Prediction Model for Cognitive Impairment among Disabled Older Adults: A Development and Validation Study.

Disabled older adults exhibited a higher risk for cognitive impairment. Early identification is crucial in alleviating the disease burden. This study aims to develop and validate a prediction model for identifying cognitive impairment among disabled older adults. A total of 2138, 501, and 746 participants were included in the development set and two external validation sets. Logistic regression, support vector machine, random forest, and XGBoost were introduced to develop the prediction model. A nomogram was further established to demonstrate the prediction model directly and vividly. Logistic regression exhibited better predictive performance on the test set with an area under the curve of 0.875. It maintained a high level of precision (0.808), specification (0.788), sensitivity (0.770), and F1-score (0.788) compared with the machine learning models. We further simplified and established a nomogram based on the logistic regression, comprising five variables: age, daily living activities, instrumental activity of daily living, hearing impairment, and visual impairment. The areas under the curve of the nomogram were 0.871, 0.825, and 0.863 in the internal and two external validation sets, respectively. This nomogram effectively identifies the risk of cognitive impairment in disabled older adults.

Simulation Study for the Adsorption of Carbon Disulfide on Hydroxyl Modified Activated Carbon.

In this study, grand canonical Monte Carlo simulations (GCMC) and molecular dynamics simulations (MD) were used to construct models of activated carbon with hydroxyl-modified hexachlorobenzene basic unit contents of 0%, 12.5%, 25%, 35% and 50%. The mechanism of adsorption of carbon disulfide (CS2) by hydroxyl-modified activated carbon was then studied. It is found that the introduction of hydroxyl functional groups will improve the adsorption capacity of activated carbon for carbon disulfide. As far as the simulation results are concerned, the activated carbon model containing 25% hydroxyl modified activated carbon basic units has the best adsorption performance for carbon disulfide molecules at 318 K and atmospheric pressure. At the same time, the changes in the porosity, accessible surface area of the solvent, ultimate diameter and maximum pore diameter of the activated carbon model also led to great differences in the diffusion coefficient of carbon disulfide molecules in different hydroxyl-modified activated carbons. However, the same adsorption heat and temperature had little effect on the adsorption of carbon disulfide molecules.

Molecular Simulation to Explore the Dissolution Behavior of Sulfur in Carbon Disulfide.

Soluble sulfur (S8) and insoluble sulfur (IS) have different application fields, and molecular dynamics simulation can reveal their differences in solubility in solvents. It is found that in the simulated carbon disulfide (CS2) solvent, soluble sulfur in the form of clusters mainly promotes the dissolution of clusters through van der Waals interaction between solvent molecules (CS2) and S8, and the solubility gradually increases with the increase in temperature. However, the strong interaction between polymer chains of insoluble sulfur in the form of polymer hinders the diffusion of IS into CS2 solvent, which is not conducive to high-temperature dissolution. The simulated solubility parameter shows that the solubility parameter of soluble sulfur is closer to that of the solvent, which is consistent with the above explanation that soluble sulfur is easy to dissolve.

Starvation Affects the Muscular Morphology, Antioxidant Enzyme Activity, Expression of Lipid Metabolism-Related Genes, and Transcriptomic Profile of Javelin Goby (Synechogobius hasta).

Fish in natural and cultivated environments can be challenged by starvation. However, inducing starvation in a controlled manner cannot only reduce feed consumption but also reduces aquatic eutrophication and even improves farmed fish quality. This study investigated the effects of starvation on the muscular function, morphology, and regulatory signaling in javelin goby (Synechogobius hasta) by evaluating the biochemical, histological, antioxidant, and transcriptional changes in the musculature of S. hasta subjected to 3, 7, and 14 days fasting. The muscle glycogen and triglyceride levels in S. hasta were gradually reduced under starvation, reaching their lowest at the end of the trial (P < 0.05). The levels of glutathione and superoxide dismutase were significantly elevated after 3-7 days of starvation (P < 0.05), but later returned to the level of the control group. The muscle of starved S. hasta developed structural abnormalities in some areas after 7 days of food deprivation, and more vacuolation and more atrophic myofibers were observed in 14-day fasted fish. The transcript levels of stearoyl-CoA desaturase 1 (scd1), the key gene involved in the biosynthesis of monounsaturated fatty acids, were markedly lower in the groups starved for 7 or more days (P < 0.05). However, the relative expressions of genes associated with lipolysis were decreased in the fasting experiment (P < 0.05). Similar declines in the transcriptional response to starvation were found in muscle fatp1 and ppar γ abundance (P < 0.05). Furthermore, the de novo transcriptome of muscle tissue from the control, 3-day and 14-day starved S. hasta generated 79,255 unigenes. The numbers of differentially expressed genes (DEGs) identified by pairwise comparisons among three groups were 3276, 7354, and 542, respectively. The enrichment analysis revealed that the DEGs were primarily involved in metabolism-related pathways, including ribosome, TCA pathway, and pyruvate metabolism. Moreover, the qRT-PCR results of 12 DEGs validated the expression trends observed in the RNA-seq data. Taken together, these findings demonstrated the specific phenotypical and molecular responses of muscular function and morphology in starved S. hasta, which may offer preliminary reference data for optimizing operational strategies incorporating fasting/refeeding cycles in aquaculture.

Label-free non-invasive subwavelength-resolution imaging using yeast cells as biological lenses.

There is a growing interest to use live cells to replace the widely used non-biological microsphere lenses. In this work, we demonstrate the use of yeast cells for such imaging purpose. Using fiber-based optical trapping technique, we trap a chain of three yeast cells and bring them to the vicinity of imaging objects. These yeast cells work as near-field magnifying lenses and simultaneously pick up the sub-diffraction information of the nanoscale objects under each cell and project them into the far-field. The experimental results demonstrated that Blu-ray disc of 100 nm feature can be clearly resolved in a parallel manner by each cell.

Anti-stress effects of combined block of glucocorticoid and mineralocorticoid receptors in the paraventricular nucleus of the hypothalamus.

BACKGROUND AND PURPOSE: Mineralocorticoid receptors (MRs), glucocorticoid receptors (GRs) and corticotropin-releasing factor (CRF) in the paraventricular nucleus of hypothalamus (PVN) are involved in the response to stress. The present study investigated the role of GRs and MRs in the PVN in regulating depressive and anxiety-like behaviours. EXPERIMENTAL APPROACH: To model chronic stress, rats were exposed to corticosterone treatment via drinking water for 21 days, and GR antagonist RU486 and MR antagonist spironolactone, alone and combined, were directly injected in the PVN daily for the last 7 days of corticosterone treatment. Behavioural tests were run on days 22 and 23. Depressive- and anxiety-like behaviours were evaluated in forced swim test, sucrose preference test, novelty-suppressed feeding test and social interaction test. The expression of GRs, MRs and CRF were detected by western blot. KEY RESULTS: Rats exposed to corticosterone exhibited depressive- and anxiety-like behaviours. The expression of GRs and MRs decreased, and CRF levels increased in the PVN. The intra-PVN administration of RU486 increased the levels of GRs and CRF without influencing depressive- or anxiety-like behaviours. The spironolactone-treated group exhibited an increase in MRs without influencing GRs and CRF in the PVN and improved anxiety-like behaviours. Interestingly, the intra-PVN administration of RU486 and spironolactone combined restored expression of GRs, MRs and CRF and improved depressive- and anxiety-like behaviours. CONCLUSION AND IMPLICATIONS: In this rat model of stress, the simultaneous restoration of GRs, MRs and CRF in the PVN might play an important role in the treatment of depression and anxiety.

Index tracking strategy based on mixed-frequency financial data.

To obtain market average return, investment managers need to construct index tracking portfolio to replicate target index. Currently, most literatures use financial data that has homogenous frequency when constructing the index tracking portfolio. To make up for this limitation, we propose a methodology based on mixed-frequency financial data, called FACTOR-MIDAS-POET model. The proposed model can utilize the intraday return data, daily risk factors data and monthly or quarterly macro economy data, simultaneously. Meanwhile, the out-of-sample analysis demonstrates that our model can improve the tracking accuracy.

Prophylactic effects of sporoderm-removed Ganoderma lucidum spores in a rat model of streptozotocin-induced sporadic Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (G. lucidum, Lingzhi), also known as "immortality mushroom" has been broadly used to improve health and longevity for thousands of years in Asia. G. lucidum and its spores have been used to promote health, based on its broad pharmacological and therapeutic activity. This species is recorded in Chinese traditional formula as a nootropic and has been suggested to improve cognitive dysfunction in Alzheimer's disease. However, little is known about the nootropic effects and molecular mechanism of action of G. lucidum spores. AIM OF THE STUDY: The present study investigated the protective effects of sporoderm-deficient Ganoderma lucidum spores (RGLS) against learning and memory impairments and its mechanism of action. MATERIALS AND METHODS: In the Morris water maze, the effects of RGLS on learning and memory impairments were evaluated in a rat model of sporadic Alzheimer's disease that was induced by an intracerebroventricular injection of streptozotocin (STZ). Changes in amyloid ß (Aß) expression, Tau expression and phosphorylation, brain-derived neurotrophic factor (BDNF), and the BDNF receptor tropomyosin-related kinase B (TrkB) in the hippocampus were evaluated by Western blot. RESULTS: Treatment with RGLS (360 and 720 mg/kg) significantly enhanced memory in the rat model of STZ-induced sporadic Alzheimer's disease and reversed the STZ-induced increases in Aß expression and Tau protein expression and phosphorylation at Ser199, Ser202, and Ser396. The STZ-induced decreases in neurotrophic factors, including BDNF, TrkB and TrkB phosphorylation at Tyr816, were reversed by treatment with RGLS. CONCLUSION: These findings indicate that RGLS prevented learning and memory impairments in the present rat model of STZ-induced sporadic Alzheimer's disease, and these effects depended on a decrease in Aß expression and Tau hyperphosphorylation and the modulation of BDNF-TrkB signaling in the hippocampus.

Vibration measurement technology based on the reverse point recognition algorithm for laser self-mixing interference.

The self-mixing interference (SMI) signal carries the information of the external moving object, which has great physical significance and application prospects for extracting and analyzing the information of the external object. In this paper, we propose a vibration measurement method based on a reverse point recognition algorithm on the SMI laser signal. By extracting and analyzing the hill and valley values of the SMI signal to determine the reverse point, combined with the semifringe counting method, the vibration information of external objects can be accurately extracted. The method we propose simplifies the displacement reconstruction process with high accuracy. The simulation and experimental results show that this method can achieve high-precision measurements of microvibration with an absolute error of less than 19 nm.

A common neuronal mechanism of hypertension and sleep disturbances in spontaneously hypertensive rats: Role of orexinergic neurons.

Epidemiologic studies have shown that sleep disorders are associated with the development of hypertension. The present study investigated dynamic changes in sleep patterns during the development of hypertension across the lifespan in spontaneously hypertensive rats (SHRs) and the neural mechanism that underlies these comorbidities, with a focus on the orexinergic system. Blood pressure in rats was measured using a noninvasive blood pressure tail cuff. Sleep was monitored by electroencephalographic and electromyographic recordings. Immunohistochemistry was used to detect the density and activity of orexinergic neurons in the perifornical nucleus. Hcrt2-SAP (400 or 800 ng) was microinjected in the lateral hypothalamus to lesion orexinergic neurons. Compared with Wistar-Kyoto rats, SHRs exhibited various patterns of sleep disturbances. In SHRs, dynamic changes in hypersomnia in the rats' active phase was not synchronized with the development of hypertension, but hyperarousal in the inactive phase and difficulties in falling asleep were observed concurrently with the development of hypertension. Furthermore, the density and activity of orexinergic neurons in the perifornical nucleus were significantly higher in SHRs than in age-matched Wistar-Kyoto rats. The reduction of orexinergic neurons in the lateral hypothalamus partially ameliorated the development of hypertension and prevented difficulties in falling asleep in SHRs. These results indicate that although the correlation between sleep disturbances and hypertension is very complex, common mechanisms may underlie these comorbidities in SHRs. Overactivity of the orexin system may be one such common mechanism.

Serotonergic system may be involved in alterations of sleep homeostasis in spontaneously hypertensive rats.

Hypertension is associated with sleep disorders. Spontaneously hypertensive rats are derived from Wistar-Kyoto rats and widely used in research on hypertension. The present study investigated the propensity to sleep and electroencephalographic spectrum changes over 24 hr in spontaneously hypertensive rats, and proposed the involvement of the serotonergic system in these alterations. Time-course analysis showed that spontaneously hypertensive rats exhibit hyperarousal during the light phase but hypersomnia during the dark phase. Spontaneously hypertensive rats also exhibited less slight fluctuation in electroencephalographic delta power density over 24 hr as compared with Wistar-Kyoto rats, suggesting that the accumulation or elimination of sleep pressure was disrupted. Sleep deprivation disrupted the regulation of sleep homeostasis in spontaneously hypertensive rats, reflected by less sleep time and poor sleep quality during the recovery period. The density and activity of serotonergic neurons in the dorsal raphe nucleus were higher in spontaneously hypertensive rats compared with Wistar-Kyoto rats. Interestingly, we observed the absence of fluctuations in 5-hydroxytryptamine and 5-hydroxyindoleacetic acid across the sleep, wake, sleep deprivation and sleep recovery stages in spontaneously hypertensive rats, which were dramatically different from Wistar-Kyoto rats. These results indicate that the disruption of sleep-wake pattern and sleep homeostasis in spontaneously hypertensive rats might be related to abnormalities of the serotonergic system.

Secondary envelope extraction based on multiple Hilbert transforms for laser self-mixing micro-vibration measurement.

This paper presents a method that can be applied to weak feedback and full-range moderate feedback in the field of self-mixing interference measurement, and the target motion displacement can be obtained by multiple Hilbert transforms of the signal after the secondary envelope extraction. Simulations and experiments of multiple micro-vibration measurements were performed with different optical feedback factors, and the results were consistent with theoretical analysis. This method effectively eliminates the impact of the self-mixing interference signal with fringe shift on micro-vibration reconstruction.

Neuropharmacological Effect and Clinical Applications of Ganoderma (Lingzhi).

Ganoderma lucidum (G. lucidum, Lingzhi) is a kind of medical mushroom with various pharmacological compounds. It has been used for clinical applications for thousands of years as a highly nutritious and significantly effective medicinal herb. Compared with its immunomodulatory effect, there are a few studies on the neuropharmacological actions of Ganoderma, and the mechanism has not been fully elucidated. As far as we know, Ganoderma regulate the central nervous system (CNS) at least in part through its immunomodulatory activity. The neuropharmacological effects of G. lucidum mainly include but not limited to sedative and hypnotic, neuroprotective, antinociceptive and analgesic, antiepileptic, and antidepressant effects. Clinical trials of G. lucidum in the patients with these disorders are still rare. To date, there are no Ganoderma-related drugs approved by the US Food and Drug Administration (FDA). In this chapter, we will summarize and elucidate recent progress of such effects of Ganoderma and its ingredients from both the preclinical and clinical points of view.

Methylation of RUNX3 and RASSF1A and the risk of Malignancy in small solitary pulmonary nodules.

BACKGROUND: This study aimed to evaluate the methylation of RUNX3 and RASSF1A gene promoter regions as a marker to distinguish between benign and malignant of small solitary pulmonary nodule (SPN) ≤10 mm in size. MATERIALS AND METHODS: A total of 147 patients with pathologically confirmed SPNs were enrolled. DNA samples were extracted from biopsy tissues or serum. Methylation of RUNX3 and RASSF1A gene promoter regions was detected by the methylation-specific polymerase chain reaction. The expression of RUNX3 and RASSF1A in SPN tissues was detected by western blot. RESULTS: Of the 147 patients, 89 had benign SPNs and 58 had malignant SPNs. The rate of serum RUNX3 and RASSF1A gene methylation in malignant SPNs was significantly higher than that in benign SPNs (65.5% vs. 12.3%, and 67.2% vs. 10.1%, respectively; P < 0.05). The expression of RUNX3 and RASSF1A in malignant SPN tissues was lower than that in benign SPN tissues. The hypermethylation status of RUNX3 or RASSF1A genes was not significantly associated with age, gender, and smoking. CONCLUSIONS: The methylation level of the RUNX3 and RASSF1A gene promoter regions is a promising marker for assessing SPNs.

Ginsenoside Rg1 promotes sleep in rats by modulating the noradrenergic system in the locus coeruleus and serotonergic system in the dorsal raphe nucleus.

Panax ginseng Mayer has been used as tranquilizer to improve sleep disorder, but its active component is not defined. This study investigated the effects of the most abundant constituents of P. ginseng-protopanaxatriol ginsenoside Rg1 and protopanaxadiol ginsenoside Rb1-on sleep in rats. Male Sprague-Dawley rats received intragastrical injections of Rg1 and Rb1 for 3 days (5, 10, and 20 mg/kg/day). Sleep parameters were analyzed using electroencephalogram and electromyogram. Neuronal activation and monoaminergic neurotransmitters were evaluated using immunohistochemical fluorescence staining and HPLC, respectively. Rg1 treatment significantly increased the duration of total sleep, rapid eye movement sleep (REMS) and Non-REMS at the dose of 5, 10 and 20 mg/kg/day, and also prolonged the proportion of slow-wave sleep in the total sleep. The Non-REMS episodes were increased and the mean duration of each wakefulness episode was depressed by Rg1 treatment. Rb1 had no effect on sleep parameters. Rg1 treatment decreased the activity of noradrenergic neurons in locus coeruleus (LC) and increased the activity of serotonergic neurons in the dorsal raphe nucleus (DRN). Besides, Rg1 depressed extracellular norepinephrine concentrations in both LC and DRN and in other sleep-regulating brain regions of which functions can be modulated by monoaminergic neurotransmitters discharged from projecting noradrenergic and serotonergic neurons. In conclusion, Rg1 might be the sleep-promoting component in P. ginseng and its mechanism may be related to the modulation of noradrenergic and serotonergic systems. Our findings also highlight functional differences between Rg1 and Rb1.

Melanin-Concentrating Hormone (MCH) and MCH-R1 in the Locus Coeruleus May Be Involved in the Regulation of Depressive-Like Behavior.

Background: Previous anatomical and behavioral studies have shown that melanin-concentrating hormone is involved in the modulation of emotional states. However, little is known about brain regions other than the dorsal raphe nucleus that relate the melanin-concentrating hormone-ergic system to depressive states. Numerous studies have shown that the locus coeruleus is involved in the regulation of depression and sleep. Although direct physiological evidence is lacking, previous studies suggest that melanin-concentrating hormone release in the locus coeruleus decreases neuronal discharge. However, remaining unclear is whether the melanin-concentrating hormone-ergic system in the locus coeruleus is related to depressive-like behavior. Method: We treated rats with an intra-locus coeruleus injection of melanin-concentrating hormone, intracerebroventricular injection of melanin-concentrating hormone, or chronic subcutaneous injections of corticosterone to induce different depressive-like phenotypes. We then assessed the effects of the melanin-concentrating hormone receptor 1 antagonist SNAP-94847 on depressive-like behavior in the forced swim test and the sucrose preference test. Results: The intra-locus coeruleus and intracerebroventricular injections of melanin-concentrating hormone and chronic injections of corticosterone increased immobility time in the forced swim test and decreased sucrose preference in the sucrose preference test. All these depressive-like behaviors were reversed by an intra-locus coeruleus microinjection of SNAP-94847. Conclusions: These results suggest that the melanin-concentrating hormone-ergic system in the locus coeruleus might play an important role in the regulation of depressive-like behavior.

Depression-like behaviors induced by chronic corticosterone exposure via drinking water: Time-course analysis.

Hypothalamic-pituitary-adrenal (HPA) axis activity is commonly dysregulated in stress-related psychiatric disorders. The corticosterone rat model was developed to understand the influence of stress on depression-like symptomatology. To further understand the effects of corticosterone on the development of depression-like behavior, rats were continuously exposed to corticosterone (200 µg/ml) or vehicle via drinking water daily for 21 days. The rats underwent a series of behavioral tests, and electroencephalographical recordings were performed after 7, 14, and 21 days of treatment. The measurements included immobility time (i.e., despair) in the forced swim test, locomotor activity in the open field test, sucrose consumption (i.e., anhedonia) in the sucrose preference test, and sleep-wake parameters. The rats in the 7-day corticosterone exposure group exhibited depression-like behavior, including increases in despair, anhedonia, anxiety, and sleep impairments. The rats in the 14-day corticosterone exposure group exhibited normal patterns of behavior and sleep structure. When corticosterone exposure was extended to 21 days, depression-like symptoms recurred, including despair, anhedonia, anxiety, and sleep disturbances. Overall, the present study observed U-shaped depression-like effects across 3 weeks of corticosterone exposure via drinking water.

MEG-3-mediated Wnt/ß-catenin signaling pathway controls the inhibition of tunicamycin-mediated viability in glioblastoma.

Glioblastoma is the most common primary brain carcinoma and leads to a poor survival rate of patients worldwide. Results of previous studies have suggested that tunicamycin may inhibit aggressiveness by promoting apoptosis of glioblastoma cells. In the present study, the effects of tunicamycin and its potential molecular mechanisms underlying the viability and aggressiveness of glioblastoma cells were investigated. Western blot analysis, the reverse transcription-quantitative polymerase chain reaction, immunohistochemistry, apoptosis assays and immunofluorescence were employed to examine the effects of tunicamycin on apoptosis, viability, aggressiveness and cell cycle arrest of glioblastoma cells by downregulation of the expression levels of fibronectin and epithelial cadherin. In vitro experiments demonstrated that tunicamycin significantly inhibited the viability, migration and invasion of glioblastoma cells. Results demonstrated that tunicamycin administration promoted apoptosis of glioblastoma cells through the upregulation of poly(ADP-ribose) polymerase and caspase-9. Cell cycle assays revealed that tunicamycin suppressed the proliferation of, and induced cell cycle arrest at S phase in, glioblastoma cells. Additionally, tunicamycin increased the expression of maternally expressed gene-3 (MEG-3) and wingless/integrated (Wnt)/ß-catenin in glioblastoma cells. Results also indicated that tunicamycin administration promoted the Wnt/ß-catenin signaling pathway in glioblastoma cells. Knockdown of MEG-3 inhibited tunicamycin-mediated downregulation of the Wnt/ß-catenin signaling pathway, which was inhibited further by tunicamycin-mediated inhibition of viability and aggressiveness in glioblastoma. In vivo assays demonstrated that tunicamycin treatment significantly inhibited tumor viability and promoted apoptosis, which further led to an increased survival rate of tumor-bearing mice compared with that of the control group. In conclusion, these results indicate that tunicamycin may inhibit the viability and aggressiveness by regulating MEG-3-mediated Wnt/ß-catenin signaling, suggesting that tunicamycin may be a potential anticancer agent for glioblastoma therapy.

Intracerebroventricular streptozotocin-induced Alzheimer's disease-like sleep disorders in rats: Role of the GABAergic system in the parabrachial complex.

AIM: Sleep disorders are common in Alzheimer's disease (AD) and assumed to directly influence cognitive function and disease progression. This study evaluated sleep characteristics in a rat model of AD that was induced by intracerebroventricular streptozotocin (STZ) administration and assessed the possible underlying mechanisms. METHODS: Cognition ability was assessed in the Morris water maze in rats. Sleep parameters were analyzed by electroencephalographic and electromyographic recordings. Neuronal activity in brain areas that regulate sleep-wake states was evaluated by double-staining immunohistochemistry. High-performance liquid chromatography with electrochemical detection was used to detect neurotransmitter levels. RESULTS: Fourteen days after the STZ injection, the rats exhibited sleep disorders that were similar to those in AD patients, reflected by a significant increase in wakefulness and decreases in nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. The c-Fos expression analysis indicated that neuronal activity and the number of neurons in the dorsal raphe nucleus and locus coeruleus decreased in STZ-injected rats. In the ventrolateral preoptic nucleus (VLPO), the activity of γ-aminobutyric acid (GABA) neurons was suppressed. In the arousal-driving parabrachial nucleus (PBN), GABAergic activity was suppressed, whereas glutamatergic activity was promoted. The neurotransmitter analysis revealed a reduction in GABA in the VLPO and PBN and elevation of glutamate in the PBN. A direct injection of the GABAA receptor antagonist bicuculline in the PBN in normal rats induced a similar pattern of sleep disorder as in STZ-injected rats. A microinjection of GABA in the PBN improved sleep disorders that were induced by STZ. CONCLUSION: These results suggest that the reduction in GABAergic inhibition in the PBN and VLPO may be involved in sleep disorders that are induced by STZ. Our novel findings encourage further studies that investigate mechanisms of sleep regulation in sporadic AD.

Sleep patterns deteriorate over time in chronic corticosterone-treated rats.

Repeated corticosterone (CORT) injections reliably produce depressive-like behavior in rodents. Our previous study showed that sleep parameters were altered in rats after daily injections of CORT for 7 days, and sleep disturbances appeared to be correlated with depressive-like behavior. The aim of the present study was to investigate time-dependent correlations between changes in sleep parameters and the formation of depressive-like behavior in rats after more prolonged treatment with CORT. Rats received daily injections of CORT (40 mg/kg, s.c.) for 7, 14, or 21 days. Electroencephalographic recordings were performed to study sleep parameters. The sucrose preference test and forced swim test were performed to evaluate depressive-like behavior. Western blot was used to detect protein levels. Our results showed that 7-day CORT treatment resulted in no significant depressive-like behavior or changes in rapid-eye-movement (REM) sleep. However, the duration of non-REM sleep significantly decreased, tyrosine hydroxylase (TH) levels significantly increased, and glucocorticoid receptor (GR) expression decreased in the locus coeruleus. Treatment with CORT for 14 and 21 days increased depressive-like behavior, enhanced REM sleep, shortened REM sleep latency, decreased TH and GR levels, and increased the levels of the chaperone FK506 binding protein 51 (FKBP51) in the locus coeruleus. These results indicate that the development of depression after chronic CORT treatment may be related to the formation of sleep disorders. Abnormalities of REM sleep may be a characteristic of sleep in models of depression that is induced by chronic CORT administration in rats. The noradrenergic system and GR pathway in the locus coeruleus may be involved in the formation of depression concomitant with sleep disturbances.