Neuroscience
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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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A multicenter randomized clinical trial demonstrated that acute ischemic stroke patients treated with edaravone, a scavenger of hydroxyl radicals, had significant functional improvement. We tested the hypothesis that edaravone has protective effects against white matter lesions (WML) and endothelial injury, using a rat chronic hypoperfusion model. Adult Wistar rats underwent ligation of bilateral common carotid artery (LBCCA) and were divided into the edaravone group (injected once only immediately after LBCCA [n=39, ED(1)]; and injected on three consecutive days [n=39, ED(3)]), the vehicle group (n=39), and the sham group (n=15). ⋯ These results were more evident in the ED(3) group. Moreover, at day 21 after LBCCA, spatial memory but not motor function, and axonal damage were significantly improved by three-time treatment of edaravone (P<0.05). Our results indicated that 3-day treatment with edaravone provides protection against WML through endothelial protection and free radical scavenging and suggested that edaravone is potentially useful for the treatment of cognitive impairment.
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Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are active at resting membrane potential and thus contribute to neuronal excitability. Their increased activity has recently been demonstrated in models of nerve injury-induced pain. The major aim of the current study was to investigate altered HCN channel protein expression in trigeminal sensory neurons following inflammation of the dura. ⋯ In addition, the number of retrogradely labeled neurons from the dura expressing HCN1 and HCN2 was significantly increased to 247% (HCN1) and 171% (HCN2), three days after inflammation. When the opioid receptor partial agonist, buprenorphine, was given systemically, immediately after CFA, the inflammation-induced increase in HCN protein expression in both Western blot and immunohistochemical experiments was not observed. These results suggest that HCN1 and HCN2 are involved in inflammation-induced sensory neuron hyperexcitability, and indicate that an opioid receptor agonist can reverse the protein upregulation.
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Individuals vary in the way in which they cope with stressful situations. It has been suggested that 'active' coping behaviour, characterised by aggression and territorial control, is more effective in moderating the stress associated with social defeat than 'passive' coping behaviour, as characterised by immobility, decreased reactivity, and low aggression. We used the rodent 'resident/intruder' paradigm to determine whether individual differences in coping behaviour modulate the acute adrenocortical response to social defeat. ⋯ The results of this analysis indicated that 'low fight' and 'low guard' intruders, i.e. those that achieved a fight or a guard score below the 20th percentile, had significantly higher numbers of Fos-positive neurons in forebrain regions such as the medial prefrontal cortex and the amygdala than did control animals exposed to an empty resident's cage. In summary, the present data suggest that 'active' coping behaviour is associated with both a smaller adrenocortical response and a lower level of 'neural activation' following social defeat. This outcome differs from that of earlier studies, a difference that we suggest is due to the fact that the present study is the first to assess coping on the basis of behaviour actually displayed during the conflict interaction.
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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.