Behavioural brain research
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Increasingly, it is being recognised that traumatic brain injury (TBI) is not just an acute event but instead results in ongoing neuronal injury that may lead to chronic impairments in multiple cognitive domains. Of these, deficits in executive function are one of the more common changes reported following TBI, and are a major predictor of well-being, social function and quality of life in individuals with a history of TBI. In order to fully understand the relationship between TBI and executive dysfunction, including brain mechanisms that may account for this, experimental models are clearly needed. ⋯ Interestingly, there were no differences in learning, motivation, attention, response time or impulsivity at 1 month, 6 months or 12 months post-injury in any of the TBI groups compared to sham, regardless of the initial severity of the injury. Instead, most of the effects on executive function seen at the 12 month timepoint appeared to be a result of ageing, not injury. As even the 12-month timepoint represents middle age in the rat, future studies will be needed to further probe these effects, in order to determine whether DAI may influence the presentation of executive dysfunction in older age.
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Neuropeptide S (NPS) has shown anxiolytic-like effects in rodents after acute administration, but its long-term effects remain unknown. Gene therapy enables the targeted delivery of DNA to cell nuclei, and recombinant adeno-associated viral (rAAV) vectors have been identified as suitable tools for stable overexpression. Thus, to explore the effects of long-term expression of NPS, the present study examined anxiety- and depressive-like effects after rAAV-mediated NPS overexpression in the rat amygdala. ⋯ Immunohistochemical stainings revealed NPS-positive cells in the central and basolateral region of the amygdala in rAAV-NPS but not rAAV-Empty rats, indicating successful transduction. Our study provides novel evidence for sustained anxiolytic-like properties of NPS by transgenic overexpression. These data suggest that rAAV-NPS application deserves further attention as a potential treatment strategy for anxiety in humans.
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Neuroinflammation is often associated with the development of major depressive disorder (MDD)-related symptoms. Previous studies have indicated that activation of glial cells, upregulation of proinflammatory cytokines and dysregulation of adrenergic system in the central nervous system (CNS) could be the key mediators to modulate depression-related behaviors after peripheral immune activation. Central α7 nicotinic acetylcholine receptor (α7 nAChR) has a role in the regulation of the cholinergic anti-inflammatory pathway. ⋯ Following LPS treatment, PNU120596 hindered activation markers of the microglia and astrocytes (cluster of differentiation molecule 11b and glial fibrillary acidic protein) and upregulation of proinflammatory cytokines such as interleukin 1 beta and tumor necrosis factor-alpha in the hippocampus and prefrontal cortex. NE level that was reduced by peripheral LPS challenge was normalized by PNU120596 effects in both brain regions. Overall, the results in this study indicate that activation of α7 nAChR by PAM effectively prevents LPS-induced anxiety, cognitive deficit, and depression-like behaviors and regulates relevant neuroinflammatory markers in the hippocampus and prefrontal cortex.
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Traumatic brain injury (TBI) is a common risk factor for later neurodegeneration, which can manifest as dementia. Despite this, little is known about the time-course of development of functional deficits, particularly cognitive and neuropsychiatric impairments, and whether these differ depending on the nature of the initiating insult. Therefore, this study investigated long term functional impairment at 12 months post-injury following diffuse TBI of different severities. ⋯ Neither repetitive mild TBI nor single mild TBI animals showed significant functional impairments when compared to shams. Thus, this study provides the first insight into chronic functional impairments associated with different severities of diffuse TBI, with moderate to severe TBI being a higher risk factor for impaired cognitive function at 12 months post-injury. Taken together, this may have implications for risk of dementia development following different severities of injury.
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Sleep disturbance can result in memory impairment, and both sleep and hippocampal memory formation are maintained by circadian clock genes. Although preoperative sleep deprivation is known to be an independent risk factor for postoperative cognitive dysfunction (POCD) after inhalation anesthesia, the circadian mechanisms involved are currently unclear. To examine this issue, we constructed models of rapid eye movement sleep deprivation (RSD) and POCD after sevoflurane inhalation, to evaluate the circadian mechanisms underlying preoperative sleep deprivation-induced POCD after sevoflurane inhalation. ⋯ In addition, sevoflurane inhalation activated the plasma expression of S100β and IL-6, particularly after sleep deprivation. Sleep deprivation aggravated pathogenic impairment of pyramidal neurons and activated astrocytes in CA1 after sevoflurane inhalation. These results suggest that preoperative RSD aggravates hippocampal memory impairment by enhancing neuroinflammatory injuries after sevoflurane inhalation, which is related to hippocampal clock gene abnormalities.