Objective: To evaluate changes in non-synaptic mechanisms associated with the procedures to reproduce the neurophysiological conditions typical of Parkinson’s disease (PD).

Background: Many mechanisms that regulate synchronism processes have been related to symptoms in PD [1]. The synaptic mechanisms involved in PD have been investigated, however, non-synaptic mechanisms, such as gap-junctions (GJ) and hemichannels of connexins, with an important role on neuronal synchronism and excitability [2], remain poorly investigated. Studies have shown that GJ can affect synchronization with an impact on the firing rate across the neural network [3]. In human tissue, the death of dopaminergic neurons leads to the remodeling of connexins 36 (Cx36). Coupling mediated by these proteins, in the cortex and striatum, contributes to PD, however, the impact of this mechanism on lesions of the nigrostriatal pathways has not yet been elucidated [4].

Method: Male Wistar rats, 3 months old, were divided into two groups: DP24 (n = 8, submitted to unilateral stereotaxic injection of 24µg of 6-OHDA, in the striatum) and Control (n = 8, replacement of 6- OHDA by 0.9% saline). After 15 days the brains were sectioned and stained by immunofluorescence against Cx36 and analyzed using confocal microscopy

Results: The lesions of the nigrostriatal pathways caused by 6-OHDA induced a significant increase in immunoreactivity to connexin 36, both in the lesion region and in the contralateral regions, when compared to the Controls. Through optical densitometry analysis, the histograms of the pixel fractions by area of ​​the confocal photomicrographs were constructed and the ipsilateral, contralateral and control regions were compared. The results of the one-way analysis of variance confirmed the significant difference between the areas assessed. Even the contralateral region suffered a positive modulation in the expression of Cx36 due to the injection of 6-OHDA.

Conclusion: Considering that the GJs act on the synchronism associated with PD, the results suggest investigating drugs that act on Cx36 aiming at the treatment of PD.

References: [1] Rubchinsky, L.L., Park, C. & Worth, R.M. Intermittent neural synchronization in Parkinson’s disease. Nonlinear Dyn 68, 329–346 (2012). https://doi.org/10.1007/s11071-011-0223-z [2] Rodrigues, A.M. , Santos, L.E.C. , Covolan, L. , Hamani, C., Almeida, A.C.G. pH during non-synaptic epileptiform activity—computational simulations. Phys. Biol. 12 (2015) 056007 [3] Hjorth, J., Blackwell, K.T., Kotaleski, J.H. Gap Junctions between Striatal Fast-Spiking Interneurons Regulate Spiking Activity and Synchronization as a Function of Cortical Activity. The Journal of Neuroscience, April 22, 2009 • 29(16):5276 –5286. [4] Schwab, B.C., Heida, T., Zhao, Y., van Gils, S.A., van Wezel, R.J. Pallidal Gap Junctions-Triggers of Synchrony in Parkinson’s Disease? Movement Disorders, Vol. 29, No. 12, 2014. doi: 10.1002/mds.25987. Epub 2014 Aug 13.

« Back to MDS Virtual Congress 2020

MDS Abstracts - https://www.mdsabstracts.org/abstract/increased-expression-of-conexin-36-in-rodent-model-of-parkinson-disease/