Neuroscience
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Comparative Study
Reduction of glycine receptor-mediated miniature inhibitory postsynaptic currents in rat spinal lamina I neurons after peripheral inflammation.
Peripheral inflammation may induce long-lasting sensitization in the central nociceptive system. Neurons in lamina I of the spinal dorsal horn play a pivotal role in the integration and relay of pain-related information. In rats we studied whether changes in passive and active membrane properties and/or alteration of glycine receptor-mediated inhibitory control of spinal lamina I neurons may contribute to central sensitization in a model of peripheral long-lasting inflammation (complete Freund's adjuvant, hindpaw). ⋯ The mean frequency of GlyR-mediated mIPSCs of lamina I neurons ipsilateral to the inflamed hindpaw was, however, significantly reduced by peripheral inflammation when compared with neurons from noninflamed animals. Principal passive and active membrane properties and firing patterns of spinal lamina I neurons were not changed by inflammation. These results indicate that long-lasting peripheral inflammation leads to a reduced glycinergic inhibitory control of spinal lamina I neurons by a presynaptic mechanism.
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Comparative Study
Brainstem prolactin-releasing peptide neurons are sensitive to stress and lactation.
Prolactin-releasing peptide (PrRP) was originally thought to participate in the control of adenohypophyseal prolactin secretion, but its predominant expression in a subset of medullary noradrenergic neurons is more in line with roles in interoceptive and/or somatosensory information processing. To better define functional contexts for this peptide system, immuno- and hybridization histochemical methods were used to monitor the capacity of PrRP neurons to display activational responses to lactation, suckling, acute footshock or hypotensive hemorrhage. PrRP mRNA signal was reduced in the medulla of lactating dams, relative to both male and diestrus female controls, with cell counts revealing 42% and 43% reductions in the number of positively hybridized cells in the nucleus of the solitary tract (NTS) and ventrolateral medulla, respectively. ⋯ A substantially greater fraction of the total medullary PrRP population exhibited sensitivity to footshock than hemorrhage (71 versus 39%, respectively). These results suggest that medullary PrRP neurons are negatively regulated by (presumably hormonal) changes in lactation, and are not recruited to activation by suckling stimuli. These populations exhibit differential sensitivity to distinct acute stressors, and may participate in the modulation of adaptive neuroendocrine and autonomic responses to each.
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Comparative Study
Early microglial activation following neonatal excitotoxic brain damage in mice: a potential target for neuroprotection.
Previous studies in a mouse model of neonatal excitotoxic brain damage mimicking the brain lesions in human cerebral palsy showed microglial activation within 24 h after intracerebral injection of the glutamatergic analog ibotenate. Using this model, we studied the expression of CD-45 antigen, a marker of blood-derived cells, by these activated microglial cells labeled by Griffonia simplicifolia I isolectin B4. ⋯ Repeated i.p. administrations of chloroquine, chloroquine+colchicine, minocycline, or an anti-MAC1 antibody coupled to the toxin saporin before and/or after ibotenate injection induced a significant reduction in the density of isolectin B4-positive cells. This inhibition of resident microglial and/or blood-derived monocytes activation was accompanied by a significant reduction in the severity of ibotenate-induced brain lesions (up to 79% lesion size reduction with the highest minocycline dose) as well as of ibotenate-induced cortical caspase-3 activation (49% reduction).
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Comparative Study
Light microscopic study of GluR1 and calbindin expression in interneurons of neocortical microgyral malformations.
Rat neocortex that has been injured on the first or second postnatal day (P0-1) develops an epileptogenic, aberrantly layered malformation called a microgyrus. To investigate the effects of this developmental plasticity on inhibitory interneurons, we studied a sub-population of GABAergic cells that co-express the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit and the calcium-binding protein, calbindin (CB). Both malformed and control cortex of adult (P40-60) animals contained numerous interneurons double-stained for CB and GluR1. ⋯ This was due to apparent changes in thickness and length of dendrites, rather than to significant changes in the number of interneuronal perikarya in the microgyral cortex. Results indicate that the population of GluR1/CB-containing interneurons is spared in malformed microgyral cortex, but that these cells sustain lasting decreases in their somatic expression of calbindin and alterations of dendritic structure. Potential functional implications of these findings are discussed.
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Hypocretin/orexin modulates sleep-wake state via actions across multiple terminal fields. Within waking, hypocretin may also participate in high-arousal processes, including those associated with stress. The current studies examined the extent to which alterations in neuronal activity, as measured by Fos immunoreactivity, occur within both hypocretin-synthesizing and hypocretin-1 receptor-expressing neurons across varying behavioral state/environmental conditions associated with varying levels of waking and arousal. ⋯ Additionally, these data suggest that waking per se may not be associated with increased hypocretin neurotransmission. In contrast, high-arousal states, including stress, appear to be associated with substantially higher rates of hypocretin neurotransmission. Finally, these studies provide further evidence indicating coordinated actions of hypocretin across a variety of arousal-related basal forebrain and brainstem regions in the behavioral state modulatory actions of this peptide system.