Neuroscience
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PreBötzinger complex (preBötC) neurons in the brainstem underlie respiratory rhythm generation in vitro. As a result of network interactions, preBötC neurons burst synchronously to produce rhythmic premotor inspiratory activity. Each inspiratory neuron has a characteristic 10-20 mV, 0.3-0.8 s synchronous depolarization known as the inspiratory drive potential or inspiratory envelope, topped by action potentials (APs). ⋯ We promoted the depletion of intracellular Ca(2+) stores by a transient bath application of 30 mM K(+) (high K(+)) in the continuous presence of thapsigargin or CPA. After washing out the high K(+), respiratory rhythm period and amplitude returned to baseline values. These results show that after inhibition of SERCA and depletion of intracellular Ca(2+) stores, respiratory rhythm remains substantially the same, suggesting that this source of Ca(2+) does not significantly contribute to rhythm generation in the preBötC in vitro.
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Human and animal model studies have linked brain-derived neurotrophic factor (BDNF) with the etiology of anxiety disorders. This pleiotropic neurotrophin and its receptor, TrkB, promote neuronal survival, differentiation and synaptic plasticity. Here we interrogated the role of BDNF in serotonergic neurotransmission in the basolateral amygdala (BLA), a limbic brain region associated with the neurobiology of anxiety. ⋯ These changes were associated with decreased expression of 5-HT(2) receptors. Collectively, the results indicate a required role of BDNF in serotonin transmission in the BLA. Furthermore, they suggest a mechanism underlying the reported increase in anxiety-like behavior elicited by perturbed BDNF signaling.
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Microcirculatory dysfunction may contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Using a prechiasmatic injection model, this study investigated ultrastructural changes in microvessels in brain parenchyma to determine the nature of the microthromboemboli, the involvement of nitric oxide (NO) and P-selectin in their formation, and relationship to brain injury after SAH. Brains were examined by electron microscopy (EM) and immunohistochemistry. ⋯ This correlated with decreased NO in the brain. In conclusion, SAH causes microthrombosis and constriction of arterioles, which correlates with neuronal cell death. Increased P-selectin and decreased NO suggest a mechanism for microthrombosis and arteriolar constriction.
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Glutamate homeostasis and microglia activation play an important role in the development and maintenance of neuropathic pain. So far, there has been insufficient data on the relationship between glutamate transporters and cytokines in neuropathic pain. This investigation was designed to evaluate the interaction between co-administration of ceftriaxone, a specific GLT1 activator and minocycline, a specific microglia inhibitor, on the mechanical and cold allodynia of chronic constriction injury model (CCI) in rats. ⋯ TNF-α and IL-1β increased in the spinal cord of CCI animals on days 3, 7 and 14 post-surgery. Production of studied cytokines was significantly attenuated after treatment with ceftriaxone alone and in combination with minocycline compared with control group. It is suggested that combination of these classes of drugs would be a promising approach for treatment of chronic neuropathic pain.