Neuroscience
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ATP-sensitive potassium (K(ATP)) channels may be linked to mechanisms of pain after nerve injury, but remain under-investigated in primary afferents so far. We therefore characterized these channels in dorsal root ganglion (DRG) neurons, and tested whether they contribute to hyperalgesia after spinal nerve ligation (SNL). We compared K(ATP) channel properties between DRG somata classified by diameter into small or large, and by injury status into neurons from rats that either did or did not become hyperalgesic after SNL, or neurons from control animals. ⋯ These findings indicate that functional K(ATP) channels are present in normal DRG neurons, wherein they regulate RMP. Alterations of these channels may be involved in the pathogenesis of neuropathic pain following peripheral nerve injury. Their biophysical and pharmacological properties are preserved even after axotomy, suggesting that K(ATP) channels in primary afferents remain available for therapeutic targeting against established neuropathic pain.
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The majority of the studies on the actions of estrogens in the ventrolateral part of the hypothalamic ventromedial nucleus (VMNvl) concern the factors that modulate the receptive component of the feminine sexual behavior and the expression of molecular markers of neuronal activation. To further our understanding of the factors that regulate synaptic plasticity in the female VMNvl, we have examined the effects of estradiol and progesterone, and of estrogen receptor (ER) subtype selective ligands on the number of dendritic and spine synapses established by individual VMNvl neurons and on sexual behavior. In contrast to earlier studies that analyzed synapse densities, our results show that exogenous estradiol increases the number of spine as well as of dendritic synapses, irrespective of the dose and regimen of administration. ⋯ Despite its relevant role in feminine sexual behavior, progesterone had no synaptogenic effect in the VMNvl as no changes in synapse numbers were noticed in rats treated with progesterone alone, with estradiol followed by progesterone or with the antiprogestin mifepristone (RU486). Except for the sequential administration of estradiol and progesterone, none of the regimens was associated with lordosis response to vaginocervical stimulation. Therefore, from the sex steroids that undergo cyclic variations over the estrous cycle, only estrogens, acting through both ERalpha and ERbeta, play a key role in the activation of the neural circuits involving the ventromedial nucleus of the hypothalamus.
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Neuroglobin (Ngb) is a tissue globin specifically expressed in neurons. Our laboratory and others have shown that Ngb overexpression protects neurons against hypoxia/ischemia, but the underlying mechanisms remain poorly understood. Recent studies demonstrate that hypoxia/ischemia induces a multitude of spatially and temporally regulated responses in gene expression, and initial evidence suggested that Ngb might function in altering biological processes of gene expression. ⋯ Additionally, three genes that initially showed no changes in WT neurons (Ctgf, Egfr and Pea15) were downregulated after OGD in the Ngb-Tg neurons. These findings suggest that Ngb overexpression modulates mRNA expression of multiple hypoxic response genes in the early phase after OGD/reoxygenation. Further studies on these gene networks and interactions may lead to better understanding of Ngb in signaling pathways that contribute to neuroprotection.
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Na(+),K(+)-ATPase contributes to the asymmetrical distribution of sodium and potassium ions across the plasma membrane and to maintenance of the membrane potential in many types of cells. Alterations in this protein may play a significant role in many human neurological disorders, including epilepsy. We studied expression of the alpha3 isoform of Na(+),K(+)-ATPase in the freeze lesion (FL) microgyrus model of developmental epileptogenesis to test the hypothesis that it is downregulated following neonatal cortical injury. ⋯ A reduction in alpha3 mRNA was observed in the neuropil of FL cortical layer V up to 1610 mum from the microgyral edge. The developmental time course for expression of the alpha3 subunit between P7 and P60 was examined in naive rat cortices and results showed that there was a significant increase in alpha3 IR between P7 and P10. The significant decreases in Na(+),K(+)-ATPase in the paramicrogyral cortex may contribute to epileptogenesis.
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The GABA(B) receptor (GABA(B)R) agonist baclofen is known to have a beneficial potency in patients who suffer from dystonia, a neurological syndrome characterized by involuntary co-contractions of opposing muscles. The underlying mechanisms of this movement disorder are still unclear. Previous studies in the dt(sz) hamster, an animal model of primary paroxysmal dystonia, revealed alterations of the GABAergic system, including a reduction of striatal GABAergic interneurons and an altered GABA(A) receptor (GABA(A)R) binding in several brain regions. ⋯ Single striatal administration of the selective GABA(B)R antagonist CGP 35348 [(3-Aminopropyl)(diethoxymethyl)phosphinic acid, 5 and 10 microg/0.5 microl] did not influence the severity of dystonia, but antagonized the antidystonic effect of baclofen. For receptor autoradiographic studies, [H3]-CGP 54626 ([S-(R*,R*)]-[3-[[1-(3,4-Dichlorophenyl)ethyl]amino]-2-hydroxypropyl](cyclohexylmethyl)phosphinic acid) binding was determined in dt(sz) hamsters in comparison to non-dystonic control hamsters. [H3]-CGP 54626 binding was not altered in motor areas but in some limbic structures of dt(sz) hamsters. In view of the absence of striatal changes in GABA(B) binding, the strong antidystonic effect of baclofen after its striatal microinjection is probably related to a suppression of a pathophysiologically increased synaptic activity.