Neuroscience
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Prior work has provided extensive documentation of threshold sensitivity and sensory hair cell losses after noise exposure. It is now clear, however, that cochlear synaptic loss precedes such losses, at least at low-moderate noise doses, silencing affected neurons. To address questions of whether, and how, cochlear synaptopathy and underlying mechanisms change as noise dose is varied, we assessed cochlear physiologic and histologic consequences of a range of exposures varied in duration from 15 min to 8 h and in level from 85 to 112 dB SPL. ⋯ With increasing noise dose, synapse loss grew to ∼50%, then declined for exposures yielding permanent hair cell injury/loss. All synaptopathic, but no non-synaptopathic exposures produced persistent neural response amplitude declines; those additionally yielding permanent OHC injury/loss also produced persistent reductions in OHC-based responses and exaggerated neural amplitude declines. Findings show that widespread cochlear synaptopathy can be present with and without noise-induced sensory cell loss and that differing patterns of cellular injury influence synaptopathic outcomes.
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Drinking alcohol during pregnancy is particularly detrimental for the developing brain and may cause a broad spectrum of cognitive and behavioral impairments, collectively known as fetal alcohol spectrum disorder (FASD). While behavioral abnormalities and brain damage have been widely investigated in animal models of FASD, the sex differences in the vulnerability to perinatal ethanol exposure have received less consideration. Here we investigated the long-term behavioral and molecular effects of acute ethanol-binge like exposure during the early postnatal period (equivalent to the third trimester of human pregnancy) in adult male and female mice. ⋯ Interestingly, only ethanol-exposed adult male mice exhibited memory impairment in the water maze and fear-conditioning tests. Remarkably, hippocampal levels of NMDA-R2B were reduced only in ethanol-exposed male, while total BDNF levels were increased in both male and female ethanol-exposed mice. Our data suggest a different susceptibility of early postnatal ethanol exposure in male and female CD1 mice.
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The amphibian Bv8 and the mammalian prokineticin 1 (PROK1) and 2 (PROK2) are new chemokine-like protein ligands acting on two G protein-coupled receptors, prokineticin receptor 1 (PKR1) and 2 (PKR2), participating to the mediation of diverse physiological and pathological processes. Prokineticins (PKs), specifically activating the prokineticin receptors (PKRs) located in several areas of the central and peripheral nervous system associated with pain, play a fundamental role in nociception. In this paper, to improve the understanding of the prokineticin system in the neurobiology of pain, we investigated the role of PKR2 in pain perception using pkr2 gene-deficient mice. ⋯ This notion was supported by experiments in dorsal root ganglia (DRG) cultures from pkr1 and-pkr2-null mice, demonstrating that the percentage of Bv8-responsive DRG neurons which were also responsive to mustard oil was much higher in PKR1-/- than in PKR2-/- mice. Taken together, these findings suggest a functional interaction between PKR2 and TRP channels in the development of hyperalgesia. Drugs able to directly or indirectly block these targets and/or their interactions may represent potential analgesics.
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Aging is a well-recognized risk factor for sleep disruption. The characteristics of sleep in aging include its disruption by frequent awakenings, a decline in both non-rapid eye movement (nonREM) and REM sleep amounts, and a weaker homeostatic response to sleep loss. Evidence also suggests that sleep in females is more sensitive to changes in the ovarian steroidal milieu. ⋯ We determined sleep-waking features of cycling females across estrus stages. We also compared spontaneous and homeostatic sleep response profiles of young (3-4 months) and old (24-25 months) male and female Fischer-344 rats. The results suggest that: i) sleep-wake architectures across stages of estrus cycle in young females were largely comparable except for a significant suppression of REM sleep at proestrus night and an increase in REM sleep the following day; ii) despite hormonal differences, sleep-wake architecture in male and female rats of corresponding ages were comparable except for the suppression of REM sleep at proestrus night and higher nonREM delta power in recovery sleep; and iii) aging significantly affected sleep-wake amounts, sleep-wake stability, and homeostatic response to sleep loss in both male and female rats and that the adverse effects of aging were largely comparable in both sexes.