Nasal application of kisspeptin-54 mitigates motor deficits by reducing nigrostriatal dopamine loss in hemiparkinsonian rats

Parkinson’s Disease is a progressive neurodegenerative disorder characterized by motor symptoms resulting from the loss of nigrostriatal dopaminergic neurons. Kisspeptins (KPs) are a family of neuropeptides that are encoded by the Kiss-1 gene, which exert their physiological effects through interact...

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Bibliographic Details
Published in:Behavioural brain research 2024-06, Vol.468, p.115035, Article 115035
Main Authors: Sinen, Osman, Sinen, Ayşegül Gemici, Derin, Narin, Aslan, Mutay Aydın
Format: Article
Language:English
Subjects:
Administration, Intranasal
Animals
Corpus Striatum - drug effects
Corpus Striatum - metabolism
Disease Models, Animal
Dopamine
Dopamine - metabolism
Dopaminergic Neurons - drug effects
Dopaminergic Neurons - metabolism
GPR54
Kisspeptin
Kisspeptins - administration & dosage
Kisspeptins - metabolism
Kisspeptins - pharmacology
Male
Motor Activity - drug effects
Oxidopamine - pharmacology
Parkinsonian Disorders - drug therapy
Parkinsonian Disorders - metabolism
Parkinson’s Disease
Rats
Rats, Sprague-Dawley
Substantia Nigra - drug effects
Substantia Nigra - metabolism
Tyrosine 3-Monooxygenase - metabolism
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Summary:Parkinson’s Disease is a progressive neurodegenerative disorder characterized by motor symptoms resulting from the loss of nigrostriatal dopaminergic neurons. Kisspeptins (KPs) are a family of neuropeptides that are encoded by the Kiss-1 gene, which exert their physiological effects through interaction with the GPR54 receptor. In the current investigation, we investigated the prospective protective effects of central KP-54 treatments on nigrostriatal dopaminergic neurons and consequent motor performance correlates in 6-hydroxydopamine (6-OHDA)-lesioned rats. Male adult Sprague Dawley rats underwent stereotaxic injection of 6-OHDA into the right medial forebrain bundle to induce hemiparkinsonism. Following surgery, rats received chronic central treatments of nasal or intracerebroventricular KP-54 (logarithmically increasing doses) for seven consecutive days. Motor performance was evaluated seven days post-surgery utilizing the open field test and catalepsy test. The levels of dopamine in the striatum were determined with mass spectrometry. Immunohistochemical analysis was conducted to assess the immunoreactivities of tyrosine hydroxylase (TH) and the GPR54 in the substantia nigra. The dose-response curve revealed a median effective dose value of ≈3 nmol/kg for both central injections. Due to its non-invasive and effective nature, nasal administration was utilized in the second phase of our study. Chronic administration of KP-54 (3nmol/kg, nasally) significantly protected 6-OHDA-induced motor deficits. Nasal KP-54 attenuated the loss of nigrostriatal dopaminergic neurons induced by 6-OHDA. Additionally, significant correlations were observed between motor performance and nigrostriatal dopamine levels. Immunohistochemical analysis demonstrated the localization of the GPR54 within TH-positive nigral cells. These findings suggest the potential efficacy of central KP-54 on motor impairments in hemiparkinsonism. [Display omitted] •Intranasal KP-54 treatment improves motor deficits induced by 6-OHDA.•Chronic intranasal KP-54 administration attenuates the loss of nigrostriatal dopaminergic neurons.•Enhanced motor performance correlates with higher nigrostriatal dopamine levels following KP-54 treatment.•Kisspeptin receptor (GPR54) is present in nigral dopaminergic neurons.
ISSN:0166-4328
1872-7549
1872-7549
DOI:10.1016/j.bbr.2024.115035