Neuroscience
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Prox-1, a prospero-related homeobox gene, is known to be an important transcription factor during embryogenesis. However, very little is known about Prox-1 expression and functions in the adult nervous system. Here we have investigated the expression pattern of Prox-1 mRNA and protein during postnatal brain development and in adult rat and mouse brains using in situ hybridization (ISH), immunohistochemistry (IHC) and Western blotting. ⋯ At PD 14, neither protein variant could be detected. From PD 16 onwards the smaller variant started to predominate and by PD 30 the larger size protein had almost disappeared. The prominent but limited distribution of Prox-1 in the brain suggests its potentially important role during postnatal brain development and in adult CNS, which remains to be ascertained in future studies.
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Prostaglandin E(2) (PGE(2)) is a prototypical inflammatory mediator that excites and sensitizes cell bodies [Kwong K, Lee LY (2002) PGE(2) sensitizes cultured pulmonary vagal sensory neurons to chemical and electrical stimuli. J Appl Physiol 93:1419-1428; Kwong K, Lee LY (2005) Prostaglandin E(2) potentiates a tetrodotoxin (TTX)-resistant sodium current in rat capsaicin-sensitive vagal pulmonary sensory neurons. J Physiol 56:437-450] and peripheral nerve terminals [Ho CY, Gu Q, Hong JL, Lee LY (2000) Prostaglandin E (2) enhances chemical and mechanical sensitivities of pulmonary C fibers in the rat. ⋯ Conversely, evEPSCs of the other eight neurons, which were PGE(2)-responsive, were abolished by 200 nM capsaicin. Furthermore, the PGE(2-)induced depression of evEPSCs was associated with an increase in the paired pulse ratio and a decrease in both the frequency and amplitude of the spontaneous excitatory postsynaptic currents (sEPSCs) and TTX-independent spontaneous miniature excitatory postsynaptic currents (mEPSCs). These results suggest that PGE(2) acts both presynaptically on nerve terminals and postsynaptically on NTS neurons to reduce glutamatergic responses.
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In the present study, the hypothesis that sex-related differences in glutamate-evoked rat masseter muscle afferent discharge may result from estrogen-related modulation of peripheral N-methyl-d-aspartate (NMDA) receptor activity and/or expression was tested by examining afferent fiber discharge in response to masseter injection of NMDA and the expression of NR2A/B subunits by masseter ganglion neurons in male and female rats. The results showed that injection of NMDA into the masseter muscle evoked discharges in putative mechanonociceptive afferent fibers and increased blood pressure that was concentration-dependent, however, a systemic action of NMDA appeared responsible for increased blood pressure. NMDA-evoked afferent discharge was significantly greater in female than in male rats, was positively correlated with plasma estrogen levels in females and was significantly greater in ovariectomized female rats treated with a high dose (5 mug/day) compared with a low dose (0.5 mug/day) of estrogen. ⋯ NMDA-evoked afferent discharge was attenuated by the antagonists ketamine and ifenprodil, which is selective for NR2B containing NMDA receptors. Fewer masseter ganglion neurons expressed the NR2A (16%) subunit as compared with the NR2B subunit (38%), which was expressed at higher frequencies in intact female (46%) and high dose estrogen-treated ovariectomized female (60%) rats than in male (31%) rats. Taken together, these results suggest that sex-related differences in NMDA-evoked masseter afferent discharge are due, at least in part, to an estrogen-mediated increase in expression of peripheral NMDA receptors by masseter ganglion neurons in female rats.
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The delayed and selective vulnerability of post-ischemic hippocampal cornu ammonis (CA) 1 pyramidal neurons correlates with a lack of recovery of normal protein synthesis. Recent evidence implicates sequestration of translational machinery into protein aggregates and stress granules as factors underlying persistent translation arrest in CA1 neurons. However, the relationship between protein aggregates and stress granules during brain reperfusion is unknown. ⋯ At 1 day of reperfusion, ubiquitin-containing aggregates (ubi-protein clusters) occurred in neurons but did not colocalize with stress granules. At 2 days' reperfusion, only in CA1, cytoplasmic protein aggregates colocalized with stress granules, and ubiquitin-containing inclusions accumulated in the nuclei of CA1 pyramidal neurons. Functionally, a convergence of stress granules and protein aggregates would be expected to sustain translation arrest and inhibit clearance of ubiquitinated proteins, both factors expected to contribute to CA1 pyramidal neuron vulnerability.
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Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family involved in plasticity and neuroprotective processes. In recent years, we have reported the presence of BDNF mRNA in the supraoptic nucleus (SON) as well its sensitivity to osmotic stress. The rat SON is a relatively homogenous nucleus mainly consisting of magnocellular soma with their dendritic processes. ⋯ Osmotic stress also increased phosphorylated cAMP response element binding protein immunoreactivity in the SON. In addition, we show in control rats that truncated forms of tyrosine kinase B receptor 2 mRNA represent the most abundant messenger in the SON as compared with brain-derived neurotrophic factor full-length catalytic receptor or truncated forms of tyrosine kinase B receptor 1 mRNA. In conclusion, it is likely that BDNF and their receptors are involved in neuronal plasticity changes induced by osmotic stress in the SON.