Neuroscience
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Age-related declines in long- and short-term memory show relationships to decreases in N-methyl-d-aspartate (NMDA) receptor expression, which may involve inflammation. This study was designed to determine effects of an anti-inflammatory drug, ibuprofen, on cognitive function and NMDA receptor expression across aging. Male C57BL/6 mice (ages 5, 14, 20, and 26months) were fed ibuprofen (375ppm) in NIH31 diet or diet alone for 6weeks prior to testing. ⋯ Ibuprofen did not alter expression of pro-inflammatory cytokines IL-1β and TNFα, but did reduce the area of reactive astrocyte immunostaining in frontal cortex of aged mice. Enhancement in executive function showed a relationship to increased GluN1-3 mRNA and decreased gliosis. These findings suggest that inflammation may play a role in executive function declines in aged animals, but other effects of ibuprofen on NMDA receptors appeared to be unrelated to aging or inflammation.
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Antidepressant and anxiolytic drugs are widely consumed even by pregnant and lactating women. The metabotropic glutamate receptor 5 (mGlu5) antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) exerts antidepressant- and anxiolytic-like actions. Given that treatment for anxiety and depression use to be prolonged in time, it is conceivable a possible modulation of metabotropic glutamate receptors (mGlu receptors) after prolonged MPEP exposure, which could also modify adenosine A2A receptors (A2AR) since functional cross-talk between them has been reported. ⋯ Neither mGlu receptors nor A2AR were modified in male neonatal brain after maternal MPEP intake. Finally, neither molecular nor behavioral changes (anxiety- and depression-like behavior) were observed in 3-month-old female offspring. In summary, mGlu5 and A2AR are altered in both maternal and female neonatal brain after chronic maternal consumption of MPEP during gestation and/or lactation.
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The high prevalence of chronic pain in posttraumatic stress disorder (PTSD) individuals has been widely reported by clinical studies, which emphasized an urgent need to uncover the underlying mechanisms and identify potential therapeutic targets. Recent studies suggested that targeting activated glia and their pro-inflammatory products may provide a novel and effective therapy for the stress-related pain. In this study, we investigated whether activation of alpha-7 nicotinic acetylcholine receptor (α7 nAChR), a novel anti-inflammatory target, could attenuate PTSD-related chronic pain. ⋯ Further analyses showed that PHA-543613 suppressed SPS-induced spinal glial activation and SPS-elevated spinal pro-inflammatory cytokines, and these were abolished by MLA. Taken together, the present study showed that spinal activation of α7 nAChR by PHA-543613 attenuated mechanical allodynia induced by PTSD-like stress, and the suppression of spinal glial activation may underlie this anti-hyperalgesic effect. Our study demonstrated the therapeutic potential of targeting α7 nAChR in the treatment of PTSD-related chronic pain.
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Egocentric vs. allocentric perspective during observation of hand movements has been related to self-other differentiation such that movements observed from an egocentric viewpoint have been considered as self-related while movements observed from an allocentric viewpoint have been considered as belonging to someone else. Correlational studies have generally found that egocentric perspective induces greater neurophysiological responses and larger behavioral effects compared to an allocentric perspective. However, recent studies question previous findings by reporting greater (μ) suppression and greater transcranial magnetic stimulation (TMS)-induced motor-evoked potentials (MEPs) during observation of allocentric compared to egocentric movements. ⋯ To this aim, we measured the impact of individually adjusted alpha-tuned transcranial alternating current stimulation (tACS) applied over IPL on μ-suppression during hands movement observation from an egocentric and allocentric perspective. Electroencephalography (EEG) was recorded during movement observation before and immediately after tACS. Results demonstrated that tACS decreased μ-reactivity over sensorimotor (but not visual) regions for egocentric (but not allocentric) movement observation providing direct evidence for a causal involvement of IPL in the observation of self- but not other-related hand movement.