Neuroscience
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Prolactin (PRL) has many functions in the CNS, including neuroprotection. During lactation, the dorsal hippocampus is protected from excitotoxic kainic acid (KA)-induced cellular damage. We have previously reported that systemic pre-treatment with ovine PRL had similar protective effects in female rats. ⋯ Treatment with either hPRL or S179D-PRL or the combination prevented the damaging effect of KA in these hippocampal regions (∼95% of corresponding control), but was not completely effective at preventing early seizure-related behaviors such as staring and wet dog shakes. Analysis of signals generated by hPRL and S179D-PRL showed no activation of signal transducer and activation of transcription 5 (Stat5) or other signaling molecules in the hippocampus, but activation of extracellular-regulated kinase (ERK)1/2 in the amygdala. These results support a central protective effect of both PRL forms and suggest that PRL could be exerting its protective action by indirectly modulating input signals to the hippocampus and thus regulating excitability.
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Endometriosis pain is a very common and extremely disabling condition whose mechanism is still poorly understood. While increased levels of leptin have been reported in patients with endometriosis, their contribution to endometriosis pain has not been explored. Using a rodent model of endometriosis we provide evidence for an estrogen-dependent contribution of leptin in endometriosis-induced pain. ⋯ Taken together these data support the hypothesis that leptin, generated in ectopic endometrial lesions produces mechanical hyperalgesia by acting on nociceptors innervating the lesion. This sensitivity to leptin is dependent on estrogen levels. Thus, interventions targeting leptin signaling, especially in combination with interventions that lower estrogen levels, might be useful for the treatment of endometriosis pain.
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Human modalities play a vital role in the way the brain produces mental representations of the world around us. Although congenital blindness limits the understanding of the environment in some aspects, blind individuals may have other superior capabilities from long-term experience and neural plasticity. This study investigated the effects of congenital blindness on temporal and spectral neural encoding of speech at the subcortical level. ⋯ Results indicate that congenitally blind subjects have improved hearing function in response to the /da/ syllable in both source and filter classes of sABR. It is possible that these subjects have enhanced neural representation of vocal cord vibrations and improved neural synchronization in temporal encoding of the onset and offset parts of speech stimuli at the brainstem level. This may result from the compensatory mechanism of neural reorganization in blind subjects influenced from top-down corticofugal connections with the auditory cortex.
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Previous research has demonstrated that diabetes induces learning and memory deficits. However, the mechanism of memory impairment induced by diabetes is poorly understood. Dietary fatty acids, especially polyunsaturated fatty acids, have been shown to enhance learning and memory and prevent memory deficits in various experimental conditions. ⋯ STZ-induced diabetes impaired spatial learning and memory of rats, which was associated with the inflammation, oxidative stress and apoptosis of hippocampal neurons. Fish oil administration ameliorated cognitive deficit, reduced oxidative stress and tumor necrosis factor α (TNF-α), protected the hippocampal neurons by increasing Protein Kinase B (AKT) phosphorylation and decreasing caspase-9 expression. These results suggested that the principle mechanisms involved in the antidiabetic and neuroprotective effect of fish oil were its antioxidant, anti-inflammatory and anti-apoptosis potential, supporting a potential role for fish oil as an adjuvant therapy for the prevention and treatment of diabetic complications.
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Neuromedin U (NMU) is a highly conserved neuropeptide which regulates food intake and body weight. Transgenic mice lacking NMU are hyperphagic and obese, making NMU a novel target for understanding and treating obesity. Neuromedin U receptor 2 (NMUR2) is a high-affinity receptor for NMU found in discrete regions of the central nervous system, in particular the paraventricular nucleus of the hypothalamus (PVN), where it may be responsible for mediating the anorectic effects of NMU. ⋯ However, when the same rats were fed a high-fat diet (45% fat), they consumed significantly more food, gained more body weight, and had increased feed efficiency relative to controls. Furthermore, NMUR2 knockdown rats demonstrated significantly greater binge-type food consumption of the high-fat diet and showed a greater preference for higher-fat food. These results demonstrate that NMUR2 signaling in the PVN regulates consumption and preference for high-fat foods without disrupting feeding behavior associated with non-obesogenic standard chow.