scholarly journals Effects of Chronic REM Sleep Restriction on D1Receptor and Related Signal Pathways in Rat Prefrontal Cortex

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yan Han ◽  
Xiaosa Wen ◽  
Fei Rong ◽  
Xinmin Chen ◽  
Ruying Ouyang ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Rem Sleep ◽  
Molecular Mechanisms ◽  
Sleep Restriction ◽  
Signal Pathways ◽  
Neural Function ◽  
Multiple Platform ◽  
Pka Pathway ◽  
Chronic Sleep ◽  
Neural Dysfunction

The prefrontal cortex (PFC) mediates cognitive function that is sensitive to disruption by sleep loss, and molecular mechanisms regulating neural dysfunction induced by chronic sleep restriction (CSR), particularly in the PFC, have yet to be completely understood. The aim of the present study was to investigate the effect of chronic REM sleep restriction (REM-CSR) on the D1receptor (D1R) and key molecules in D1R’ signal pathways in PFC. We employed the modified multiple platform method to create the REM-CSR rat model. The ultrastructure of PFC was observed by electron microscopy. HPLC was performed to measure the DA level in PFC. The expressions of genes and proteins of related molecules were assayed by real-time PCR and Western blot, respectively. The general state and morphology of PFC in rats were changed by CSR, and DA level and the expression of D1R in PFC were markedly decreased (P<0.01,P<0.05); the expression of phosphor-PKAcαwas significantly lowered in CSR rats (P<0.05). The present results suggested that the alteration of neuropathology and D1R expression in PFC may be associated with CSR induced cognitive dysfunction, and the PKA pathway of D1R may play an important role in the impairment of advanced neural function.

Curcumin to abrogate structural changes in the locus coeruleus following chronic sleep restriction in rats (Preprint)

2021 ◽  
Author(s):  
Ali-Mohammad Kamali ◽  
Fatemeh Karimi ◽  
Ali Noorafshan ◽  
Azam Soleimani ◽  
Saied Karbalay-Doust ◽  
...  
Keyword(s):  
Locus Coeruleus ◽  
Structural Changes ◽  
Human Subjects ◽  
Grid Floor ◽  
Wire Mesh ◽  
Male Rats ◽  
Sleep Restriction ◽  
Neuroprotective Effects ◽  
Multiple Platform ◽  
Chronic Sleep

UNSTRUCTURED This study examined the consequences of chronic sleep restriction (CSR) with or without curcumin treatment on quantitative histomorphological correlates of the locus coeruleus (LC) nucleus using stereological techniques. Male rats were assigned to five groups including: 1-control (C), 2- curcumin (CUR), 3- grid floor (GF), 4- CSR and 5- CSR+ curcumin (CUR) (100 mg/kg/day). Animals in the GF group were placed on wire-mesh grids while in the CSR box (modified multiple platform paradigm). After a period of 21 days, rats were sacrificed with their brains excised and assessed using stereological procedures. Our findings revealed a 22%, 45% and 47% reduction in the total volume, the total number of neurons and glial cells of LC in CSR group as compared to the control groups, respectively (p < 0.01). Such structural changes were abrogated in the CSR+CUR compared to the CSR group. The study outcome proposed potential neuroprotective effects of CUR in our sleep-restricted rat model. Further translational approaches would shed more light on the possible clinical significance of such finding in human subjects with chronic sleep loss including those with intensive shift-work schedules.

scholarly journals Exploring Molecular Mechanisms Involved in the Development of the Depression-Like Phenotype in Interleukin-18-Deficient Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Kyosuke Yamanishi ◽  
Masahiro Miyauchi ◽  
Keiichiro Mukai ◽  
Takuya Hashimoto ◽  
Noriko Uwa ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Molecular Mechanisms ◽  
Depressive Disorders ◽  
Psychiatric Symptoms ◽  
Neural Function ◽  
Mild Stress ◽  
Interleukin 18 ◽  
Human Brain Tissue ◽  
The Impact ◽  
The Brain

Interleukin-18 (IL-18) is an inflammatory cytokine that has been linked to energy homeostasis and psychiatric symptoms such as depression and cognitive impairment. We previously revealed that deficiency in IL-18 led to hippocampal abnormalities and resulted in depression-like symptoms. However, the impact of IL-18 deficiency on other brain regions remains to be clarified. In this study, we first sought to confirm that IL-18 expression in neural cells can be found in human brain tissue. Subsequently, we examined the expression of genes in the prefrontal cortex of Il18−/− mice and compared it with gene expression in mice subjected to a chronic mild stress model of depression. Extracted genes were further analyzed using Ingenuity® Pathway Analysis, in which 18 genes common to both the chronic mild stressed model and Il18−/− mice were identified. Of those, 16 were significantly differentially expressed between Il18+/+ and Il18−/− mice. We additionally measured protein expression of α-2-HS-glycoprotein (AHSG) and transthyretin (TTR) in serum and the brain. In the prefrontal cortex of Il18−/− mice, TTR but not AHSG was significantly decreased. Conversely, in the serum of Il18−/− mice, AHSG was significantly increased but not TTR. Therefore, our results suggest that in IL-18-deficit conditions, TTR in the brain is one of the mediators causally related to depression, and AHSG in peripheral organs is one of the regulators inducing energy imbalance. Moreover, this study suggests a possible “signpost” to clarify the molecular mechanisms commonly underlying the immune system, energy metabolism, neural function, and depressive disorders.

scholarly journals Residual, differential neurobehavioral deficits linger after multiple recovery nights following chronic sleep restriction or acute total sleep deprivation

SLEEP ◽  
2020 ◽  
Author(s):  
Erika M Yamazaki ◽  
Caroline A Antler ◽  
Charlotte R Lasek ◽  
Namni Goel
Keyword(s):  
Sleep Deprivation ◽  
Response Speed ◽  
Sleep Loss ◽  
Sleep Restriction ◽  
Total Sleep Deprivation ◽  
Psychomotor Vigilance Test ◽  
Recovery Sleep ◽  
Time In Bed ◽  
Neurobehavioral Deficits ◽  
Chronic Sleep

Abstract Study Objectives The amount of recovery sleep needed to fully restore well-established neurobehavioral deficits from sleep loss remains unknown, as does whether the recovery pattern differs across measures after total sleep deprivation (TSD) and chronic sleep restriction (SR). Methods In total, 83 adults received two baseline nights (10–12-hour time in bed [TIB]) followed by five 4-hour TIB SR nights or 36-hour TSD and four recovery nights (R1–R4; 12-hour TIB). Neurobehavioral tests were completed every 2 hours during wakefulness and a Maintenance of Wakefulness Test measured physiological sleepiness. Polysomnography was collected on B2, R1, and R4 nights. Results TSD and SR produced significant deficits in cognitive performance, increases in self-reported sleepiness and fatigue, decreases in vigor, and increases in physiological sleepiness. Neurobehavioral recovery from SR occurred after R1 and was maintained for all measures except Psychomotor Vigilance Test (PVT) lapses and response speed, which failed to completely recover. Neurobehavioral recovery from TSD occurred after R1 and was maintained for all cognitive and self-reported measures, except for vigor. After TSD and SR, R1 recovery sleep was longer and of higher efficiency and better quality than R4 recovery sleep. Conclusions PVT impairments from SR failed to reverse completely; by contrast, vigor did not recover after TSD; all other deficits were reversed after sleep loss. These results suggest that TSD and SR induce sustained, differential biological, physiological, and/or neural changes, which remarkably are not reversed with chronic, long-duration recovery sleep. Our findings have critical implications for the population at large and for military and health professionals.

Homeostatic Response to Sleep Restriction in Adolescents

SLEEP ◽  
2021 ◽  
Author(s):  
Jelena Skorucak ◽  
Nathan Weber ◽  
Mary A Carskadon ◽  
Chelsea Reynolds ◽  
Scott Coussens ◽  
...  
Keyword(s):  
Slow Wave ◽  
Process Model ◽  
Animal Studies ◽  
Sleep Restriction ◽  
Sleep Regulation ◽  
Homeostatic Process ◽  
Sleep Homeostasis ◽  
High Prevalence ◽  
Homeostatic Response ◽  
Chronic Sleep

Abstract The high prevalence of chronic sleep restriction in adolescents underscores the importance of understanding how adolescent sleep is regulated under such conditions. One component of sleep regulation is a homeostatic process: if sleep is restricted, then sleep intensity increases. Our knowledge of this process is primarily informed by total sleep deprivation studies and has been incorporated in mathematical models of human sleep regulation. Several animal studies, however, suggest that adaptation occurs in chronic sleep restriction conditions, showing an attenuated or even decreased homeostatic response. We investigated the homeostatic response of adolescents to different sleep opportunities. Thirty-four participants were allocated to one of three groups with 5, 7.5 or 10 h of sleep opportunity per night for 5 nights. Each group underwent a protocol of 9 nights designed to mimic a school week between 2 weekends: 2 baseline nights (10 h sleep opportunity), 5 condition nights (5, 7.5 or 10 h), and two recovery nights (10 h). Measures of sleep homeostasis (slow-wave activity and slow-wave energy) were calculated from frontal and central EEG derivations and compared to predictions derived from simulations of the homeostatic process of the two-process model of sleep regulation. Only minor differences were found between empirical data and model predictions, indicating that sleep homeostasis is preserved under chronic sleep restriction in adolescents. These findings improve our understanding of effects of repetitive short sleep in adolescents.

Cancer cachexia: molecular mechanism and pharmacological management

2021 ◽  
Vol 478 (9) ◽  
pp. 1663-1688
Author(s):  
Yonghua Li ◽  
Huan Jin ◽  
Yibing Chen ◽  
Ting Huang ◽  
Yanjun Mi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cancer Cachexia ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Life Quality ◽  
Signal Pathways ◽  
Pharmacological Management ◽  
Early Phase Trials ◽  
Molecular Substrates ◽  
Underlying Mechanisms

Cancer cachexia often occurs in malignant tumors and is a multifactorial and complex symptom characterized by wasting of skeletal muscle and adipose tissue, resulting in weight loss, poor life quality and shorter survival. The pathogenic mechanism of cancer cachexia is complex, involving a variety of molecular substrates and signal pathways. Advancements in understanding the molecular mechanisms of cancer cachexia have provided a platform for the development of new targeted therapies. Although recent outcomes of early-phase trials have showed that several drugs presented an ideal curative effect, monotherapy cannot be entirely satisfactory in the treatment of cachexia-associated symptoms due to its complex and multifactorial pathogenesis. Therefore, the lack of definitive therapeutic strategies for cancer cachexia emphasizes the need to develop a better understanding of the underlying mechanisms. Increasing evidences show that the progression of cachexia is associated with metabolic alternations, which mainly include excessive energy expenditure, increased proteolysis and mitochondrial dysfunction. In this review, we provided an overview of the key mechanisms of cancer cachexia, with a major focus on muscle atrophy, adipose tissue wasting, anorexia and fatigue and updated the latest progress of pharmacological management of cancer cachexia, thereby further advancing the interventions that can counteract cancer cachexia.

scholarly journals NNK-Induced Lung Tumors: A Review of Animal Model

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Hua-Chuan Zheng ◽  
Yasuo Takano
Keyword(s):  
Lung Cancer ◽  
Animal Model ◽  
Animal Models ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Genetic Mutation ◽  
Lung Tumors ◽  
Chemotherapeutic Agents ◽  
Signal Pathways ◽  
Lung Carcinogenesis

The incidence of lung adenocarcinoma has been remarkably increasing in recent years due to the introduction of filter cigarettes and secondary-hand smoking because the people are more exposed to higher amounts of nitrogen oxides, especially 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK), which is widely applied in animal model of lung tumors. In NNK-induced lung tumors, genetic mutation, chromosome instability, gene methylation, and activation of oncogenes have been found so as to disrupt the expression profiles of some proteins or enzymes in various cellular signal pathways. Transgenic animal with specific alteration of lung cancer-related molecules have also been introduced to clarify the molecular mechanisms of NNK in the pathogenesis and development of lung tumors. Based on these animal models, many antioxidant ingredients and antitumor chemotherapeutic agents have been proved to suppress the NNK-induced lung carcinogenesis. In the future, it is necessary to delineate the most potent biomarkers of NNK-induced lung tumorigenesis, and to develop efficient methods to fight against NNK-associated lung cancer using animal models.

scholarly journals miR-98-5p plays a critical role in depression and antidepressant effect of ketamine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chaoli Huang ◽  
Yuanyuan Wang ◽  
Zifeng Wu ◽  
Jiali Xu ◽  
Ling Zhou ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Social Stress ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Rapid Onset ◽  
Therapeutic Strategies ◽  
Antidepressant Effect ◽  
Depression Treatment ◽  
Chronic Social Stress ◽  
Beneficial Effects

AbstractKetamine has been demonstrated to be a rapid-onset and long-lasting antidepressant, but its underlying molecular mechanisms remain unclear. Recent studies have emerged microRNAs as important modulators for depression treatment. In this study, we report that miR-98-5p is downregulated in the prefrontal cortex and hippocampus of mice subjected to chronic social stress, while overexpressing it by its agonist alleviates depression-like behaviors. More importantly, we demonstrate that miR-98-5p is upregulated by ketamine administration, while inhibition of it by its antagonist blocks the antidepressant effect of ketamine. Our data implicate a novel molecular mechanism underlying the antidepressant effect of ketamine, and that therapeutic strategies targeting miR-98-5p could exert beneficial effects for depression treatment.

scholarly journals Genomic evidence of adaptive evolution in the reptilian SOCS gene family

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11677
Author(s):  
Tian Xia ◽  
Lei Zhang ◽  
Guolei Sun ◽  
Xiufeng Yang ◽  
Honghai Zhang
Keyword(s):  
Negative Selection ◽  
Molecular Mechanisms ◽  
Evolutionary Dynamics ◽  
Theoretical Foundation ◽  
Selective Pressure ◽  
Rapid Evolution ◽  
Cytokine Signaling ◽  
Signal Pathways ◽  
Branch Model ◽  
Comprehensive Study

The suppressor of the cytokine signaling (SOCS) family of proteins play an essential role in inhibiting cytokine receptor signaling by regulating immune signal pathways. Although SOCS gene functions have been examined extensively, no comprehensive study has been performed on this gene family’s molecular evolution in reptiles. In this study, we identified eight canonical SOCS genes using recently-published reptilian genomes. We used phylogenetic analysis to determine that the SOCS genes had highly conserved evolutionary dynamics that we classified into two types. We identified positive SOCS4 selection signals in whole reptile lineages and SOCS2 selection signals in the crocodilian lineage. Selective pressure analyses using the branch model and Z-test revealed that these genes were under different negative selection pressures compared to reptile lineages. We also concluded that the nature of selection pressure varies across different reptile lineages on SOCS3, and the crocodilian lineage has experienced rapid evolution. Our results may provide a theoretical foundation for further analyses of reptilian SOCS genes’ functional and molecular mechanisms, as well as their roles in reptile growth and development.

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