Neuroscience
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Toll-like receptor-4 (TLR4), a member of the TLR family, plays a key role in inflammation-related diseases of the nervous system. TLR4 knockout mice are widely used in various neurological disease studies, and there is a clear correlation between inflammation and behavior. Therefore, elucidating the effect of TLR4 on neurobehavioral function is essential, and the related mechanisms need to be explored. ⋯ TLR4 knockout significantly attenuated the fear response in 16-m-old mice. The TLR4-/- mice also had better blood-brain barrier integrity, increased expression of tight junction-associated proteins, increased cerebral cortical blood flow and reduced proinflammatory cytokine expression in the cortex and cerebrospinal fluid. Our results suggest that TLR4 deletion ameliorates significant neurobehavioral dysfunction during the aging stage, as well as multiple abnormalities in brain function and structure due to alterations in tight junction-associated proteins and inflammatory factors.
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Silent myocardial infarction (MI) is critical for clinical practice with increasing risk for women and the cause remains a medical mystery. Upon the discovery of female-specific Ah-type baroreceptor neurons (BRNs), we hypothesize that glutamate mediates depressor response through afferent-specific expression of particular glutamate receptors (mGluRs) leading descending inhibition of cardiac nociception. In vivo, tail-flick reflex and electromyography were assessed to evaluate glutamate-mediated blood pressure regulation, peripheral and cardiac nociception. ⋯ Glutamate in serum, NG and nucleus tractus solitary (NTS) was raised significantly in the model rats of both sexes vs. sham-controls. Female-specific expression of mGluR7 in the baroreflex afferent pathway, especially higher expression in Ah-type BRNs, contributes significantly to cardiac analgesia, which may explain that the pathogenesis of silent MI occurs mainly in female patients. Therefore, higher expression of mGluR7 in female-specific subpopulation of Ah-type BRNs plays a critical role in cardiac analgesia and peripheral nociception.
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When processing repeated stimuli, the neural response is attenuated (i.e., neural adaptation) and performance seems to be facilitated; however, this neural adaptation negatively influences the subsequent processing of novel stimuli. The present study was designed to test whether and how temporal expectations reduce neural adaptation and attenuate the negative influence of neural adaptation on subsequent novel problem solving. Temporal expectations were experimentally manipulated by asking participants to solve a novel problem following three to five repeated problems, generating the expectation of repeated events in the first three serial positions as well as that of novel events in the fourth to sixth serial positions. ⋯ Regarding the novel events, the conflict monitoring- and resolution-related N400, P600 and LNC amplitudes decreased with decreased neural adaptation. These results indicate that the expectation of novel events attenuate the negative influence of neural adaptation on the subsequent processing of novel events. This study provides new insight into alleviating the constraints imposed by frequently used knowledge on the processing of novel stimuli.
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Traumatic brain injury (TBI) is a leading cause of disability and death in adolescents, and there is a lack of effective methods of treatment. The neuroprotective effects exerted by TGF-β1 can ameliorate a range of neuronal lesions in multiple central nervous system diseases. In this study, we used an in-vitro TBI model of mechanical injury on murine primary cortical neurons and the neuro-2a cell line to investigate the neuroprotective role played by TGF-β1 in cortical neurons in TBI. ⋯ TGF-β1 significantly upregulated the expression of Cav1.2 by activating the p38 MAPK pathway and by inhibiting trauma-induced neuronal apoptosis. In conclusion, TGF-β1 increased trauma-injured murine cortical neuronal activity and inhibited apoptosis by upregulating Cav1.2 channels via activating the p38 MAPK pathway. Therefore, the TGF-β1/p38 MAPK/Cav 1.2 pathway has the potential to be used as a novel therapeutic target for TBI.