Dataset Information

Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson's Disease.

ABSTRACT: Recent evidence points to a neuroprotective action of bee venom on nigral dopamine neurons in animal models of Parkinson's disease (PD). Here we examined whether bee venom also displays a symptomatic action by acting on the pathological functioning of the basal ganglia in rat PD models. Bee venom effects were assessed by combining motor behavior analyses and in vivo electrophysiological recordings in the substantia nigra pars reticulata (SNr, basal ganglia output structure) in pharmacological (neuroleptic treatment) and lesional (unilateral intranigral 6-hydroxydopamine injection) PD models. In the hemi-parkinsonian 6-hydroxydopamine lesion model, subchronic bee venom treatment significantly alleviates contralateral forelimb akinesia and apomorphine-induced rotations. Moreover, a single injection of bee venom reverses haloperidol-induced catalepsy, a pharmacological model reminiscent of parkinsonian akinetic deficit. This effect is mimicked by apamin, a blocker of small conductance Ca2+-activated K+ (SK) channels, and blocked by CyPPA, a positive modulator of these channels, suggesting the involvement of SK channels in the bee venom antiparkinsonian action. In vivo electrophysiological recordings in the substantia nigra pars reticulata (basal ganglia output structure) showed no significant effect of BV on the mean neuronal discharge frequency or pathological bursting activity. In contrast, analyses of the neuronal responses evoked by motor cortex stimulation show that bee venom reverses the 6-OHDA- and neuroleptic-induced biases in the influence exerted by the direct inhibitory and indirect excitatory striatonigral circuits. These data provide the first evidence for a beneficial action of bee venom on the pathological functioning of the cortico-basal ganglia circuits underlying motor PD symptoms with potential relevance to the symptomatic treatment of this disease.

SUBMITTER: Maurice N

PROVIDER: S-EPMC4646345 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson's Disease.

Maurice Nicolas N Deltheil Thierry T Melon Christophe C Degos Bertrand B Mourre Christiane C Amalric Marianne M Kerkerian-Le Goff Lydia L

PloS one 20151116 11

Recent evidence points to a neuroprotective action of bee venom on nigral dopamine neurons in animal models of Parkinson's disease (PD). Here we examined whether bee venom also displays a symptomatic action by acting on the pathological functioning of the basal ganglia in rat PD models. Bee venom effects were assessed by combining motor behavior analyses and in vivo electrophysiological recordings in the substantia nigra pars reticulata (SNr, basal ganglia output structure) in pharmacological (n ...[more]

PMID: 26571268

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Project description:The gating of movement depends on activity within the cortico-striato-thalamic loops. Within these loops, emerging from the cells of the striatum, run two opponent pathways-the direct and indirect basal ganglia pathways. Both are complex and polysynaptic, but the overall effect of activity within these pathways is thought to encourage and inhibit movement, respectively. In Huntington's disease, the preferential early loss of striatal neurons forming the indirect pathway is thought to lead to disinhibition, giving rise to the characteristic motor features of the condition. But early Huntington's disease is also associated with apathy, a loss of motivation and failure to engage in goal-directed movement. We hypothesized that in Huntington's disease, motor signs and apathy may be selectively correlated with indirect and direct pathway dysfunction, respectively. We used spectral dynamic casual modelling of resting-state functional MRI data to model effective connectivity in a model of these cortico-striatal pathways. We tested both of these hypotheses in vivo for the first time in a large cohort of patients with prodromal Huntington's disease. Using an advanced approach at the group level we combined parametric empirical Bayes and Bayesian model reduction procedures to generate a large number of competing models and compare them using Bayesian model comparison. With this automated Bayesian approach, associations between clinical measures and connectivity parameters emerge de novo from the data. We found very strong evidence (posterior probability > 0.99) to support both of our hypotheses. First, more severe motor signs in Huntington's disease were associated with altered connectivity in the indirect pathway components of our model and, by comparison, loss of goal-direct behaviour or apathy, was associated with changes in the direct pathway component. The empirical evidence we provide here demonstrates that imbalanced basal ganglia connectivity may play an important role in the pathogenesis of some of commonest and disabling features of Huntington's disease and may have important implications for therapeutics.

Dataset Information

Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson's Disease.

Publications

Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson's Disease.

Similar Datasets

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