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Sleep deprivation and insulin resistance (IR) are two risk factors for Alzheimer's disease. As the population of people with IR increases and sleep restriction (SR) due to staying up late becomes the "new normal", it is necessary to investigate the effects and molecular pathogenesis of chronic SR on cognitive function in insulin resistance. In this study, 4-week-old mice were fed a high-fat diet (HFD) for 8 weeks to establish IR model, and then the mice were subjected to SR for 21 days, and related indicators were assessed, including cognitive capacity, apoptosis, oxidative stress, glial cell activation, inflammation, blood-brain barrier (BBB) permeability and adiponectin levels, for exploring the potential regulatory mechanisms. Compared with control group, IR mice showed impaired cognitive capacity, meanwhile, SR not only promoted Bax/Bcl2-induced hippocampal neuronal cell apoptosis and Nrf2/HO1- induced oxidative stress, but also increased microglia activation and inflammatory factor levels and BBB permeability, thus aggravating the cognitive impairment in IR mice. Consequently, changing bad living habits and ensuring sufficient sleep are important intervention strategies to moderate the aggravation of IR-induced cognitive impairment. [Display omitted] • Sleep restriction (SR) induces neuronal apoptosis, oxidative stress and inflammation leading to cognitive impairment. • SR increased blood-brain barrier permeability while decreasing adiponectin levels. • SR caused further exacerbation of the above changes in insulin-resistant mice. • Poor lifestyle (SR) exacerbates neurologic complications associated with insulin resistance. [ABSTRACT FROM AUTHOR]

Vascular dementia (VD) is the second most common cause of dementia after Alzheimer's disease. Neuroinflammation contributes to pathogenesis of VD. Neurotropin (NTP) is an analgesic that has been shown to suppress inflammation and neural repair. But its effects on VD are still unclear. Therefore, this study aimed to investigate the therapeutic effects and potential mechanisms of NTP in the VD model mice established by bilateral common carotid artery stenosis method. In VD mice, we found that NTP treatment increased cerebral blood flow by Laser speckle imaging, reduced neuron loss by Nissl, HE and immunochemistry staining, attenuated white matter damage by magnetic resonance imaging and ultrastructural damage by transmission electron microscope, improved cognitive functions by new object recognition test and three-chamber test, Y maze test and Morris water maze test, inhibited significantly glial activation by immunofluorescence methods, reduced the expression of TLR4, down-regulated expression of MyD88 and phosphorylation of NF-κB P65, decreased the levels of pro-inflammatory cytokines IL-1β, IL-6 and TNFα. Further, we showed that administration of a TLR4 inhibitor TAK242 had a similar effect to NTP, while the TLR4 agonist CRX-527 attenuated the effect of NTP in the VD mice. Collectively, our study suggested that NTP alleviates cognitive impairment by inhibiting TLR4/MyD88/NF-κB inflammation signaling pathway in the VD mice. Thus, NTP may be a promising therapeutic approach and a potential TLR4 inhibitor for VD. [Display omitted] • VD mice showed neuronal loss and glial activation. • NTP ameliorated cognitive impairment in VD mice, decreased white matter degeneration and reduced levels of pro-inflammatory cytokines. • TAK242 had a similar effect to NTP, while CRX-527 attenuated the effects of NTP in VD mice. [ABSTRACT FROM AUTHOR]

Objective: It was recently found that structural changes in the substantia nigra (SN) and motor symptoms become more prominent in Parkinson's disease (PD) patients with striatal silent lacunar infarction (SSLI) than in those without SSLI. Hyperhomocysteinemia (HHCY) was an independent risk factor for SSLI in PD patients. In this follow-up study, we investigated the relationship between HHCY and structural changes of the SN in PD patients.Methods: A total of 72 untreated early PD patients without SSLI, divided into control and HHCY groups, were enrolled in this study. All participants underwent conventional MRI and diffusion kurtosis imaging (DKI) twice; at baseline and at the 2-year visit. The differences of the following variables between the two groups were analyzed: mean kurtosis (MK) values of the SN, the severity of disease, daily dosage of levodopa, and the variation of these indexes from baseline to 2-year visit. Logistic regression analysis was used to identify the relationship between HHCY and structural changes of the SN in PD patients.Results: 1.All variables mentioned above showed significant differences between the two groups. 2. The variation in MK values of the SN were positively correlated with the variation in the severity of disease. 3. HHCY was an independent risk factor for the variation in MK values of the SN in PD patients.Conclusion: HHCY is associated with the structural changes of the SN in PD patients. As PD progresses, motor symptoms become aggravated with increased structural changes to the SN, especially in patients with HHCY. [ABSTRACT FROM AUTHOR]

Objective: Striatal silent lacunar infarction (SSLI) is associated with structural changes to the substantia nigra (SN), detectable by diffusion kurtosis imaging (DKI). In this follow-up study, we investigated the effects of SSLI on the SN and movement disorders in patients with Parkinson's disease (PD).Methods: A total of 60 untreated patients with early-stage PD, divided into control and SSLI groups, were enrolled in this study. All participants underwent conventional MRI and DKI twice; at baseline and after a 1-year period. We analyzed the differences of the following variables between the two groups: mean kurtosis (MK) values of the SN, the severity of disease, daily dosage of levodopa, and the variation of these indexes from baseline to 1-year visit. Logistic regression analysis was used to identify the major risk factors for SSLI in PD patients.Results: 1. All variables showed significant differences between the two groups. 2. The variation in MK values of the SN had a positive correlation with the variation in the severity of disease. 3. Hypertension and hyperhomocysteinemia were independent factors for SSLI in patients with PD.Conclusion: As PD progresses, movement disorders become more prominent, with increased structural changes to the SN, especially in patients with SSLI. Furthermore, PD patients with hypertension and hyperhomocysteinemia are more likely to have SSLI. [ABSTRACT FROM AUTHOR]