Intracerebroventricular delivery of an ODN peptide analog protects dopaminergic neurons and modulates miRNA expression in a mouse model of Parkinson’s disease
4 affiliations
- 1Laboratory of Neuroendocrine, Endocrine and Germinal Differentiation and Communication (NorDiC), Inserm UMR 1239, University of Rouen Normandy
- 2Laboratory of Neurophysiology, Cellular Physiopathology and Valorization of Biomolecules, LR18ES03, Faculty of Science of Tunis, University of Tunis El Manar
- 3Biological Resource Center, Inserm US 51, CNRS UAR 2026, HeRacLeS, University of Rouen Normandy
- 4Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism (Bio-PeroxIL), EA7270, University of Burgundy
Abstract
Introduction: Parkinson’s disease (PD) is characterized by progressive dopaminergic neuron degeneration, accompanied by oxidative stress, neuroinflammation and apoptosis. Octadecaneuropeptide, ODN, is an astroglia-derived neuropeptide known to exert potent antioxidant and anti‐apoptotic effects, protecting neuronal cells against oxidative damage and inflammation both in vivo and in vitro . In the present study, we investigated the neuroprotective potential of OP, an iso-active ODN analog, in an acute MPTP‐induced mouse model of PD.
Methods: Mice were assigned to four groups i.e., control, MPTP, OP, and MPTP plus OP. MPTP was administered intraperitoneally (3 × 20 mg/kg, 2‐h intervals), followed 1 h later by an intracerebroventricular injection of the OP (10 ng/10 μL). Brains were collected on day 7 for real-time PCR, Western blotting, immunohistochemistry, and Biochemical analyses.
Results and Discussion: Intracerebroventricular administration of OP significantly prevented the loss of tyrosine hydroxylase expression and mediating neuroprotective effect with stimulation of antiapoptotic gene Bcl‐2 in the substantia nigra and ventral tegmental area in MPTP‐treated mice. Moreover, OP markedly reduced MPTP‐induced oxidative damage by reducing ROS overproduction and lipid peroxidation and enhancing antioxidant catalase activity. OP also stimulated ERK1/2 phosphorylation and reduced the expression of pro‐inflammatory genes such as TNF‐α and increased IL‐10 mRNA levels. In addition, OP prevented MPTP‐induced down regulation of tight junction proteins i.e. occludin, ZO‐1 preserving blood–brain barrier (BBB) integrity. Furthermore, OP abolished MPTP‐induced dysregulation of PD‐related microRNAs including miR‐21‐3p, miR‐29a‐5p and markedly increased miR‐34b‐5p expression in nigrostriatal DA neurons. Taken together, these findings indicate that OP exerts potent neuroprotective effects by reducing oxidative stress, preserving BBB integrity, and limiting neuroinflammation and apoptosis. OP may therefore represent a promising therapeutic candidate for preventing dopaminergic neurodegeneration through modulation of key molecular pathways, including microRNAs involved in oxidative neurodegeneration.
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BibTeX
@article{bourzam2026intracerebroventricular,
title = {{Intracerebroventricular delivery of an ODN peptide analog protects dopaminergic neurons and modulates miRNA expression in a mouse model of Parkinson’s disease}},
author = {Amine Bourzam and Karthi Duraisamy and Omayma Dlimi and Mouna El Mehdi and Amine Cherif and Arnaud Arabo and Gérard Lizard and Taoufik Ghrairi and Benjamin Lefranc and Marie-Anne Le Solliec and Olfa Masmoudi-Kouki and Jérôme Leprince},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1933852},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1933852/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Intracerebroventricular delivery of an ODN peptide analog protects dopaminergic neurons and modulates miRNA expression in a mouse model of Parkinson’s disease
AU - Amine Bourzam
AU - Karthi Duraisamy
AU - Omayma Dlimi
AU - Mouna El Mehdi
AU - Amine Cherif
AU - Arnaud Arabo
AU - Gérard Lizard
AU - Taoufik Ghrairi
AU - Benjamin Lefranc
AU - Marie-Anne Le Solliec
AU - Olfa Masmoudi-Kouki
AU - Jérôme Leprince
PY - 2026
DA - 2026/10/21
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1933852
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1933852/full
AB - Introduction: Parkinson’s disease (PD) is characterized by progressive dopaminergic neuron degeneration, accompanied by oxidative stress, neuroinflammation and apoptosis. Octadecaneuropeptide, ODN, is an astroglia-derived neuropeptide known to exert potent antioxidant and anti‐apoptotic effects, protecting neuronal cells against oxidative damage and inflammation both in vivo and in vitro . In the present study, we investigated the neuroprotective potential of OP, an iso-active ODN analog, in an acute MPTP‐induced mouse model of PD. Methods: Mice were assigned to four groups i.e., control, MPTP, OP, and MPTP plus OP. MPTP was administered intraperitoneally (3 × 20 mg/kg, 2‐h intervals), followed 1 h later by an intracerebroventricular injection of the OP (10 ng/10 μL). Brains were collected on day 7 for real-time PCR, Western blotting, immunohistochemistry, and Biochemical analyses. Results and Discussion: Intracerebroventricular administration of OP significantly prevented the loss of tyrosine hydroxylase expression and mediating neuroprotective effect with stimulation of antiapoptotic gene Bcl‐2 in the substantia nigra and ventral tegmental area in MPTP‐treated mice. Moreover, OP markedly reduced MPTP‐induced oxidative damage by reducing ROS overproduction and lipid peroxidation and enhancing antioxidant catalase activity. OP also stimulated ERK1/2 phosphorylation and reduced the expression of pro‐inflammatory genes such as TNF‐α and increased IL‐10 mRNA levels. In addition, OP prevented MPTP‐induced down regulation of tight junction proteins i.e. occludin, ZO‐1 preserving blood–brain barrier (BBB) integrity. Furthermore, OP abolished MPTP‐induced dysregulation of PD‐related microRNAs including miR‐21‐3p, miR‐29a‐5p and markedly increased miR‐34b‐5p expression in nigrostriatal DA neurons. Taken together, these findings indicate that OP exerts potent neuroprotective effects by reducing oxidative stress, preserving BBB integrity, and limiting neuroinflammation and apoptosis. OP may therefore represent a promising therapeutic candidate for preventing dopaminergic neurodegeneration through modulation of key molecular pathways, including microRNAs involved in oxidative neurodegeneration.
SN - 1663-9812
ER -