Neuroscience
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Aging is associated with sleep-wake disruption, dampening of circadian amplitudes, and a reduced homeostatic sleep response. Aging is also associated with a decline in hypothalamic cell proliferation. We hypothesized that the aging-related decline in cell-proliferation contributes to the dysfunction of preoptic-hypothalamic sleep-wake and circadian systems and consequent sleep-wake disruption. ⋯ AraC-treated mice also exhibited lower delta activity within nonREM recovery sleep. The sleep-wake architecture of AraC-treated mice was similar to that observed in aged mice. These findings are consistent with a hypothesis that a decrease in hypothalamic cell proliferation/neurogenesis is detrimental to sleep-wake and circadian systems and may underlie sleep-wake disturbance in aging.
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Aging is often considered to affect both the peripheral (i.e. the cochlea) and central (brainstem and thalamus-cortex) auditory systems. We investigated the effects of aging on the cochlea, brainstem and cortex of female Sprague-Dawley rats. The auditory nerve threshold remained stable between the ages of nine and 21 months, as did distortion product otoacoustic emissions and the number of ribbon synapses between inner hair cells and nerve fibers. ⋯ Behavioral performance for the modulation depth of amplitude modulation noise was worse in 21-month old animals than in other animals. Age-related alterations of cortical and behavioral responses were thus observed in animals displaying no signs of aging at the peripheral level. These results suggest that intrinsic, central aging effects can affect the perception of acoustic stimuli independently of the effects of aging on peripheral receptors.
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Directing differentiation of neural stem/progenitor cells (NSCs/NPCs) to produce functional neurons is one of the greatest challenges in regenerative medicine. Our previous paper has confirmed that electrical stimulation has a high efficiency of triggering neuronal differentiation by using isolated filum terminale (FT)-derived NPCs. To further clarify the intrinsic molecular mechanisms, protein-protein interaction (PPI) network analysis was applied to pinpoints novel hubs in electric field (EF)-induced neuronal differentiation. ⋯ The data showed that the expression level of Ascl1 was enhanced by electrical stimulation and positively correlated to EF strength. Moreover, we identified that the expression of Ascl1 positively regulated neuronal differentiation of NPCs and can be up-regulated by EF-stimulation through the activation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway. Therefore, this study provides new insights into the role of Ascl1 and its relevant PI3K/Akt pathway in regulating of EF-induced neuronal differentiation and pointed out that continuous expression of Ascl1 in NPCs is required for EF-induced neuronal differentiation.
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Bidirectional selection of mice for high (HA) and low (LA) swim stress-induced analgesia (SSIA) is associated with a divergent response to opioids. In the current study, we investigated whether the genetic divergence in opioid system activity between HA and LA mice also affects cannabinoid sensitivity. Additionally, we also investigated whether the endocannabinoid system mediates SSIA in these lines. ⋯ The intensity of behavioral responses to WIN55,212-2 was correlated with increased G-protein activation in the periaqueductal gray matter, frontal cortex, striatum and thalamus in HA mice. A weak response to WIN55,212-2 in LA mice could depend on impaired CB2 receptor signaling. In conclusion, differences in both opioid and cannabinoid sensitivity between HA and LA mice could stem from alterations in intracellular second messenger mechanisms involving G-protein activation.
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In the cortex, demarcated unimodal sensory regions often respond to unforeseen sensory stimuli and exhibit plasticity. The goal of the current investigation was to test evoked responses of primary visual cortex (V1) neurons when an adapting auditory stimulus is applied in isolation. ⋯ Our results suggest that neurons specific to either layer dynamically integrate features of sound and modify the organization of the orientation map of V1. Intriguingly, these experiments present novel findings that the mere presentation of a prolonged auditory stimulus may drastically recalibrate the tuning properties of the visual neurons and highlight the phenomenal neuroplasticity of V1 neurons.