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BACKGROUND@#Microglia plays an indispensable role in the pathological process of sleep deprivation (SD). Here, the potential role of microglial CX3C-chemokine receptor 1 (CX3CR1) in modulating the cognition decline during SD was evaluated in terms of microglial neuroinflammation and synaptic pruning. In this study, we aimed to investigat whether the interference in the microglial function by the CX3CR1 knockout affects the CNS's response to SD.@*METHODS@#Middle-aged wild-type (WT) C57BL/6 and CX3CR1-/- mice were either subjected to SD or allowed normal sleep (S) for 8 h to mimic the pathophysiological changes of middle-aged people after staying up all night. After which, behavioral and histological tests were used to explore their different changes.@*RESULTS@#CX3CR1 deficiency prevented SD-induced cognitive impairments, unlike WT groups. Compared with the CX3CR1-/- S group, the CX3CR1-/- SD mice reported a markedly decreased microglia and cellular oncogene fos density in the dentate gyrus (DG), decreased expression of pro-inflammatory cytokines, and decreased microglial phagocytosis-related factors, whereas increased levels of anti-inflammatory cytokines in the hippocampus and a significant increase in the density of spines of the DG were also noted.@*CONCLUSIONS@#These findings suggest that CX3CR1 deficiency leads to different cerebral behaviors and responses to SD. The inflammation-attenuating activity and the related modification of synaptic pruning are possible mechanism candidates, which indicate CX3CR1 as a candidate therapeutic target for the prevention of the sleep loss-induced cognitive impairments.
Assuntos
Animais , Camundongos , Disfunção Cognitiva , Camundongos Endogâmicos C57BL , Microglia , Doenças Neuroinflamatórias , Privação do SonoRESUMO
Objective:To observe the intrinsic association between cognitive function in patients with Parkinson′s disease (PD) and retinal structural changes in retina nerve fiber layer thickness, macular volume and macular thickness.Methods:A total of 36 patients with PD and 12 normal controls matched with age and sex were selected randomly. Examinations of Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Unified Parkinson′s Disease Rating Scale Ⅲ (UPDRS-Ⅲ), Hoehn-Yahr stage were performed in all subjects. The PD patients were divided into three groups according to the score of MoCA: PD without cognitive impairment (PD-NCI; n=12), PD with mild cognitive dysfunction (PD-MCI; n=13) and PD dementia (PDD; n=11). The retinal nerve fiber layer thickness, macular volume and thickness which were corrected with body mass index (BMI) were determined and analyzed by optical coherence tomography imaging. Results:The total RNFL thickness (μm/BMI) of the PD with cognitive impairment group (PD-MCI group: 3.55±0.12 ( t=2.552, P=0.014), PDD group: 3.07±0.18 ( t=4.122, P=0.000)) was thinner than that of the normal control group (4.05±0.16). The RNFL thickness in each quadrant of the PD with cognitive impairment group (PD-MCI group and PDD group) was thinner than those of the normal control group. The RNFL thickness gradually became thinner with the cognitive impairment increasing ( r=0.558 3, P<0.001). The macular volume (mm 3/BMI) of PD group (PD-NCI group: 0.274±0.010 ( t=2.523, P=0.015), PD-MCI group: 0.268±0.010 ( t=2.848, P=0.007), PDD group: 0.266±0.010 ( t=2.604, P=0.013)) was smaller than that in the normal control group (0.316±0.010), and the macular volume gradually decreased with the severity of cognitive impairment ( r=0.234 1, P=0.024). The macula thickness in each subgroup of PD was thinner than that of the normal control group. The macula thickness gradually became thinner with the cognitive impairment increasing ( r=0.283 9, P<0.001). The macular thickness (normal controls: (10.67±0.12) μm/BMI, PD group: (9.51±0.07) μm/BMI, t=8.312, P<0.001) and volume (normal controls: (0.316±0.010) mm 3/BMI, PD group: (0.270±0.010) mm 3/BMI, t=3.570, P<0.001) became thinner and smaller in patients with PD. Conclusions:In patients with PD, the thickness of the retina nerve fiber layer, the volume and thickness of the macula become thinner/smaller with the severity of cognitive impairments increasing. Macular thickness and volume in patients with PD appear thinner/smaller, which can be used as a valuable biological marker in the early stage of PD. The retina nerve fiber layer thickness in patients with PD becomes thinner, which may be accompanied by cognitive impairment.
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Objective To investigate the effects of hippocampal neurogenesis in spatial learning and memory,especially in spatial long-term memory.Methods Totally 24 wistar rats were randomly divided into two groups:normal control group (NC group,n =12) and irradiation group (IRR group,n =12).We use low-dose irradiation at subgranular zone to inhibit adult hippocampal neurogenesis and new neurons were investigated by 5-Bromo-2-deoxyUridine/neuron specific nuclear protein double-labeling.Four weeks after irradiation,Morris water maze,including navigation test and space exploration assay,was used to detect spatial leaming and memory.Then,in the day 8 and day 15 after the navigation test,space exploration assay was repeated to detect spatial long-term memory.The expression levels of postsynaptic density protein 95 and synaptophysin were evaluated using western blot and real-time quantitative PCR.Results Hippocampal neurogenesis was inhibited by low dose irradiation(2.80 ± 0.44 vs 23.50 ± 1.12,t =20.21,P ＜ 0.01).After the inhibition,the escape latency did not change,while the time spent in target quadrant was significantly declined in the day 2((14.76 ±.2.04) s vs (20.47 ± 1.29) s),day 8((11.95 ± 1.34) s vs (19.52±1.43) s)and day 15((11.79 ±1.35) s vs (21.58 ±1.07) s) after the navigation test (t=2.45,P＜0.05; t =3.76,P＜0.01; t =5.39,P＜0.01).The postsynaptic density protein 95 and synaptophysin expressions were significantly decreased in IRR group.As to the RNA levels,there was also a significant difference between the two groups.Conclusion Hippocampal neurogenesis in the dentate gyrus plays an important role for the formation of spatial long-term memory.