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Background: Sensitivity to ethanol provides an index of the predisposition to recover from unconsciousness induced by a dose of ethanol. The role of the G protein‐coupled receptor 158 (GPR158) in modulating sensitivity to the sedative‐hypnotic effect of ethanol has not been investigated. Methods: Loss of righting reflex (LORR) is a behavioral indicator of hypnosis in rodents. In this study, Gpr158−/− mice and wild‐type (WT) littermates (n = 8/genotype) were tested using LORR induced by a dose of 3.5 g/kg ethanol, an open‐field test (OFT), and a measure of blood ethanol concentration. The OFT was used to examine the role of GPR158 in the ethanol effect on motor activity in Gpr158−/− mice (n = 6/genotype). We also tested CamK2A‐Cre;Gpr158fl/fl (n = 9) and Vgat‐Cre;Gpr158fl/fl mice (n = 10) using the LORR test and OFT to compare with controls (n = 9 and 8, respectively). Results: Gpr158 deficiency prolonged the LORR duration by 110.6%, t(14) = −5.241, p = 0.0001, without altering spontaneous activity, t(14) = −0.718, p = 0.485, or ethanol metabolism, F(1, 8) = 0.259, p = 0.625. Gpr158 knockout did not change the ethanol effect on locomotion, F(1, 10) = 0.262, p = 0.62. The LORR duration increased by 69% in the conditional knockouts of Gpr158 within calcium/calmodulin‐dependent protein kinase II alpha‐positive (CamK2A+) neurons, t(16) = −2.914, p = 0.01, and by 92% in the vesicular GABA transporter‐positive (Vgat+) neurons, t(9.802) = −2.519, p = 0.023. Locomotion was not altered in Camk2A‐Cre;Gpr158fl/fl, t(16) = 0.49, p = 0.631 or Vgat‐Cre;Gpr158fl/fl mice, t(16) = 0.035, p = 0.972. Conclusions: This study reveals the key role of neuronal GPR158 in shaping sensitivity to the sedative‐hypnotic effect of ethanol. These findings contribute to our understanding of the neurobiology of ethanol intoxication. [ABSTRACT FROM AUTHOR]

Background: Some observational studies had found that shift work would increase risks of metabolic disorders, cancers, and cardiovascular diseases, but there was no homogeneous evidence of such an association between shift work and incident dementia. This study aimed to investigate whether shift work would increase the risk of dementia in a general population. Methods: One hundred seventy thousand seven hundred twenty-two employed participants without cognitive impairment or dementia at baseline recruited between 2006 and 2010 were selected from the UK Biobank cohort study. Follow-up occurred through June 2021. Shift work status at baseline was self-reported by participants and they were categorized as non-shift workers or shift workers. Among shift workers, participants were further categorized as night shift workers or shift but non-night shift workers. The primary outcome was all-cause dementia in a time-to-event analysis, and the secondary outcomes were subtypes of dementia, including Alzheimer's disease, vascular dementia, and other types of dementia. Results: In total, 716 dementia cases were observed among 170,722 participants over a median follow-up period of 12.4 years. Shift workers had an increased risk of all-cause dementia as compared with non-shift workers after multivariable adjustment (hazard ratio [HR], 1.30, 95% confidence interval [CI], 1.08–1.58); however, among shift workers, night shift work was not associated with the risk of dementia (HR, 1.04, 95% CI, 0.73–1.47). We found no significant interaction between shift work and genetic predisposition to dementia on the primary outcome (P for interaction = 0.77). Conclusions: Shift work at baseline was associated with an increased risk of all-cause dementia. Among shift workers, there was no significant association between night shift work and the risk of dementia. The increased incidence of dementia in shift workers did not differ between participants in different genetic risk strata for dementia. [ABSTRACT FROM AUTHOR]

Depressive disorder is defined as a psychiatric disease characterized by the core symptoms of anhedonia and learned helplessness. Currently, the treatment of depression still calls for medications with high effectiveness, rapid action, and few side effects, although many drugs, including fluoxetine and ketamine, have been approved for clinical usage by the Food and Drug Administration (FDA). In this study, we focused on calcitonin as an amylin receptor polypeptide, of which the antidepressant effect has not been reported, even if calcitonin gene-related peptides have been previously demonstrated to improve depressive-like behaviors in rodents. Here, the antidepressant potential of salmon calcitonin (sCT) was first evaluated in a chronic restraint stress (CRS) mouse model of depression. We observed that the immobility duration in CRS mice was significantly increased during the tail suspension test and forced swimming test. Furthermore, a single administration of sCT was found to successfully rescue depressive-like behaviors in CRS mice. Lastly, AC187 as a potent amylin receptor antagonist was applied to investigate the roles of amylin receptors in depression. We found that AC187 significantly eliminated the antidepressant effects of sCT. Taken together, our data revealed that sCT could ameliorate a depressive-like phenotype probably via the amylin signaling pathway. sCT should be considered as a potential therapeutic candidate for depressive disorder in the future. [ABSTRACT FROM AUTHOR]

Myelin abnormalities have been observed in autism spectrum disorder (ASD). In this study, we seek to discover myelin-related changes in the striatum, a key brain region responsible for core ASD features, using the 16p11.2 deletion (16p11.2±) mouse model of ASD. We found downregulated expression of multiple myelin genes and decreased myelin thickness in the striatum of 16p11.2± mice versus wild type controls. Moreover, given that myelin is the main reservoir of brain lipids and that increasing evidence has linked dysregulation of lipid metabolism to ASD, we performed lipidomic analysis and discovered decreased levels of certain species of sphingomyelin, hexosyl ceramide and their common precursor, ceramide, in 16p11.2± striatum, all of which are major myelin components. We further identified lack of ceramide synthase 2 as the possible reason behind the decrease in these lipid species. Taken together, our data suggest a role for myelin and myelin lipids in ASD development. [ABSTRACT FROM AUTHOR]

Background: Transient ischemic attack (TIA) is a brief episode of cerebral ischemia. However, if a symptom is not presented as drop attack or hemiplegia, and alarming to the patient and the physician, how short of a symptom duration would raise the concern of a physician for TIA? It will be more complicated if the location of the neurological deficit is vagrant. This report highlights a rare TIA case which presented a very short duration of migratory patchy distribution numbness. Case presentation: A middle-aged gentleman was presented with recurrent patchy distribution numbness on the right side of the body for 2 months, with the episode lasting as short as about 10 s. The location of the numbness was erratic and migratory. Magnetic resonance angiography (MRA) revealed mild stenosis on the left middle cerebral artery (MCA). Transcranial Doppler (TCD) micro-emboli monitoring detected positive micro-emboli signals (MES), leading to the confirmation of a TIA diagnosis. After a standard dual antiplatelet treatment combined with enhanced lipid reduction therapy with statins, MES disappeared on dynamic TCD emboli monitoring, and no more episodes of TIA have been noticed on the follow-ups. Conclusion: TIA caused by micro-emboli can display as recurrent migratory neurological deficit within seconds. TCD micro-emboli monitoring is very helpful to differentiate this situation from TIA mimics with follow-ups, as well as to locate unstable plague. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

Background: Transient ischemic attack (TIA) is a brief episode of cerebral ischemia. However, if a symptom is not presented as drop attack or hemiplegia, and alarming to the patient and the physician, how short of a symptom duration would raise the concern of a physician for TIA? It will be more complicated if the location of the neurological deficit is vagrant. This report highlights a rare TIA case which presented a very short duration of migratory patchy distribution numbness.Case Presentation: A middle-aged gentleman was presented with recurrent patchy distribution numbness on the right side of the body for 2 months, with the episode lasting as short as about 10 s. The location of the numbness was erratic and migratory. Magnetic resonance angiography (MRA) revealed mild stenosis on the left middle cerebral artery (MCA). Transcranial Doppler (TCD) micro-emboli monitoring detected positive micro-emboli signals (MES), leading to the confirmation of a TIA diagnosis. After a standard dual antiplatelet treatment combined with enhanced lipid reduction therapy with statins, MES disappeared on dynamic TCD emboli monitoring, and no more episodes of TIA have been noticed on the follow-ups.Conclusion: TIA caused by micro-emboli can display as recurrent migratory neurological deficit within seconds. TCD micro-emboli monitoring is very helpful to differentiate this situation from TIA mimics with follow-ups, as well as to locate unstable plague. [ABSTRACT FROM AUTHOR]

Background: The proceeding of blood pressure (BP) from normal level to the hypertension has been found to be associated with increased cardiovascular events and multiple vascular risk factors. However, whether the process is associated with increased carotid atherosclerotic plaque per se or not is still unclear.Methods: Nine hundred and forty-two participants aged from 46 to 75 were enrolled from community population in Southern China. Their metabolic risk factors, carotid intima-media thickness (cIMT) and atherosclerotic plaque formation were analyzed and stratified by different blood pressure levels according to JNC-7 or ESH/ESC-2007 classification.Results: From low BP level to higher BP level, multiple metabolic risk factors increased linearly. Prehypertension in JNC-7 classification (or normal BP and high normal BP in ESH/ESC-2007 classification) was correlated with thicker cIMT and more plaque formation than normotension (or optimal BP) (p < 0.001). After adjusting multiple metabolic factors, the differences were still significant (p < 0.05). Furthermore, prehypertensive participants had a trend to be thicker carotid IMT (OR and its 95% CI: 1.65, 0.97-2.82, p = 0.067) and significantly higher carotid plaque occurrence (OR and its 95% CI: 2.36, 1.43-3.88, p = 0.001) than normotensive ones. However, there was no significant difference of cIMT and plaque formation between normal BP and high normal BP (p > 0.05). Plaque formation in prehypertension was as significant as that in hypertension.Conclusion: Prehypertension is associated with significantly increased carotid atherosclerotic plaque and is a primary stratify risk factor for carotid atherosclerosis which could cause ischemic stroke in middle-aged and elderly population in Southern China. [ABSTRACT FROM AUTHOR]