Gap junction blockers attenuate beta oscillations and improve forelimb function in hemiparkinsonian rats

Phookan, Sujoy; Sutton, Alexander C.; Walling, Ian; Smith, Autumn B.; O’Connor, Katherine; Campbell, Joannalee C.; Calos, Megan; Yu, Wilson; Pilitsis, Julie G.; Brotchie, Jonathan M.; Shin, Damian S.

doi:10.1016/j.expneurol.2015.01.004

Cited by 22 publications

(25 citation statements)

References 100 publications

(144 reference statements)

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“…This is in line with our model, suggesting that a decrease in pathologically high gap junction conductance leads to a decrease in synchrony and hindered decorrelation of beta input. However, it is not known to which extent the effects seen by Phookan et al [2015] are due to blocking of neural gap junctions, as carbenoxolone and octanol also act on gap junctions between glial cells. Therefore, to validate our model, Cx36 knock-out (KO) mice would be ideally suited.…”

Section: Discussionmentioning

confidence: 99%

“…In our previous work , we showed only a very small and basic computational model of the basal ganglia, which is worked out here in detail. The idea that pallidal gap junctions contribute to synchrony in the parkinsonian basal ganglia has also been brought up by Phookan et al [2015], who used broad-band gap junction blockers in a 6-hydroxydopamine (6-OHDA) rat model of parkinsonism. Both sys-temic and local injection of carbenoxolone or octanol into GPe led to an attenuation of beta oscillations, and even an improvement of akinesia in a step test.…”

Section: Discussionmentioning

confidence: 99%

“…If pallidal gap junctions should have similar properties, regulation of gap junctional coupling by dopamine could be another way how dopamine influences basal ganglia activity. Phookan et al [2015] had a similar hypothesis: they tested the effects of gap junction blockers, both in GPe and systemically, on basal ganglia activity. In particular, beta oscillations decreased after blocking gap junctions, which can be seen as a first confirmation of the importance of gap junctions for PD.…”

Section: Are Connectivity Changes the Reason For Altered Basal Ganglimentioning

confidence: 99%

“…Since dopamine has been described to modulate gap junction conductance in the retina [Hampson et al, 1992, Li et al, 2013, it seems likely that gap junctions in the basal ganglia are sensitive to dopamine depletion in PD. Phookan et al [2015] described a depression of beta oscillations after blocking gap junctions in GPe. As broad band gap junction blockers also affect gap junction coupling between glia cells and come along with non-specific side effects, it is not clear how this relates to our results.…”

Section: Gap Junction Coupling Might Be Increased In Pdmentioning

confidence: 99%

“…It is remarkable that the GPe has a very rich intrinsic connectivity [Sadek et al, 2007], including few, but effective inhibitory synapses [Sadek et al, 2007, Bugaysen et al, 2013 and possibly also gap junctions , Phookan et al, 2015. Furthermore, particularly prominent activity changes occur in GPe after dopamine depletion.…”

Section: Introductionmentioning

confidence: 99%

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Do gap junctions regulate synchrony in the Parkinsonian basal ganglia?

Schwab¹

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Are Connectivity Changes the Reason For Altered Basal Ganglimentioning

confidence: 99%

Section: Gap Junction Coupling Might Be Increased In Pdmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Do gap junctions regulate synchrony in the Parkinsonian basal ganglia?

Schwab¹

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Increased expression of Nav1.6 of reactive astrocytes in the globus pallidus is closely associated with motor deficits in a model of Parkinson's disease

Liu

Zhang

Feng

et al. 2023

Glia

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Parkinson's disease (PD) is a common neurodegenerative disease in elderly people, which is characterized by motor disabilities in PD patients. Nav1.6 is the most abundant subtype of voltage‐gated sodium channels (VGSCs) in the brain of adult mammals and rodents. Here we investigated the role of Nav1.6 in the external globus pallidus (GP) involved in the pathogenesis of motor deficits in unilateral 6‐OHDA(6‐hydroxydopamine)lesioned rats. The results show that Nav1.6 is dramatically increased in reactive astrocytes of the ipsilateral GP in the middle stage, but not different from the control rats in the later stage of the pathological process in 6‐OHDA lesioned rats. Furthermore, the down‐regulation of Nav1.6 expression in the ipsilateral GP can significantly improve motor deficits in 6‐OHDA lesioned rats in the middle stage of the pathological process. The electrophysiological experiments show that the down‐regulation of Nav1.6 expression in the ipsilateral GP significantly decreases the abnormal high synchronization between the ipsilateral M1 (the primary motor cortex) and GP in 6‐OHDA lesioned rats. Ca2+ imaging reveals that the down‐regulation of Nav1.6 expression reduces the intracellular concentration of Ca2+ ([Ca2+]i) in primary cultured astrocytes. These findings suggest that the increased Nav1.6 expression of reactive astrocytes in the GP play an important role in the pathogenesis of motor dysfunction in the middle stage in 6‐OHDA lesioned rats, which may participate in astrocyte‐neuron communication by regulating [Ca2+]i of astrocytes, thereby contributing to the formation of abnormal electrical signals of the basal ganglia (BG) in 6‐OHDA lesioned rats.

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Na+ leak-current channel (NALCN) at the junction of motor and neuropsychiatric symptoms in Parkinson’s disease

Kasap

Dwyer

2021

J Neural Transm

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Gap junction blockers attenuate beta oscillations and improve forelimb function in hemiparkinsonian rats

Cited by 22 publications

References 100 publications

Do gap junctions regulate synchrony in the Parkinsonian basal ganglia?

Do gap junctions regulate synchrony in the Parkinsonian basal ganglia?

Increased expression of Nav1.6 of reactive astrocytes in the globus pallidus is closely associated with motor deficits in a model of Parkinson's disease

Na+ leak-current channel (NALCN) at the junction of motor and neuropsychiatric symptoms in Parkinson’s disease

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