Neuroscience
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Fragile X syndrome (FXS) is the most common heritable cause of intellectual disability and single-gene cause of autism spectrum disorder. The Fmr1 null mouse models much of the human disease including hyperarousal, sensory hypersensitivity, seizure activity, and hippocampus-dependent cognitive impairment. Sleep architecture is disorganized in FXS patients, but has not been examined in Fmr1 knockout (Fmr1-KO) mice. ⋯ Increased low gamma power in CA1 suggests that this hyperactivity was related to increased input to CA1 from CA3. By contrast, slower sharp-wave ripple events (SWRs) in Fmr1-KO mice exhibited longer event duration, slower oscillation frequency, with reduced CA1-PC firing rates during SWRs, yet the incidence rate of SWRs remained intact. These results suggest abnormal neuronal activity in the Fmr1-KO mouse during SWRs, and hyperactivity during other wake and sleep states, with likely adverse consequences for memory processes.
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Alzheimer's disease (AD) is the most common form of dementia that is often accompanied by mood and emotional disturbances and seizures. There is growing body of evidence that neurons expressing γ-aminobutyric acid (GABA) play an important role in regulation of cognition, mood, and emotion as well as seizure susceptibility, but participation of GABAergic neuronal pathology in Alzheimer's disease (AD) is not understood well at present. Here, we report that transgenic mice expressing human amyloid precursor protein Swedish-Dutch-Iowa mutant (APPSweDI) exhibit early loss of neurons expressing GAD67, a GABA-synthesizing enzyme, in advance of the loss of pyramidal neurons in hippocampal CA1 region. ⋯ In the hippocampal CA1 region, GAD67+ neurons expressed high basal levels of neuronal nitric oxide synthase (nNOS) and nitrosative stress (nitrotyrosine). Similarly, GAD67+ neurons in primary cortical and hippocampal neuron cultures also expressed high basal levels of nNOS and degenerated in response to lower Aβ concentrations due to their high basal levels of nitrosative stress. Given the role of GABAergic neurons in cognitive and neuropsychiatric functions, this study reports the role of nNOS-mediated nitrosative stress in dysfunction of GABAergic neurons and its potential participation in early development of cognitive and neuropsychiatric symptoms in AD.
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Wobbler mice are experimental models for amyotrophic lateral sclerosis. As such they show motoneuron degeneration, motor deficits, and astrogliosis and microgliosis of the spinal cord. Additionally, Wobbler mice show increased plasma, spinal cord and brain corticosterone levels and focal adrenocortical hyperplasia, suggesting a pathogenic role for glucocorticoids in this disorder. ⋯ Treatment of Wobbler mice with CORT 113176 reversed the abnormalities of motoneurons and down-regulated proinflammatory mediators and glial reactivity. Expression of glutamate transporters GLT1 and GLAST mRNAs and GLT1 protein was significantly enhanced over untreated Wobblers. In summary, antagonism of GR with CORT 113176 prevented neuropathology and showed anti-inflammatory and anti-glutamatergic effects in the spinal cord of Wobbler mice.
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Selective afferent activation can be used to improve somatosensory function, possibly by altering cortical inhibitory circuit activity. Peripheral electrical stimulation (PES) is widely used to induce selective afferent activation, and its effect may depend on PES intensity. Therefore, we investigated the effects of high- and low-intensity PES applied to the right index finger on tactile discrimination performance and cortical somatosensory-evoked potential paired-pulse depression (SEP-PPD) in 25 neurologically healthy subjects. ⋯ High-intensity PES decreased N20_SEP-PPD in the GOT improvement group but increased N20_SEP-PPD in the GOT decrement group. Furthermore, a greater decrease in GOT discrimination threshold was significantly associated with a greater N20_SEP-PPD decrease in the GOT improvement group. These results suggest that high-intensity PES can improve somatosensory perception in subjects with low baseline function by modulating cortical inhibitory circuits in primary somatosensory cortex.
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Life satisfaction reflects an individual's general evaluation of their overall quality of life. It has been hypothesized that relationship status (i.e. state of intimate relationship such as marriage, unmarried cohabiting, dating with others, single or divorce) may influence individual life satisfaction. However, there is little accessible empirical evidence that allows us to explore this proposition. ⋯ These effects were independent of emotional, instrumental support, and socioeconomic status. Besides, statistical significance of the moderation effect pertaining to relationship status was lost once perceived stress was included as a covariate into the moderation model. Our findings provided empirical evidence for the potentially positive role of relationship status in life satisfaction, and also showed that remission of stress may be a critical factor.