Brain research
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MicroRNAs are abundantly expressed in the brain and play an important role in disorders of the brain, including cognitive impairment and Alzheimer's disease (AD). A growing body of evidence suggests that the janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway plays a key role in the pathogenesis of AD. However, it is unclear whether miRNAs are involved in this process. ⋯ STAT3 and phospho-STAT3 protein expression was upregulated or downregulated by a miR-106a inhibitor or miR-106a mimic, respectively, indicating that miR-106a negatively regulates STAT3. Luciferase reporter gene assays confirmed that miR-106a directly targets the 3' untranslated region (UTR) of STAT3. This study suggests that miR-106a negatively regulates STAT3 activation, and also that miR-106a may provide a marker of onset or potential therapeutic target for cognitive disturbances.
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Peripheral neuropathy is a common complication of diabetes and is often accompanied by episodes of pain. There is evidence that diabetic neuropathy may affect the trigeminal nerve, altering the transmission of orofacial sensory information. Structural changes in the trigeminal ganglia may be involved in the development of these sensory alterations. ⋯ Pregabalin treatment (30mg/kg, p.o.) of diabetic rats resulted in marked and prolonged (up to 6h) reduction of heat and cold orofacial hyperalgesia. Likewise, morphine treatment (2.5mg/kg, s.c.) abolished orofacial heat and cold hyperalgesia, but its effect was significant only up to 1h after the administration. In conclusion, the results of the present study demonstrated that streptozotocin-treated rats developed long-lasting orofacial heat and cold hyperalgesia, which is more amenable to reduction by pregabalin than morphine.
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Peripheral and spinal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a key role in neuropathic pain by regulating neuronal excitability. HCN channels are expressed in the ventral-lateral periaqueductal gray (vlPAG), a region that is important for pain modulation. However, the role of vlPAG HCN channels in neuropathic pain remains poorly understood. ⋯ In addition, forskolin, which can elevate intracellular cAMP, mimics the CCI induced changes in neuronal excitability in the vlPAG. The effects of forskolin were also reversed by ZD7288. Taken together, the present data indicate an important role for HCN channels in the vlPAG in neuropathic pain.
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Several clinical and animal studies of different pain models reported that motor cortex stimulation (MCS) has an antinociceptive effect. In our previous study, the response of the primary somatosensory cortex (SI) to peripheral stimuli decreased after MCS. The aim of the present study was to investigate involvement of the periaqueductal gray (PAG) in this inhibitory effect of MCS. ⋯ Application of a nonspecific dopamine receptor antagonist (α-flupenthixol) to the PAG also blocked the inhibition of SEPs after MCS. Inhibition of SEPs after MCS was blocked by local application of a D1 antagonist (SCH-23390) in the PAG, but not by a D2 antagonist (eticlopride). These results suggest that the PAG participates in the inhibitory effect of MCS, and this effect of MCS may be mediated by opioid and dopamine D1 receptors within thePAG.
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Reliable animal models of traumatic brain injury (TBI) are essential to test novel hypotheses and therapeutic interventions. In this study, based on advantages of both the closed head injury (CHI) and controlled cortical impact (CCI) models, we developed a bilateral head injury model in mice. C57BL/6 mice were used in this study. ⋯ Furthermore, an adhesive removal test revealed significant increases in time-to-contact and time-to-remove the adhesive tape from the paw in a severity-dependent manner, indicating that our TBI model produced graded somatosensory and motor deficits. Histological analysis presented a clear gradation in brain tissue damage following graded brain injuries. These findings collectively suggest that the current model may offer a sensitive, reliable and clinically-relevant model for assessments of therapeutic strategies forTBI.