Respiratory modulation of sympathetic activity is attenuated in adult rats conditioned with chronic hypobaric hypoxia.

Respiratory modulation of sympathetic nerve activity (SNA) depends on numerous factors including prior experience. In our studies, exposing naïve adult, male Sprague-Dawley rats to acute intermittent hypoxia (AIH) enhanced respiratory-modulation of splanchnic SNA (sSNA); whereas conditioning them to chronic hypobaric hypoxia (CHH) attenuated modulation. Further, AIH can evoke increased SNA in the absence phrenic long-term facilitation.

Respiratory and behavioral dysfunction following loss of the GABAA receptor α4 subunit.

γ-Aminobutyric acid type A (GABAA) receptor plasticity participates in mediating adaptation to environmental change. Previous studies in rats demonstrated that extrasynaptic GABAA receptor subunits and receptors in the pons, a brainstem region involved in respiratory control, are upregulated by exposure to sustained hypobaric hypoxia. In these animals, expression of the mRNA encoding the extrasynaptic α4 subunit rose after 3 days in sustained hypoxia, while those encoding the α6 and δ subunits increased dramatically by 2 weeks.

Hu proteins regulate alternative splicing by inducing localized histone hyperacetylation in an RNA-dependent manner.

Recent studies have provided strong evidence for a regulatory link among chromatin structure, histone modification, and splicing regulation. However, it is largely unknown how local histone modification patterns surrounding alternative exons are connected to differential alternative splicing outcomes. Here we show that splicing regulator Hu proteins can induce local histone hyperacetylation by association with their target sequences on the pre-mRNA surrounding alternative exons of two different genes.

Sulfasalazine blocks the development of tactile allodynia in diabetic rats.

Objective: Diabetic neuropathy is manifested either by loss of nociception (painless syndrome) or by mechanical hyperalgesia and tactile allodynia (pain in response to nonpainful stimuli). While therapies with vasodilators or neurotrophins reverse some functional and metabolic abnormalities in diabetic nerves, they only partially ameliorate neuropathic pain. The reported link between nociception and targets of the anti-inflammatory drug sulfasalazine prompted us to investigate its effect on neuropathic pain in diabetes.

Adaptation to hypobaric hypoxia involves GABA A receptors in the pons.

Survival in low-oxygen environments requires adaptation of sympathorespiratory control networks located in the brain stem. The molecular mechanisms underlying adaptation are unclear. In naïve animals, acute hypoxia evokes increases in phrenic (respiratory) and splanchnic (sympathetic) nerve activities that persist after repeated challenges (long-term facilitation, LTF).

Association of PSD-95 with ErbB4 facilitates neuregulin signaling in cerebellar granule neurons in culture.

The growth factor neuregulin 1 (NRG) selectively induces an increase in the gamma-aminobutyric acid (GABA)(A) receptor beta2 subunit protein in rat cerebellar granule neurons in culture. We previously demonstrated that NRG acts by triggering ErbB4 receptor phosphorylation and subsequent signaling through the mitogen-activated kinase (MAPK), phosphatidyl inositol-3 kinase (PI-3K) and cyclin-dependent kinase 5 (cdk5) pathways. In this report we show that the scaffolding protein, PSD-95, plays a key role in mediating the effects of NRG and that reducing its level attenuates the NRG-induced increase in beta2 subunit expression.

The serotonin type 3A receptor facilitates luteinizing hormone release and LHbeta promoter activity in immortalized pituitary gonadotropes.

The 5-hydroxytryptamine type 3A receptor (5-HT3AR) is a ligand-gated cation channel activated by serotonin. This receptor is expressed throughout the nervous system as well as in the pituitary gland. Although it has been documented that the 5-HT3AR modulates exocytosis in neurons, its role in the pituitary gland has not been determined.

Pontine GABAergic pathways: role and plasticity in the hypoxic ventilatory response.

The hypoxic ventilatory response (HVR) was compared before and after uni- and bi-lateral injections of bicuculline, a GABA(A) receptor antagonist, into the ventrolateral (vl) pons and before and after conditioning animals to chronic sustained hypoxia (CSH). The HVR was assessed by recording phrenic nerve activity (PNA) during and after brief exposures to hypoxia (8% O(2) and 92% N(2) for 45s). Inspiratory (T(I)) and expiratory (T(E)) durations were averaged before hypoxia, at the peak breathing frequency during hypoxia, before the end of hypoxia, immediately after hypoxia, and 60s after hypoxia.

Neuregulin induces GABAA receptor beta2 subunit expression in cultured rat cerebellar granule neurons by activating multiple signaling pathways.

The GABAA receptor beta subunit is required to confer sensitivity to gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the CNS. In previous studies we demonstrated that the growth and differentiation factor neuregulin 1 (NRG1) selectively induced expression of the beta2 subunit mRNA and encoded protein in rat cerebellar granule neurons in culture. In the present report we examine the signaling pathways that mediate this effect.

Three putative N-glycosylation sites within the murine 5-HT3A receptor sequence affect plasma membrane targeting, ligand binding, and calcium influx in heterologous mammalian cells.

The serotonin type 3(A) receptor (5-HT3(A)R) is a ligand-gated ion channel (LGIC) that modulates a diverse set of cognitive and physiological functions. The 5-HT3(A)R, as with other LGICs, is a pentameric ion channel comprising five glycoprotein subunits. Although the N-terminal of the 5-HT3(A)R contains three putative N-linked glycosylation sites, the importance of each glycosylation site has not yet been established.

Signaling by bone morphogenetic proteins and Smad1 modulates the postnatal differentiation of cerebellar cells.

Previous studies have demonstrated that bone morphogenetic proteins (BMPs) activate the Smad1 signaling pathway to regulate cell determination and differentiation in the embryonic nervous system. Studies examining gene and protein expression in the rat cerebellum suggest that this pathway also regulates postnatal differentiation. Using microarrays, we found that Smad1 mRNA expression in the cerebellum increases transiently at postnatal day 6 (P6).