Brain research
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Extracellular acidosis is a common feature in pain-generating pathological conditions. Acid-sensing ion channels (ASICs), pH sensors, are distributed in peripheral sensory neurons and participate in nociception. Morphine exerts potent analgesic effects through the activation of opioid receptors for various pain conditions. ⋯ Finally, peripheral applied morphine relieved pain evoked by intraplantar of acetic acid in rats. Our results indicate that morphine can inhibit the activity of ASICs via μ-opioid receptor and cAMP dependent signal pathway. These observations demonstrate a cross-talk between ASICs and opioid receptors in peripheral sensory neurons, which was a novel analgesic mechanism of morphine.
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The underlying causes of postoperative cognitive decline (POCD) in old patients remained unelucidated, and there are little descriptions on mechanisms associated with the blood-brain barrier (BBB) disruption during POCD. We therefore tested the effects of orthopedic surgery with different concentrations of sevoflurane for 2 h on the behavior test and the BBB permeability in aged rats. 18-month rats were divided into control group and surgical group with propofol anesthesia (0.7 mgkg(-1) min(-1)) and 1.0 MAC, 1.3 MAC, and 1.5 MAC sevoflurane inhalation for 2 h. We assessed their cognitive function via Y-maze and fear conditioning test on day 1, 3, and 7 after experiments. ⋯ Surgery impaired cognitive function and increased Evans blue leakage into the hippocampus in aged rats while 2 h of 1.5 MAC sevoflurane inhalation potentiated these effects. Surgery induced occludin protein expression decreases and MMP-2,9 proteins increase and these influences can be enhanced by high concentration of sevoflurane inhalation. In conclusion, 1.5 MAC sevoflurane for 2 h exacerbated cognitive impairment induced by orthopedic surgery in aged rats and the breach in BBB may be involved in this process.
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Electrical synapses (gap junctions) exist in many types of neurons in the mammalian brain, especially during early development period; one of the most important roles of electrical synapses is to mediate the synchrony of the neuronal networks and to coordinate the neural circuits function precisely. Previous reports show that electrical coupling is involved in modulating synchronous activity among coupled neurons, but related dynamics and mechanisms are still poorly understood. Here, in order to investigate the correlation between gap junctions and synchrony we focus on the electrically coupled neurons in suprachiasmatic nucleus (SCN) by using calcium imaging with two-photon microscopy and electrophysiology. ⋯ Modification of coupling efficiency of electrical synapses changes the synchrony level of the neuronal networks in the SCN. Our results provide new insights into the causal relationship between gap junctions and synchrony in the SCN. We further demonstrate the importance of VIP in coordinating the gap junctions-mediated signal transmission and implicate that a homeostasis environment is important for SCN to modulate the rhythmic circadian activities.
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Repeated blast exposures commonly induce traumatic brain injury (TBI) characterized by diffuse axonal injury (DAI). We hypothesized that degradation of cytoskeletal proteins in the brain can lead to DAI, and evaluated α-II spectrin degradation in the pathophysiology of blast-induced TBI using the tightly-coupled three repetitive blast exposure mice model with a 1-30 min window in between exposures. Degradation of α-II spectrin and the expression profiles of caspase-3 and calpain-2, the major enzymes involved in the degradation were analyzed in the frontal cortex and cerebellum using Western blotting with specific antibodies. ⋯ The expression of another α-II spectrin degrading enzyme, calpain-2, showed a rapid increase in the frontal cortex after blast exposure and it was significantly higher in the cerebellum at later time points. Neuropathological analysis showed significant levels of DAI at the frontal cortex and cerebellum at multiple time points after repeated blast injury. In summary, repeated blast exposure results in specific degradation of α-II spectrin in the brain along with differential expression of caspase-3/calpain-2 suggesting cytoskeletal breakdown as a possible contributor of DAI after repeated blast exposure.
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Peripheral polyneuropathy is a frequent complication of diabetes. One of its consequences is neuropathic pain which is often chronic and difficult to treat. This pain management classically involves anticonvulsant drugs or tricyclic antidepressant drugs (TCA). ⋯ Chronic but not acute treatment with nortriptyline alleviates allodynia caused by the diabetic neuropathy. This effect depends on β2 adrenoceptors but not on α2 adrenoceptors, as shown by the blockade with repeated co-administration of the β2 adrenoceptor antagonist ICI118551 but not with repeated co-administration of the α2 adrenoceptor antagonist yohimbine. Direct stimulation of β2 adrenoceptors appears sufficient to relieve allodynia, as shown with chronic terbutaline treatment. δ but not mu opioid receptors seem important to these action since acute naltrindole, but not acute naloxonazine, reverses the effect of chronic nortriptyline or terbutaline treatment.