QT and QTc intervals were significantly increased (p<0.01) in the Parkinson’s group and were normalized to control levels in the 6-OHDA + KP-54 group (p<0.05). These findings indicate that KP-54 corrected the QT prolongation induced by 6-OHDA. Conclusion: In conclusion, the present findings suggest that alterations in HR and prolongation of the QT interval observed in Parkinson's disease could be prevented by the neuropeptide kisspeptin. Nevertheless, further research involving different administration routes is required to validate and expand upon these results.