Neuroscience
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This chapter presents a brief overview of attachment theory and discusses the importance of the neonatal period in shaping an individual's physiological and behavioural responses to stress later in life, with a focus on the role of the parent-infant relationship, particularly in rodents. In rodents, the role of maternal behaviours goes far beyond nutrition, thermoregulation and excretion, acting as hidden regulators of the pup's physiology and development. In this review, we will discuss the inhibitory role of specific maternal behaviours on the ACTH and corticosterone (CORT) stress response. ⋯ These findings create an opportunity to explore the neurobiological underpinnings of vulnerability and resilience to stress-related disorders. The chapter also provides a brief historical overview and highlights the relevance of attachment theory, and how DEP helps to understand the effects of childhood parental loss as a risk factor for depression, schizophrenia, and PTSD in both childhood and adulthood. Furthermore, we present the concept of environmental enrichment (EE), its effects on stress responses and related behavioural changes and its benefits for rats previously subjected to DEP, along with the clinical implications of DEP and EE.
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Repetitive transcranial magnetic stimulation (rTMS) is a novel non-invasive neuromodulation technique with neuroprotective properties and is used to treat depression. However, the underlying mechanism of action remains unclear. In this study, we examined the possible mechanism mediating the antidepressant effect of rTMS using animal experiments. ⋯ These results indicated that neuron damage occurred in the depression-like rats. After rTMS intervention, the depression-like behavior was alleviated significantly, and the numbers of NSCs and astrocytes, as well as the expression of GFAP and nestin proteins, returned to normal levels. Overall, it is likely that attenuation of NSC proliferation and differentiation into astrocytes produced a neuroprotective effect on hippocampal neurons, which might partly explain the mechanism by which rTMS alleviates depression.
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The glymphatic system is a fluid-clearance pathway that clears cerebral waste products, and its dysfunction has been associated with protein aggregation diseases such as Alzheimer's disease. To understand how the glymphatic system changes with aging, we enrolled 433 cognitive unimpaired participants (236 women and 197 men, 13-88 years) and evaluated the glymphatic function by calculating diffusion tensor imaging analysis along the perivascular space (ALPS) index and explored how the ALPS index is associated with cortical atrophy and cognitive decline in older people. ⋯ Declines in mental manipulation and short-term memory performance in the older participants were associated with a lower ALPS index and cortical atrophy in the amygdala, anterior and posterior cingulate, thalamus and middle frontal regions. Our findings highlight that the ALPS index could be used to evaluate brain reserve and cognitive reserve in older people.
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Postoperative cognitive dysfunction (POCD) is a medically induced, rapidly occurring postoperative disease, which is hard to recover and seriously threatens the quality of life, especially for elderly patients, so it is important to identify the risk factors for POCD and apply early intervention to prevent POCD. As we have known, pain can impair cognition, and many surgery patients experience different preoperative pain, but it is still unknown whether these patients are vulnerable for POCD. Here we found that chronic pain (7 days, but not 1 day acute pain) induced by Complete Freund's Adjuvant (CFA) injected in the hind paw of rats could easily induce spatial cognition and memory impairment after being exposed to sevoflurane anesthesia. ⋯ It was detected the existence of neural projection from ventrolateral PAG (vlPAG) to adjacent nucleus Dorsal Raphe (DR), the origin of serotonergic projection for the whole cerebrum, through virus tracing and patch clamp recordings. The Immunofluorescence staining and western blot results showed that Tryptophan Hydroxylase 2 (TPH2) for serotonin synthesis in the DR was increased significantly in the rats treated with CFA for 7 days and sevoflurane for 3 hours, while chemo-genetic inhibition of the vlPAG-DR projection induced obvious spatial learning and memory impairment. Our study suggests that preoperative chronic pain may facilitate cognitive function impairment after receiving anesthesia through the PAG-DR neural circuit, and preventative analgesia should be a considerable measure to reduce the incidence of POCD.
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Apolipoprotein E (apoE, protein; APOE, gene), divided into three alleles of E2, E3 and E4 in humans, is associated with the progression of white matter lesion load. However, mechanism evidence has not been reported regarding the APOE genotype in early white matter injury (WMI) under subarachnoid hemorrhage (SAH) conditions. In the present study, we investigated the effects of APOE gene polymorphisms, by constructing microglial APOE3 and APOE4-specific overexpression, on WMI and underlying mechanisms of microglia phagocytosis in a mice model of SAH. ⋯ The increased ROS and aggravating mitochondrial damage demonstrated that the damaging effects of APOE4 in SAH may be associated with microglial oxidative stress-dependent mitochondrial damage. Inhibiting mitochondrial oxidative stress by Mitoquinone (mitoQ) can enhance the phagocytic function of microglia. In conclusion, anti-oxidative stress and phagocytosis protection may serve as promising treatments in the management of SAH.