Bi Hu

Rapid eye movement sleep deprivation selectively impairs recall of fear extinction in hippocampus-independent tasks in rats.

Previous studies have shown that rapid eye movement (REM) sleep deprivation (RSD) exerts a detrimental effect on some memory tasks. However, whether post-learning RSD impairs memory for fear extinction, an important model of inhibitory learning, remains to be elucidated. The present study examined the effects of post-extinction RSD from 0 to 6 h and 6 to 12 h on recall of fear extinction tested 24 h after extinction training. We found that RSD from 0 to 6 h significantly increased freezing when recall of extinction of cued fear was tested in the context in which rats received extinction training whereas RSD from 6 to 12 h had no effect (experiments 1 and 2, two hippocampus-independent memory tasks). RSD at either time point had no effect on freezing when recall of extinction of cued fear was tested in the context different from that in which extinction training occurred (experiment 3, a hippocampus-dependent memory task). Additionally, we observed no effect of RSD at either time point on freezing during recall test for extinction of contextual fear (experiment 4, a hippocampus-dependent memory task). These results suggest that the effects of post-extinction RSD on memory for fear extinction are complex. RSD impairs recall of fear extinction in hippocampus-independent tasks, but does not affect recall of fear extinction in hippocampus-dependent tasks. Our findings extend previous research on the effects of RSD on learning and memory and support the notion that REM sleep is involved in memory process of certain tasks.

MiRNA-21 reverses high glucose and high insulin induced insulin resistance in 3T3-L1 adipocytes through targeting phosphatase and tensin homologue.

AIMS/HYPOTHESIS Our previous study showed there was a change of microRNA (miRNA) expression profile, and miR-21 was significantly down regulated in insulin-resistant adipocytes (IR-adipocytes). Phosphatase and tensin homologs deleted on chromosome 10 (PTEN), a negative regulator of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, was identified to be a target gene of miR-21, which suggested miR-21 might be associated with insulin resistance (IR) or diabetes. However, it is not known whether miR-21 play any role in the development of IR in 3T3-L1 adipocytes. METHODS Normal adipocytes and adipocytes transfected with pre-miR-21(pmiR-21) or negative control (pNeg) were treated with high glucose and high insulin for 24 h, insulin-stimulated glucose uptake was determined by 2-Deoxyglucose transport assay, miR-21 expression level was measured by using quantitative real-time RT-PCR (qRT-PCR). The protein expression levels of PTEN, Akt, phospho-Akt (Ser473), IRβ, GSK3β, phospho-GSK3β (Ser9) and GLUT4 were detected by western blotting assay. RESULTS We further confirmed that miR-21 was down regulated in IR-adipocytes by qRT-PCR. Over-expression of miR-21 significantly increased insulin-induced glucose uptake and decreased PTEN protein expression, while it had no significant effect on PTEN mRNA expression in IR-adipocytes. Moreover, over-expressing miR-21 significantly increased insulin-induced phosphorylation of AKT (Ser473), GSK3β (Ser9) and the translocation of glucose transporter 4 (GLUT4) in IR-adipocytes. CONCLUSIONS In this study, our data demonstrate that miR-21 reverses high glucose and high insulin induced IR in 3T3-L1 adipocytes, possibly through modulating the PTEN-AKT pathway, and miR-21 may be a new therapeutic target for metabolic diseases such as T2DM and obesity.

Chronic morphine selectively impairs cued fear extinction in rats: implications for anxiety disorders associated with opiate use.

Previous studies have shown that opioid transmission plays an important role in learning and memory. However, little is known about the course of opiate-associated learning and memory deficits after cessation of chronic opiate use in a behavioral animal model. In the present study, we examined the effects of chronic morphine on fear extinction, an important preclinical model for behavior therapy of human anxiety disorders. Rats were administrated subcutaneously morphine hydrochloride or saline twice per day for continuous 10 days. Rats received a cued or contextual fear conditioning session 7 days after the last morphine injection. During subsequent days, rats received four cued or contextual extinction sessions (one session per day). Percent freezing was assessed during all phases of training. Chronic morphine did not affect the acquisition of cued fear response or the initial encoding of extinction memory within each session, but produced an impairment in the between-session extinction. However, the same morphine treatment schedule did not affect the acquisition or extinction of contextual fear response. These results suggest that the effects of chronic morphine on memory for fear extinction are complex. Chronic morphine selectively impairs extinction of cued fear response. This deficit in fear extinction may be one of those critical components that contribute to the high prevalence of anxiety disorders in opiate addicts.

The physiological and pathophysiological roles of adipocyte miRNAs

MicroRNAs (miRNAs) are highly conserved, small, noncoding RNAs that regulate gene expression at the posttranscriptional level. Their actions affect numerous important biological processes, including adipocyte differentiation and function, sugar and lipid metabolism, and insulin production and secretion. Recent reports suggest miRNAs may also be involved in the pathogenic processes of obesity, diabetes, and insulin resistance. In this review, we summarize research progresses on adipocyte miRNAs and their physiological and pathological implications.

Arecoline improves vascular endothelial function in high fructose-fed rats via increasing cystathionine-γ-lyase expression and activating K ATP channels

Aim:To investigate the effect of arecoline, a major component of betel nut, on vascular endothelial function in high fructose-fed rats and the potential mechanisms underlying the effect.Methods:Male Wistar rats were fed a high-fructose or control diet for 16 weeks. At the beginning of week 13, the rats were injected ip with low (0.5 mg·kg−1·d−1), medium (1.0 mg·kg−1·d−1) or high (5.0 mg·kg−1·d−1) doses of arecoline for 4 weeks. At the termination of the treatments, blood was collected, fasting blood glucose (FBG) and serum insulin (FSI) levels were measured, and insulin sensitivity index (ISI) was calculated. The thoracic aortas were isolated and aortic rings were prepared for studying ACh-induced endothelium-dependent vasorelaxation (EDVR). The mRNA and protein expression of cystathionine-γ-lyase (CSE) in the thoracic aortas was analyzed using RT-PCR and Western blot analysis, respectively.Results:In high fructose-fed rats, the levels of FBG and FSI were remarkably increased, whereas the ISI and the mRNA and protein expression of CSE were significantly decreased. ACh-induced EDVR in the aortic rings from high fructose-fed rats was remarkably reduced. These changes were reversed by treatment with high dose arecoline. Pretreatment of the aortic rings rings from high fructose-fed rats with the CSE inhibitor propargylglycine (10 mmol/L) or the ATP-sensitive potassium (KATP) channel blocker glibenclamide (10 mmol/L) abolished the restoration of ACh-induced EDVR by high dose arecoline. On the contrary, treatment with high dose arecoline significantly impaired ACh-induced EDVR in the aortic rings from control rats, and pretreatment with propargylglycine or glibenclamide did not cause further changes.Conclusion:Arecoline treatment improves ACh-induced EDVR in high fructose-fed rats, and the potential mechanism of action might be associated with increase of CSE expression and activation of KATP channels by arecoline.

Assessing functioning of the prefrontal cortical subregions with auditory evoked potentials in sleep–wake cycle

Our previously observations showed that the amplitude of cortical evoked potentials to irrelevant auditory stimulus (probe) recorded from several different cerebral areas was differentially modulated by brain states. At present study, we simultaneously recorded auditory evoked potentials (AEPs) from the dorsolateral prefrontal cortex (DLPFC) and the ventromedial prefrontal cortex (VMPFC) in the freely moving rhesus monkey to investigate state-dependent changes of the AEPs in the two subregions of prefrontal cortex. AEPs obtained during passive wakefulness (PW), active wakefulness (AW), slow wave sleep (SWS) and rapid-eye-movement sleep (REM) were compared. Results showed that AEPs from two subregions of prefrontal cortex were modulated by brain states. Moreover, a significantly greater increase of the peak-to-peak amplitude (PPA) of N1-P1 complexes appears in the DLPFC during PW compared to that during AW. During REM, the PPA of N1-P1 complexes presents a contrary change in the two subregions with significant difference: a significant increase in the DLPFC and a slight decrease in the VMPFC compared to that during AW. These results indicate that the modulation of brain states on AEPs from two subregions of the prefrontal cortex investigated is also not uniform, which suggests that different subregions of the prefrontal cortex have differential functional contributions during sleep-wake cycle.

Retraction Note to: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

Organophosphate-induced delayed neuropathy (OPIDN) is pathologically characterized by the swollen axon containing aggregations of microtubules, neurofilaments, smooth endoplasmic reticulum and multivesicular vesicles. At present, the exact mechanism of OPIDN is unclear and the effective therapeutic methods is not available to counter this syndrome. Recent studies had shown that the autophagy was involved in OPIDN. The adipocytokine Apelin is a peptide, Apelin and its receptor are abundantly expressed in the nervous system. Recent researches illuminated that Apelin was neuroprotective factor and Apelin could regulate the autophagy in vivo and vitro model. So we investigated the effect of Apelin-13 on the OPIDN induced by Tri-ortho-cresyl phosphate (TOCP) in hens and explored the role of autophagy in Apelin-13 preventing OPIDN. Adult Roman hens were given a single dose of 750 mg/kg TOCP by gavage for 21 days to induce OPIDN, and neural dysfunction were detected, and the formation of autophagosomes in spinal cord neurons was observed by transmission electron microscopy, and the molecular markers of autophagy microtubule-associated protein light chain-3 (LC3) and the autophagy substrates p62/SQSTM1 were determined by Western blot analysis. The results demonstrated that the obvious neurological dysfunction such as hindlimb paralysis and paralysis of gait was present, the number of autophagosomes in the neurons of spinal cords was significantly increased, the level of LC3-II and p62 expressions and the ratio of LC3-II/LC3-I in spinal cords and sciatic nerve were significantly increased in the OPIDN model group compared with the control group. Compared with the OPIDN model group, the neurological dysfunction of tens was obviously reduced, the clinical signs scores was significantly decreased, the number of autophagosomes in the neurons of hen spinal cords was significantly decreased, the level of LC3-II and p62 expressions and the ratio of LC3-II/LC3-I in spinal cords and sciatic nerve were significantly decreased in Apelin-13 treatment group. Our results suggested that Apelin-13 prevented against the OPIDN induced by TOCP in hens, which the mechanism might be associated with regulation autophagy flux by Apelin-13.