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  3. Intranasal AdipoRon improves motor function in a rat model of Parkinson's disease by promoting neurogenesis in the nigrostriatal pathway

Intranasal AdipoRon improves motor function in a rat model of Parkinson's disease by promoting neurogenesis in the nigrostriatal pathway

  • Neuropharmacology. 2025 Dec 15:281:110687. doi: 10.1016/j.neuropharm.2025.110687.
Seyed Zanyar Athari 1,  Fereshteh Farajdokht 2,  Mohammad Karimipour 3,  Mohammad Reza Alipour 4,  Gisou Mohaddes 5
Affiliations

Affiliations

  • 1 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
  • 2 Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
  • 3 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
  • 4 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: alipourmr@tbzmed.ac.ir.
  • 5 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Biomedical Education, California Health Sciences University, College of Osteopathic Medicine, Clovis, CA, USA. Electronic address: gmohaddes@chsu.edu.
PMID: 40962109 DOI: 10.1016/j.neuropharm.2025.110687
Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by drastically reduced synaptic plasticity and neurogenesis, possibly due to abnormal α-synuclein deposition. Boosting endogenous neurogenesis is a potential strategy for halting cell death and restoring brain function. AdipoRon (AR) has been shown to promote progenitor cell proliferation and differentiation in neurological disorders. This study investigated the effect of intranasal (IN) AR on neurogenesis in the nigrostriatal pathway and motor function in a rat PD model. Dopaminergic neuronal degeneration was induced by administering 6-hydroxydopamine (6-OHDA) into the left medial forebrain bundle. One week post-PD induction, hemiparkinsonian rats received either levodopa (10 mg/kg, gavage) or AR (0.1, 1, and 10 μg/rat, IN) for 21 days. To evaluate adult neurogenesis, 5-bromodeoxyuridine (BrdU) was injected for 5 days at the start of treatments. Motor functions were assessed 5 weeks post-6-OHDA injection, and the Animals were sacrificed for analysis. The number of BrdU and NeuN/BrdU positive cells in the ipsilateral substantia nigra (SN) was determined. Moreover, the density of Tyrosine Hydroxylase (TH)-positive fibers and the level of cerebral dopamine neurotrophic factor (CDNF), Zif-268, and synaptophysin (SYP) proteins were examined in the striatum. Our findings indicated that AR dose-dependently restored motor function and increased striatal CDNF, SYP, and Zif-268 protein expression in 6-OHDA-lesioned rats. Besides, AR 10 μg enhanced the number of NeuN + cells in the SN and dopaminergic fiber density (TH + terminals) in the striatum. These findings indicated that AR improved motor symptoms by promoting neurogenesis and synaptic transmission in the nigrostriatal pathway in PD rats.

Keywords

AdipoRon; CDNF; Dopaminergic neurons; Neurogenesis; Nigrostriatal pathway.

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