Electroacupuncture Alleviates Motor Symptoms and Up-Regulates Vesicular Glutamatergic Transporter 1 Expression in the Subthalamic Nucleus in a Unilateral 6-Hydroxydopamine-Lesioned Hemi-Parkinsonian Rat Model.

Previous studies have shown that electroacupuncture (EA) promotes recovery of motor function in Parkinson's disease (PD). However the mechanisms are not completely understood. Clinically, the subthalamic nucleus (STN) is a critical target for deep brain stimulation treatment of PD, and vesicular glutamate transporter 1 (VGluT1) plays an important role in the modulation of glutamate in the STN derived from the cortex. In this study, a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD was treated with 100 Hz EA for 4 weeks. Immunohistochemical analysis of tyrosine hydroxylase (TH) showed that EA treatment had no effect on TH expression in the ipsilateral striatum or substantia nigra pars compacta, though it alleviated several of the parkinsonian motor symptoms. Compared with the hemi-parkinsonian rats without EA treatment, the 100 Hz EA treatment significantly decreased apomorphine-induced rotation and increased the latency in the Rotarod test. Notably, the EA treatment reversed the 6-OHDA-induced down-regulation of VGluT1 in the STN. The results demonstrated that EA alleviated motor symptoms and up-regulated VGluT1 in the ipsilateral STN of hemi-parkinsonian rats, suggesting that up-regulation of VGluT1 in the STN may be related to the effects of EA on parkinsonian motor symptoms via restoration of function in the cortico-STN pathway.

Pathway-Specific Remodeling of Thalamostriatal Synapses in Parkinsonian Mice.

Movement suppression in Parkinson's disease (PD) is thought to arise from increased efficacy of the indirect pathway basal ganglia circuit, relative to the direct pathway. However, the underlying pathophysiological mechanisms remain elusive. To examine whether changes in the strength of synaptic inputs to these circuits contribute to this imbalance, we obtained paired whole-cell recordings from striatal direct- and indirect-pathway medium spiny neurons (dMSNs and iMSNs) and optically stimulated inputs from sensorimotor cortex or intralaminar thalamus in brain slices from control and dopamine-depleted mice. We found that dopamine depletion selectively decreased synaptic strength at thalamic inputs to dMSNs, suggesting that thalamus drives asymmetric activation of basal ganglia circuitry underlying parkinsonian motor impairments. Consistent with this hypothesis, in vivo chemogenetic and optogenetic inhibition of thalamostriatal terminals reversed motor deficits in dopamine-depleted mice. These results implicate thalamostriatal projections in the pathophysiology of PD and support interventions targeting thalamus as a potential therapeutic strategy.

Electro-acupuncture stimulation improves motor disorders in Parkinsonian rats.

Electro-acupuncture (EA) is believed to be effective for alleviating motor symptoms in patients with Parkinson's disease. In a rat hemiparkinsonian model induced by unilateral transection of the medial forebrain bundle (MFB), the effects of EA stimulation were investigated. EA stimulation at a high frequency (100 Hz) significantly reduced apomorphine-induced rotational behavior. Tyrosine hydroxylase immunohistochemical staining revealed that EA at 100 Hz protected axotomized dopaminergic neurons from degeneration in the substantia nigra (SN). Moreover, high frequency EA reversed the axotomy-induced decrease in substance P content and increase in glutamate decarboxylase-67 (GAD 67) mRNA level in the midbrain; however, it did not affect the axotomy-induced increase in enkephalin content in the globus pallidus. These results suggest that the effects of high frequency EA on motor symptoms of Parkinsonian rats may involve restoration of the homeostasis of dopaminergic transmission in the basal ganglia circuit.

Electro-acupuncture stimulation protects dopaminergic neurons from inflammation-mediated damage in medial forebrain bundle-transected rats.

Through producing a variety of cytotoxic factors upon activation, microglia are believed to participate in the mediation of neurodegeneration. Intervention against microglial activation may therefore exert a neuroprotective effect. Our previous study has shown that the electro-acupuncture (EA) stimulation at 100 Hz can protect axotomized dopaminergic neurons from degeneration. To explore the underlying mechanism, the effects of 100 Hz EA stimulation on medial forebrain bundle (MFB) axotomy-induced microglial activation were investigated. Complement receptor 3 (CR3) immunohistochemical staining revealed that 24 sessions of 100 Hz EA stimulation (28 days after MFB transection) significantly inhibited the activation of microglia in the substantia nigra pars compacta (SNpc) induced by MFB transection. Moreover, 100 Hz EA stimulation obviously inhibited the upregulation of the levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta mRNA in the ventral midbrains in MFB-transected rats, as revealed by reverse transcriptase polymerase chain reaction (RT-PCR). ED1 immunohistochemical staining showed that a large number of macrophages appeared in the substantia nigra (SN) 14 days after MFB transection. The number of macrophages decreased by 47% in the rats that received 12 sessions of EA simulation after MFB transection. These data indicate that the neuroprotective role of 100 Hz EA stimulation on dopaminergic neurons in MFB-transected rats is likely to be mediated by suppressing axotomy-induced inflammatory responses. Taken together with our previous results, this study suggests that the neuroprotective effect of EA on the dopaminergic neurons may stem from the collaboration of its anti-inflammatory and neurotrophic actions.

Electro-acupuncture improves behavior and upregulates GDNF mRNA in MFB transected rats.

Low and high frequency electro-acupuncture (EA) stimulation was used in rats that had been lesioned by medial forebrain bundle transection. Behavioral tests showed that both low and high frequency EA stimulation significantly reduced the amphetamine-induced rotation 2 weeks after the lesion but only high frequency EA improved the rotational behavior at 4 weeks. Analysis of the dopamine content in the striatum did not show any significant change after EA. In situ hybridization showed that high frequency EA stimulation up-regulated the glial cell line-derived neurotrophic factor (GDNF) mRNA in both sides of the globus pallidus, while low frequency EA only affected the unlesioned side. It suggests that the retrograde nourishment of GDNF to the dopaminergic neurons and the balanced activity of different nuclei in the basal ganglia circuit after EA may contribute to the behavioral improvement in these rats, which might be the factors that underlie the effectiveness of EA in the treatment of Parkinson's disease.

[Effect of injuries of the median forebrain bundle and the preoptic area on the activity of the strychnine-induced epileptiform focus (concerning the phenomenon of the hyperactive determinant transmission center)]. / Vliianie povrezhdenii zony medial'nogo puchka perednego mozga i preopticheskoi oblasti na aktivnost' vyzvannogo strikhninom epileptiformnogo ochaga (k fenomenu giperaktivnoi determiniruiushchei stantsii otpravleniia.

It was shown in experiments on cats that a lesion of the medial forebrain bundle (MFB) and partly of the preoptic region (RPO) at the side of local strychnine application of the cortex (g. suprasylvius medius) resulted in depression of the epileptiform activity in the strychnine-induced focus, as well as in the second "mirror" focus appearing in the symmetrical cortical area of the other hemisphere. This effect could also be obtained under conditions of injury of the MFB alone. The lesion of the MFB and partly of the RPO at the side of the "Mirror" focus leads to depression of the spike potentials in this focus only and does not influence the activity in the primary epileptiform focus. The described effects are considered from the aspect of conceptions of the role played by the determinant dispatch station (DDS) in the central nervous system activity: the primary epileptiform focus plays the role of the hyperactive DDS which induces the development of the secondary foci and maintaines and determines the character of their activity. The results of these studies suggest the participation of the MFB in the modulation of the epileptiform activity in the cortex.