Sleep Disturbance in Rodent Models and Its Sex-Specific Implications.

Sleep disturbances, encompassing altered sleep physiology or disorders like insomnia and sleep apnea, profoundly impact physiological functions and elevate disease risk. Despite extensive research, the underlying mechanisms and sex-specific differences in sleep disorders remain elusive. While polysomnography serves as a cornerstone for human sleep studies, animal models provide invaluable insights into sleep mechanisms. However, the availability of animal models of sleep disorders is limited, with each model often representing a specific sleep issue or mechanism. Therefore, selecting appropriate animal models for sleep research is critical. Given the significant sex differences in sleep patterns and disorders, incorporating both male and female subjects in studies is essential for uncovering sex-specific mechanisms with clinical relevance. This review provides a comprehensive overview of various rodent models of sleep disturbance, including sleep deprivation, sleep fragmentation, and circadian rhythm dysfunction. We evaluate the advantages and disadvantages of each model and discuss sex differences in sleep and sleep disorders, along with potential mechanisms. We aim to advance our understanding of sleep disorders and facilitate sex-specific interventions.

EEG brain network variability is correlated with other pathophysiological indicators of critical patients in neurology intensive care unit.

Continuous electroencephalogram (cEEG) plays a crucial role in monitoring and postoperative evaluation of critical patients with extensive EEG abnormalities. Recently, the temporal variability of dynamic resting-state functional connectivity has emerged as a novel approach to understanding the pathophysiological mechanisms underlying diseases. However, little is known about the underlying temporal variability of functional connections in critical patients admitted to neurology intensive care unit (NICU). Furthermore, considering the emerging field of network physiology that emphasizes the integrated nature of human organisms, we hypothesize that this temporal variability in brain activity may be potentially linked to other physiological functions. Therefore, this study aimed to investigate network variability using fuzzy entropy in 24-hour dynamic resting-state networks of critical patients in NICU, with an emphasis on exploring spatial topology changes over time. Our findings revealed both atypical flexible and robust architectures in critical patients. Specifically, the former exhibited denser functional connectivity across the left frontal and left parietal lobes, while the latter showed predominantly short-range connections within anterior regions. These patterns of network variability deviating from normality may underlie the altered network integrity leading to loss of consciousness and cognitive impairment observed in these patients. Additionally, we explored changes in 24-hour network properties and found simultaneous decreases in brain efficiency, heart rate, and blood pressure between approximately 1 pm and 5 pm. Moreover, we observed a close relationship between temporal variability of resting-state network properties and other physiological indicators including heart rate as well as liver and kidney function. These findings suggest that the application of a temporal variability-based cEEG analysis method offers valuable insights into underlying pathophysiological mechanisms of critical patients in NICU, and may present novel avenues for their condition monitoring, intervention, and treatment.

Reduced Plasma Levels of α-Klotho and Their Correlation With Klotho Polymorphisms in Elderly Patients With Major Depressive Disorders.

Background: Recent literature suggests that α-Klotho, a widely recognized anti-aging protein, is involved in longevity as well as in many diseases, including Alzheimer's disease, and depression. Although the Klotho gene encodes α-Klotho, a single transmembrane protein with intracellular and extracellular domains, the relationship between Klotho gene polymorphism and circulating α-Klotho levels in patients with major depressive disorder (MDD) is not clear. Methods: A total of 144 MDD patients and 112 age-matched healthy controls were included in this study. The Klotho genetic polymorphisms (rs9536314, rs9527025, and rs9315202) and plasma α-Klotho levels were measured by PCR and ELISA, respectively. The severity of depressive symptoms was estimated using the Hamilton Depression Scale (HAMD). Results: We found a significantly lower level of plasma α-Klotho in the MDD patients than in controls. Among them, only elderly MDD patients (first episode) showed significantly lower α-Klotho levels than the age-matched controls, while elderly recurrent and young MDD patients showed no difference in plasma α-Klotho levels from age-matched controls. The young MDD group showed a significantly earlier onset age, higher plasma α-Klotho levels, and lower HAMD scores than those in the elderly MDD group. While the plasma α-Klotho levels were higher in rs9315202 T alleles carrier regardless age or sex, the rs9315202 T allele was negatively correlated with disease severity only in the elderly MDD patients. Conclusion: The results of our study showed that only elderly MDD patients showed a decrease in plasma α-Klotho levels along with an increase in disease severity as well as an association with the number of rs9315202 T alleles, and not young MDD patients compared to age-matched controls. Our data suggest that circulating α-Klotho levels combined with Klotho genetic polymorphisms are important in elderly MDD patients, particularly carriers of the Klotho gene rs9315202 T allele.

Brain estrogen alters the effects of the antidepressant sertraline in middle-aged female and male mice.

Estrogens are important in regulating mood, especially for females. However, whether tissue-specific estrogen, such as brain estrogen, contributes to the effects of antidepressant treatment has not been determined. The present study used middle-aged aromatase gene knockout (Ar-/-) mice or overexpression (Thy1-Ar; hGFAP-Ar) mice as brain estrogen models to investigate whether brain estrogen synthesis alters the anti-depressive behaviors of sertraline treatment. Our results showed that depletion of brain estrogen increased depressive-like behavior in females, and elevated brain estrogen reduced depression-like behavior, regardless of sex. These genotype-related behaviors correlated with alterations of monoamine metabolism in the hippocampus (HPC) and the prefrontal cortex (PFC). We also demonstrated that male and female Ar-/- mice exhibited an attenuation of sertraline-induced anti-depressive behaviors compared to wild-type (WT) mice. The present data suggest that brain estrogen alters depressive-like behaviors and changes the effectiveness of antidepressants in middle-aged mice, regardless of sex.