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Article

Remodeling of Perineuronal Nets in the Striato-Cortical Axis in L-DOPA-Induced Dyskinesia Rat Model

by
Nedime Tugce Bilbay
1,2,*,
Banu Cahide Tel
3,
Gulsum Akkus
3,
Canan Cakir-Aktas
1,
Taha Solakoglu
1,
Gul Yalcin-Cakmakli
4 and
Bulent Elibol
1
1
Institute of Neurological Sciences and Psychiatry, Hacettepe University, 06100 Ankara, Türkiye
2
Neurology Department, Ministry of Health Diskapi Yildirim Beyazit Training and Research Hospital, 06110 Ankara, Türkiye
3
Department of Pharmacology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Türkiye
4
Department of Neurology, Faculty of Medicine, Hacettepe University, 06100 Ankara, Türkiye
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(23), 11726; https://doi.org/10.3390/ijms262311726
Submission received: 10 November 2025 / Revised: 1 December 2025 / Accepted: 1 December 2025 / Published: 3 December 2025
(This article belongs to the Section Molecular Neurobiology)
Review Reports Versions Notes

Abstract

L-DOPA-induced dyskinesia (LID) remains the most challenging complication of dopamine replacement therapy in Parkinson’s disease, correlated with maladaptive plasticity within corticostriatal circuits. Perineuronal nets (PNNs), extracellular matrix structures enwrapping mainly parvalbumin interneurons (PV-INs), are key regulators of neuronal stability and plasticity, yet their contribution to LID is unknown. Using a unilateral 6-hydroxydopamine rat model of Parkinsonism followed by chronic L-DOPA administration, we quantified PNN–PV associations by Wisteria floribunda agglutinin (WFA) and PV immunolabeling across striatal and motor cortical territories. Dopamine loss markedly reduced PNN density and intensity in the dorsolateral striatum (DLS), which only partially recovered after L-DOPA. In LID, canonical WFA⁺/PV⁺ cells remained low, whereas non-canonical WFA⁻/PV⁺ populations expanded in both DLS and M1 motor cortex (M1), indicating region-specific remodeling toward a high-plasticity state. To assess causality, we used Chondroitinase ABC (ChABC) for PNN degradation. DLS-targeted ChABC exacerbated abnormal involuntary movements and increased local PV density, while M1-ChABC had no behavioral effect but altered PV metrics within the DLS–M1 axis. These findings identify the DLS as a critical node where PNN fragility amplifies dyskinesia, highlight a functional coupling between striatal and cortical PNN–PV remodeling, and suggest that stabilizing extracellular matrix integrity could mitigate maladaptive plasticity underlying LID.
Keywords: Parkinson’s disease; L-DOPA induced dyskinesia; perineuronal nets; parvalbumin interneuron; WFA; ChABC; 6-OHDA rat model; striatum; cortex Parkinson’s disease; L-DOPA induced dyskinesia; perineuronal nets; parvalbumin interneuron; WFA; ChABC; 6-OHDA rat model; striatum; cortex

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MDPI and ACS Style

Bilbay, N.T.; Tel, B.C.; Akkus, G.; Cakir-Aktas, C.; Solakoglu, T.; Yalcin-Cakmakli, G.; Elibol, B. Remodeling of Perineuronal Nets in the Striato-Cortical Axis in L-DOPA-Induced Dyskinesia Rat Model. Int. J. Mol. Sci. 2025, 26, 11726. https://doi.org/10.3390/ijms262311726

AMA Style

Bilbay NT, Tel BC, Akkus G, Cakir-Aktas C, Solakoglu T, Yalcin-Cakmakli G, Elibol B. Remodeling of Perineuronal Nets in the Striato-Cortical Axis in L-DOPA-Induced Dyskinesia Rat Model. International Journal of Molecular Sciences. 2025; 26(23):11726. https://doi.org/10.3390/ijms262311726

Chicago/Turabian Style

Bilbay, Nedime Tugce, Banu Cahide Tel, Gulsum Akkus, Canan Cakir-Aktas, Taha Solakoglu, Gul Yalcin-Cakmakli, and Bulent Elibol. 2025. "Remodeling of Perineuronal Nets in the Striato-Cortical Axis in L-DOPA-Induced Dyskinesia Rat Model" International Journal of Molecular Sciences 26, no. 23: 11726. https://doi.org/10.3390/ijms262311726

APA Style

Bilbay, N. T., Tel, B. C., Akkus, G., Cakir-Aktas, C., Solakoglu, T., Yalcin-Cakmakli, G., & Elibol, B. (2025). Remodeling of Perineuronal Nets in the Striato-Cortical Axis in L-DOPA-Induced Dyskinesia Rat Model. International Journal of Molecular Sciences, 26(23), 11726. https://doi.org/10.3390/ijms262311726

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