Neuroscience
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A role of neuropeptides in neuropathic pain development has been implicated; however, the neuroimmune interactions that are involved in the underlying mechanisms may be more important than previously thought. To examine a potential role of relations between glia cells and neuropeptides in neuropathic pain, we performed competitive reverse-transcription polymerase chain reaction (RT-PCR) from the dorsal lumbar spinal cord and the dorsal root ganglion (DRG) after chronic constriction injury (CCI) in the rat sciatic nerve. The RT-PCR results indicated that complement component 1, q subcomponent (C1q) mRNA expression was higher than glial fibrillary acidic protein (GFAP) in the spinal cord 3 and 7 days post-CCI, suggesting that spinal microglia and perivascular macrophages are more activated than astrocytes. ⋯ We thus provide novel findings that inhibition of C1q-positive cells by minocycline can diminish injury-induced neuropeptide changes in the DRG. This suggests that immune cells-derived pronociceptive factors may influence opioid peptide expression. Therefore, the injury-induced activation of microglia and leukocytes and the subsequent activation of neuropeptides involved in nociception processes are potential targets for the attenuation of neuropathic pain.
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The role of human medial temporal structures in fear conditioning has led to the suggestion that neurons in these structures might respond to painful stimuli. We have now tested the hypothesis that recordings from these structures will demonstrate potentials related to the selective activation of cutaneous nociceptors by a painful laser stimulus (laser evoked potential, LEP) (Kenton B, Coger R, Crue B, Pinsky J, Friedman Y, Carmon A (1980) Neurosci Lett 17:301-306). Recordings were carried out through electrodes implanted bilaterally in these structures for the investigation of intractable epilepsy. ⋯ Stimulus evoked changes in theta activity were observed at contacts on the right at which isolated early negative LEPs (N2*) responses could be recorded. Contacts at which LEPs could be recorded were as commonly located in medial temporal structures with evidence of seizure activity as on those without. These results demonstrate the presence of pain-related inputs to the medial temporal lobe where they may be involved in associative learning to produce anxiety and disability related to painful stimuli.
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For the efficient transfer of information across neural circuits, the number of synaptic components at synapses must be appropriately regulated. Here, we found that postsynaptic calcium/calmodulin dependent protein kinase II (CaMKII) modulates the localization of glutamate receptors (GluRs) at Drosophila larval neuromuscular junctions (NMJs). Expression of an inhibitory peptide of CaMKII, Ala, in muscle cells enhanced the density of GluRIIA, which is a major and calcium-permeable subunit of GluR, at synapses of third instar larval NMJs. ⋯ Notably, another class of GluR containing GluRIIB was enhanced by the postsynaptic expression of T287D. These results suggest that the homeostatic mechanism in T287D larvae works to maintain the level of synaptic responses. Thus, the Drosophila larval NMJs have several regulatory systems to ensure efficient muscle excitability which is necessary for proper larval movement.
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Activation of neurons in the bed nucleus of the stria terminalis (BNST) plays a critical role in stress and anxiety-related behaviors. Previously, we have shown that serotonin (5-HT) can directly modulate BNST neuronal excitability by an action at postsynaptic receptors. In this study we built upon that work to examine the effects of 5-HT on excitatory neurotransmission in an in vitro rat BNST slice preparation. ⋯ Consistent with this observation, sumatriptan decreased the frequency of miniature EPSCs, but had no effect on their amplitude. Taken together, these results suggest that 5-HT suppresses glutamatergic neurotransmission in the BNST by activating presynaptic 5-HT(1B) receptors to decrease glutamate release from presynaptic terminals. This study illustrates a new pathway by which the activity of BNST neurons can be indirectly modulated by 5-HT, and suggests a potential new target for the development of novel treatments for depression and anxiety disorders.
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Stress responses are elicited by a variety of stimuli and are aimed at counteracting direct or perceived threats to the well-being of an organism. In the mammalian central and peripheral nervous systems, specific cell groups constitute signaling circuits that indicate the presence of a stressor and elaborate an adequate response. Pituitary adenylate cyclase-activating polypeptide (PACAP) is expressed in central and peripheral parts of these circuits and has recently been identified as a candidate for regulation of the stress axis. ⋯ Here, abundance of transcripts encoding enzymes required for adrenomedullary catecholamine biosynthesis, namely TH (tyrosine hydroxylase) and PNMT (phenylethanolamine N-methyltransferase), was higher in PACAP+/+ mice after 6 h of unrelieved restraint. Our results suggest that sustained corticosterone secretion, synthesis of the hypophysiotropic hormone CRH in the hypothalamus, and synthesis of the enzymes producing the hormone adrenaline in the adrenal medulla, are controlled by PACAP signaling in the mouse. These findings identify PACAP as a major contributor to the stimulus-secretion-synthesis coupling that supports stress responses in vivo.