Chronic Nasal Administration of Kisspeptin-54 Regulates Mood-Related Disorders Via Amygdaloid GABA in Hemi-Parkinsonian Rats

Background: Depression and anxiety, the most prevalent neuropsychiatric manifestations in Parkinson’s disease (PD), negatively impact their quality of life. Aims: To determine whether the chronic nasal administration of kisspeptin-54 (KP-54) could. Alleviate symptoms of anxiety and depression in he...

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Main Authors: Osman Sinen, Ayşegül Gemici Sinen, Narin Derin, Mutay Aydın Aslan
Format: Article
Language:English
Published: Galenos Publishing House 2024-11-01
Series:Balkan Medical Journal
Online Access:https://balkanmedicaljournal.org/text.php?lang=en&id=2643
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author Osman Sinen
Ayşegül Gemici Sinen
Narin Derin
Mutay Aydın Aslan
author_facet Osman Sinen
Ayşegül Gemici Sinen
Narin Derin
Mutay Aydın Aslan
author_sort Osman Sinen
collection DOAJ
description Background: Depression and anxiety, the most prevalent neuropsychiatric manifestations in Parkinson’s disease (PD), negatively impact their quality of life. Aims: To determine whether the chronic nasal administration of kisspeptin-54 (KP-54) could. Alleviate symptoms of anxiety and depression in hemi-Parkinsonian rats. Study Design: Experimental study. Methods: This study included adult Sprague Dawley male rats who were administered either a vehicle (artificial cerebrospinal fluid) or 6-hydroxydopamine (6-OHDA) unilaterally into the medial forebrain bundle. The vehicle, or KP-54 (3 nmol/kg, applied topically to the rhinarium), was administered daily for a seven-day period. The sucrose preference test (SPT), elevated plus maze test (EPMT), and open field test (OFT) were implemented to evaluate depression- and anxiety-like behaviors, respectively, seven days following the lesion surgery. Gamma-aminobutyric acid (GABA) concentrations in the amygdala were quantified using mass spectrometry. Tyrosine hydroxylase in substantia nigra was analyzed using immunohistochemistry. Results: The nasal delivery of KP-54 significantly reduced depression- and anxiety-like behaviors that were induced by 6-OHDA, as indicated by the results of the SPT, OFT, and EPMT. Moreover, it was observed that nasal KP-54 effectively mitigated 6-OHDA-induced motor deficits and the loss of nigral dopaminergic neurons. The nasal administration of KP-54 augmented the decline in GABA levels in the amygdala induced by 6-OHDA. Furthermore, effective correlations were established between GABA concentrations and behavioral parameters. Conclusion: The nasal delivery of KP-54 could function as a viable therapeutic alternative for treating mood-related disorders in PD.
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spelling doaj-art-23baf96dd08b4edea91d117ad2c1e3792024-11-11T08:24:46ZengGalenos Publishing HouseBalkan Medical Journal2146-31232146-31312024-11-0141647648310.4274/balkanmedj.galenos.2024.2024-7-46Chronic Nasal Administration of Kisspeptin-54 Regulates Mood-Related Disorders Via Amygdaloid GABA in Hemi-Parkinsonian RatsOsman Sinen0https://orcid.org/0000-0002-3554-5604Ayşegül Gemici Sinen1https://orcid.org/0000-0002-6751-4407Narin Derin2https://orcid.org/0000-0001-5521-8929Mutay Aydın Aslan3https://orcid.org/0000-0002-0660-971XDepartment of Physiology, Akdeniz University Faculty of Medicine, Antalya, TürkiyeDepartment of Biophysics, Akdeniz University Faculty of Medicine, Antalya, TürkiyeDepartment of Biophysics, Akdeniz University Faculty of Medicine, Antalya, TürkiyeDepartment of Medical Biochemistry, Akdeniz University Faculty of Medicine, Antalya, TürkiyeBackground: Depression and anxiety, the most prevalent neuropsychiatric manifestations in Parkinson’s disease (PD), negatively impact their quality of life. Aims: To determine whether the chronic nasal administration of kisspeptin-54 (KP-54) could. Alleviate symptoms of anxiety and depression in hemi-Parkinsonian rats. Study Design: Experimental study. Methods: This study included adult Sprague Dawley male rats who were administered either a vehicle (artificial cerebrospinal fluid) or 6-hydroxydopamine (6-OHDA) unilaterally into the medial forebrain bundle. The vehicle, or KP-54 (3 nmol/kg, applied topically to the rhinarium), was administered daily for a seven-day period. The sucrose preference test (SPT), elevated plus maze test (EPMT), and open field test (OFT) were implemented to evaluate depression- and anxiety-like behaviors, respectively, seven days following the lesion surgery. Gamma-aminobutyric acid (GABA) concentrations in the amygdala were quantified using mass spectrometry. Tyrosine hydroxylase in substantia nigra was analyzed using immunohistochemistry. Results: The nasal delivery of KP-54 significantly reduced depression- and anxiety-like behaviors that were induced by 6-OHDA, as indicated by the results of the SPT, OFT, and EPMT. Moreover, it was observed that nasal KP-54 effectively mitigated 6-OHDA-induced motor deficits and the loss of nigral dopaminergic neurons. The nasal administration of KP-54 augmented the decline in GABA levels in the amygdala induced by 6-OHDA. Furthermore, effective correlations were established between GABA concentrations and behavioral parameters. Conclusion: The nasal delivery of KP-54 could function as a viable therapeutic alternative for treating mood-related disorders in PD.https://balkanmedicaljournal.org/text.php?lang=en&id=2643
spellingShingle Osman Sinen
Ayşegül Gemici Sinen
Narin Derin
Mutay Aydın Aslan
Chronic Nasal Administration of Kisspeptin-54 Regulates Mood-Related Disorders Via Amygdaloid GABA in Hemi-Parkinsonian Rats
Balkan Medical Journal
title Chronic Nasal Administration of Kisspeptin-54 Regulates Mood-Related Disorders Via Amygdaloid GABA in Hemi-Parkinsonian Rats
title_full Chronic Nasal Administration of Kisspeptin-54 Regulates Mood-Related Disorders Via Amygdaloid GABA in Hemi-Parkinsonian Rats
title_fullStr Chronic Nasal Administration of Kisspeptin-54 Regulates Mood-Related Disorders Via Amygdaloid GABA in Hemi-Parkinsonian Rats
title_full_unstemmed Chronic Nasal Administration of Kisspeptin-54 Regulates Mood-Related Disorders Via Amygdaloid GABA in Hemi-Parkinsonian Rats
title_short Chronic Nasal Administration of Kisspeptin-54 Regulates Mood-Related Disorders Via Amygdaloid GABA in Hemi-Parkinsonian Rats
title_sort chronic nasal administration of kisspeptin 54 regulates mood related disorders via amygdaloid gaba in hemi parkinsonian rats
url https://balkanmedicaljournal.org/text.php?lang=en&id=2643
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