The European journal of neuroscience
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Parkinson's disease (PD) is characterized by widespread neural interactions in cortico-basal-ganglia networks primarily in beta oscillations (approx. 10-30 Hz), as suggested by previous findings of levodopa-modulated interhemispheric coherence between the bilateral subthalamic nuclei (STN) in local field potential recordings (LFPs). However, due to confounding effects of volume conduction the existence of 'genuine' interhemispheric subcortical coherence remains an open question. To address this issue we utilized the imaginary part of coherency (iCOH) which, in contrast to the standard coherence, is not susceptible to volume conduction. ⋯ These results suggest a functional distinction between low and high beta oscillations in STN-LFP in line with previous studies. Furthermore, the observed functional coupling between the bilateral STN might contribute to the understanding of bilateral effects of unilateral deep brain stimulation. In conclusion, the present results imply a significant contribution of time-delayed neural interactions to interhemispheric coherence, and the clinical relevance of long-distance neural interactions between bilateral STN for motor symptoms in PD.
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After traumatic spinal cord injury (SCI), endoplasmic reticulum (ER) stress exacerbates secondary injury, leading to expansion of demyelination and reduced remyelination due to oligodendrocyte precursor cell (OPC) apoptosis. Although recent studies have revealed that amiloride controls ER stress and leads to improvement in several neurological disorders including SCI, its mechanism is not completely understood. Here, we used a rat SCI model to assess the effects of amiloride on functional recovery, secondary damage expansion, ER stress-induced cell death and OPC survival. ⋯ Furthermore, in vitro experiments performed to investigate the direct effect of amiloride on OPCs revealed that amiloride reduced CHOP expression in OPCs cultured under ER stress. These results suggest that amiloride controls ER stress in SCI and inhibits cellular apoptosis, contributing to OPC survival. The present study suggests that amiloride may be an effective treatment to reduce ER stress-induced cell death in the acute phase of SCI.
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We previously reported that an intraperitoneal (i.p.) injection of synthetic double-stranded RNA, polyriboinosinic:polyribocytidylic acid (poly-I:C), produced prolonged fatigue in rats, which might serve as a model for chronic fatigue syndrome. The poly-I:C-induced fatigue was associated with serotonin transporter (5-HTT) overexpression in the prefrontal cortex (PFC), a brain region that has been suggested to be critical for fatigue sensation. In the present study, we demonstrated that microglial activation in the PFC was important for poly-I:C-induced fatigue in rats, as pretreatment with minocycline, an inhibitor of microglial activation, prevented the decrease in running wheel activity. ⋯ Furthermore, direct application of poly-I:C enhanced IL-1β expression in primary microglia. We therefore propose that poly-I:C-induced microglial activation, which may be at least partly caused by a direct action of poly-I:C, enhances IL-1β expression. Then, IL-1β induces 5-HTT expression in astrocytes, resulting in the immunologically induced fatigue.
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Global cerebral ischemia following cardiac arrest and cardiopulmonary resuscitation (CA/CPR) causes injury to hippocampal CA1 pyramidal neurons and impairs cognition. Small conductance Ca(2+)-activated potassium channels type 2 (SK2), expressed in CA1 pyramidal neurons, have been implicated as potential protective targets. Here we showed that, in mice, hippocampal long-term potentiation (LTP) was impaired as early as 3 h after recovery from CA/CPR and LTP remained impaired for at least 30 days. ⋯ Further, patch-clamp experiments demonstrated no change in functional synaptic NMDA receptors at 7 or 30 days after CA/CPR. Electrophysiology recordings showed that synaptic SK channel activity was reduced for the duration of experiments performed (up to 30 days) and that, surprisingly, treatment with 1-EBIO did not prevent the CA/CPR-induced loss of synaptic SK channel function. We concluded that CA/CPR caused alterations in post-synaptic signaling that were prevented by treatment with the SK2 agonist 1-EBIO, indicating that activators of SK2 channels may be useful therapeutic agents to prevent ischemic injury and cognitive impairments.
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Probenecid, an agonist of transient receptor vanilloid (TRPV) type 2, was used to evaluate the effects of TRPV2 activation on excitatory and inhibitory synaptic transmission in the dorsal horn (DH) of the rat spinal cord and on nociceptive reflexes induced by thermal heat and mechanical stimuli. The effects of probenecid were compared with those of capsaicin, a TRPV1 agonist. Calcium imaging experiments on rat dorsal root ganglion (DRG) and DH cultures indicated that functional TRPV2 and TRPV1 were expressed by essentially non-overlapping subpopulations of DRG neurons, but were absent from DH neurons and DH and DRG glial cells. ⋯ Capsaicin induced both mechanical hyperalgesia/allodynia and heat hyperalgesia. Activation of TRPV1 or TRPV2 in distinct sets of primary afferents increased the sEPSC frequencies in a largely common population of DH neurons in laminae III-V, and might underlie the development of mechanical hypersensitivity following probenecid or capsaicin treatment. However, only TRPV1-expressing afferents facilitated excitatory and/or inhibitory transmission in a subpopulation of lamina II neurons, and this phenomenon might be correlated with the induction of thermal heat hyperalgesia.