Regulatory role of CREB/BDNF signaling pathway in acute sleep deprivation-induced anxiety-like behavior mice

Objective:To investigate the regulatory role of cyclic adenosine monophosphate responsive element binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway in acute sleep deprivation(SD)-induced anxiety-like behavior mice(SD group)to study the mechanism of anxiety-like behavior better.Methods:The SD chamber was used to deprive the mice of sleep,and the anxiety-like behavior of the mice was verified using an open field test(OFT),elevated plus maze(EPM),forced swim test(FST),and tail suspension test(TST).Finally,proteins were detected by Western blotting.Result:OFT showed that the active distance and the time of stay in the central area were significantly reduced(P<0.05).EPM showed that the time and number of open arms in the SD group were significantly lower than in the control group(P<0.05).The FST showed that the forced swimming immobility time of the SD group was significantly lower than that of the control(P<0.05).Moreover,the TST showed that the immobility time of the tail suspension experiment in the SD group was significantly higher than that in the control group(P<0.05).Conclusion:Acute SD can regulate anxiety-like behavior in mice through the CREB/BDNF signaling pathway.

Effect of Chronic Administration of Cadmium on Anxiety-Like, Depression-Like and Memory Deficits in Male and Female Rats: Possible Involvement of Oxidative Stress Mechanism

The main objective of this work is to study the effect of chronic administration of cadmium (Cd) on the level of depression-like, anxiety-like, memory state and oxidative stress in male and female Wistar rats. For this purpose, this study was conducted with 24 rats for each gender. Four groups were constituted: (Group 1: Control): received saline solution NaCl (0.9%), (Group 2: Cd-0.25;Group 3: Cd-0.5;Group 4: Cd-1): received daily 0.25 mg/kg, 0.5 mg/kg and 1 mg/kg of Cd respectively during 8 weeks. After treatment period, animals were tested in the open-field, elevated plus maze tests for anxiety-like behavior, and forced swimming test for depression-like behavior. The Y maze was used to evaluate the working memory and the Morris Water Maze, to evaluate space learning and spatial memory. The results revealed that in males, all doses of Cd provoke depression-like, while in females only the group treated with 1 mg/kg Cd shows elevated depression-like behavior. In regard to anxiety-like behavior, Cd induces an anxiogenic effect in both genders tests. In the Y-Maze test, both males and females expressed a low percentage of alternations, suggesting that working memory was affected by Cd at 1 mg/kg. In the Morris Water Maze test, the space learning and spatial memory were significantly impaired in the group Cd-1. Neurochemical analysis showed that levels of nitric oxide and lipid peroxidation in the hippocampus were significantly increased after Cd treatments. Overall analysis of our data revealed that Cd caused significant alterations in the examined parameters that were sex-dependent and dose-dependent.

Effects of clonidine on anxiety-like behaviors of rats subjected to chronic hypoperfusional cerebral ischemia

Aim To investigate the effect of clonidine on anxiety-like behaviors of rats subjected to chronic hy- popeffusional cerebral ischemia. Methods Chronic hypopeffusional cerebral ischemia was established by perma- nent bilateral common carotid arteries occlusion （two-vessel occlusion, 2VO）. Three weeks after 2VO, rats were given clonidine （0.05 mg·kg^-1, i. p. ） for 14 days. Behavioural experiments including elevated plus maze （EPM） and open field test （OFT） were applied to evaluate anxiey-like behaviour after four-week ischemia. Re- suits 2VO rats significantly spent less time in open arm of EPM and more time in peripheral region of OFT com- pared with sham rats. Clonidine notably increased open arm time in EPM and prolonged time spent in center region in OFT of 2VO rats. Conlusion Chronic hypopeffusional cerebral ischemia caused anxiety-like behaviors of rats and clonidine showed an important role in improving anxiety-like behaviors in 2VO rats.

Effects of LW-AFC on anxiety-like behavior and immune function in corticosterone-induced mice

OBJECTIVE Chronic stress is one of the important factors in the development of many mental and neurological diseases,and cause damage to the central nervous system,affect animal emotions and damage the immune function of the body.The purpose of this study was to investigate the effects of LW-AFC which extracting from traditional Chinese medicine prescription Liuwei Dihuang decoctionon the anxiety-like behaviorand immune dysfunction abnormalities caused by chronic stress,and whether immune intervention affect the action of LW-AFC.METHODS Male BALB/c mice were subcutaneously injected with corticosterone(25 mg·kg^-1)for 28 d to establish a chronic stress model.Cyclophos⁃phamide(Cy,80 mg·kg^-1)was injected continuously for the initial three days,followed by once a week,LW-AFC(1.6 g·kg^-1)was given continuously for 28 d.Then investigate the emotion changes by open field and elevated plus maze tests,and detected the lymphocyte proliferation,lymphocyte subsets in peripheral blood,microglia and astrocyte expression,and inflammatory cytokines in peripheral blood and brain tissue.RESULTS The mice showed obvious depressive-like behaviorafter 28 d of continuous corticosterone injection.LW-AFC could significantly improve the anxietybehavior induced by corticosterone injection,but LW-AFC could not improve the anxietybehavior of mice by Cy intervention.The expression of glial cells in hippocampus of corticosterone-induced mice showed an upward trend,and the activation of microglia and astrocytes have significantly increase in corticosterone and Cy injected mice.LW-AFC significantly decreased the activation of microglia and astrocytes in corticosterone-induced mice with Cy intervention.This suggested that LW-AFC can reduce the damage of stress on the immune function of central nervous system under immunosuppres⁃sive state.Furthermore,LW-AFC could significantly up-regulate the proliferation of splenic lymphocyte stimulated by LPS and ConA,up-regulate the proportion of CD3+CD8+cells,reduce the proportion of CD4+/CD8+cells,decrease the secretion of inflammatory factors IL-6 and MCP-1 in plasma,and increase the level of anti-inflammatory factor IL-10 in plasma of mice induced by chronic corticosteroneinjection.While LW-AFC could promote the inflammatory factors TNF-α and IL-6in plasma,inhibit the secretion of anti-inflammatory factor IL-10 and inflammatory cytokine MCP-1 in hippocampus of corticosterone-induced mice with Cy intervention.CONCLUSION LW-AFC can improve anxiety-likebehavior induced by chronic stress,the Cy intervention affects the alleviation of anxiety-like behavior by LW-AFC as well as the regulation of immune function.The regulation of immune function might be the main way for LW-AFC to improve the function of central nervous system.

Exposure to Hypobaric Hypoxia and Reoxygenation Induces Transient Anxiety-Like Behavior in Rat

Chronic exposure to hypobaric hypoxia (HH) causes memory impairment and prolonged state of mental confusion. However, effect of high altitude exposure on mood state and its underlying mechanisms have been poorly studied.? Present study was undertaken to investigate the mood state alteration following chronic exposure to HH. Male Sprague Dawley rats were divided into five groups and exposed to hypoxia for 3, 7, 14 and 21 days in an animal decompression chamber at an altitude of 25,000ft. Anxiety-and depression-like behaviors were assessed by using various mazes along with changes in serotonin and glutamate level. Our study revealed a decrease in exploratory, grooming and rearing behavior in open field test following initial exposure to HH for 7 days without affecting the locomotory behavior. Initial exposure to HH-decreased time spent in open arm of elevated plus maze indicating induction of anxiety-like behavior which normalized on prolonged hypoxic exposure for 21 days. Hypoxic exposure for 7 days induced anhedonia and increased despair behavior in rat while there was steady improvement in these behaviors when exposed for 21 days. Decrease in serotonin level was noted in hippocampus along with elevated corticosterone and glutamate level which gradually decreased on prolonged exposure to HH. These findings suggest that initial exposure to HH increases transient anxiety-like behavior in rats followed by gradual improvement in mood state on prolonged exposure. Further, the study also indicates the involvement of serotonergic system in mood state alteration at high altitude following chronic exposure and reoxygenation.

Pyridoxal 5'-phosphate alleviates prenatal pyridaben exposureinduced anxiety-like behaviors in offspring

Pyridaben(PY)is a widely used organochlorine acaricide,which can be detected in the peripheral blood of pregnant women.Available evidence suggests that PY has reproductive toxicity.However,it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring.Here,we administered PY to pregnant mice at a dose of 0.5 and 5 mg kg^(-1)day^(-1)via gavage and observed anxietylike behaviors in PY offspring aged five weeks.We then integrated the metabolome and transcriptome of the offspring's brain to explore the underlying mechanism.Metabolome data indicated that the vitamin B6 metabolism pathway was significantly affected,and the pyridoxal 50-phosphate(PLP)concentration and the active form of vitamin B6 was significantly reduced.Moreover,the transcriptome data showed that both PLP generation-related Pdxk and anxiety-related Gad1 were significantly down-regulated.Meanwhile,there was a decreasing trend in the concentration of GABA in the hippocampal DG region.Next,we supplemented PLP at a dose of 20 mg kg^(-1)day^(-1)to the PY offspring via intraperitoneal injection at three weeks.We found up-regulated expression of Pdxk and Gad1 and restored anxiety-like behaviors.This study suggests that prenatal exposure to PY can disrupt vitamin B6 metabolism,reduce the concentration of PLP,down-regulate the expression levels of Pdxk and Gad1,inhibit the production of GABA,and ultimately lead to anxiety-like behaviors in offspring.

Changes in structural plasticity of hippocampal neurons in an animal model of multiple sclerosis

Structural plasticity is critical for the functional diversity of neurons in the brain.Experimental autoimmune encephalomyelitis(EAE)is the most commonly used model for multiple sclerosis(MS),successfully mimicking its key pathological features(inflammation,demyelination,axonal loss,and gliosis)and clinical symptoms(motor and non-motordysfunctions).Recentstudieshave demonstrated the importance of synaptic plasticity in EAE pathogenesis.In the present study,we investigated the features of behavioral alteration and hippocampal structural plasticity in EAE-affected mice in the early phase(11 days post-immunization,DPI)and chronic phase(28DPI).EAE-affected mice exhibited hippocampus-related behavioral dysfunction in the open field test during both early and chronic phases.Dendritic complexity was largely affected in the cornu ammonis 1(CA1)and CA3 apical and dentate gyrus(DG)subregions of the hippocampus during the chronic phase,while this effect was only noted in the CA1 apical subregion in the early phase.Moreover,dendritic spine density was reduced in the hippocampal CA1 and CA3 apical/basal and DG subregions in the early phase of EAE,but only reduced in the DG subregion during the chronic phase.Furthermore,mRNA levels of proinflammatory cytokines(Il1β,Tnfα,and Ifnγ)and glial cell markers(Gfap and Cd68)were significantly increased,whereas the expression of activity-regulated cytoskeletonassociated protein(ARC)was reduced during the chronic phase.Similarly,exposure to the aforementioned cytokines in primary cultures of hippocampal neurons reduced dendritic complexity and ARC expression.Primary cultures of hippocampal neurons also showed significantly reduced extracellular signal-regulated kinase(ERK)phosphorylation upon treatment with proinflammatory cytokines.Collectively,these results suggest that autoimmune neuroinflammation alters structural plasticity in the hippocampus,possibly through the ERK-ARC pathway,indicating that this alteration may be associated with hippocampal dysfunctions in EAE.

Effect of acetyl-L-carnitine on hypersensitivity in acute recurrent caerulein-induced pancreatitis and microglial activation along the brain’s pain circuitry

BACKGROUND Acute pancreatitis(AP)and recurring AP are serious health care problems causing excruciating pain and potentially lethal outcomes due to sepsis.The validated caerulein-(CAE)induced mouse model of acute/recurring AP produces secondary persistent hypersensitivity and anxiety-like behavioral changes for study.AIM To determine efficacy of acetyl-L-carnitine(ALC)to reduce pain-related behaviors and brain microglial activation along the pain circuitry in CAE-pancreatitis.METHODS Pancreatitis was induced with 6 hly intraperitoneal(i.p.)injections of CAE(50μg/kg),3 d a week for 6 wk in male C57BL/6J mice.Starting in week 4,mice received either vehicle or ALC until experiment’s end.Mechanical hypersensitivity was assessed with von Frey filaments.Heat hypersensitivity was determined with the hotplate test.Anxiety-like behavior was tested in week 6 using elevated plus maze and open field tests.Microglial activation in brain was quantified histologically by immunostaining for ionized calcium-binding adaptor molecule 1(Iba1).RESULTS Mice with CAE-induced pancreatitis had significantly reduced mechanical withdrawal thresholds and heat response latencies,indicating ongoing pain.Treatment with ALC attenuated inflammation-induced hypersensitivity,but hypersensitivity due to abdominal wall injury caused by repeated intraperitoneal injections persisted.Animals with pancreatitis displayed spontaneous anxiety-like behavior in the elevated plus maze compared to controls.Treatment with ALC resulted in increased numbers of rearing activity events,but time spent in“safety”was not changed.After all the abdominal injections,pancreata were translucent if excised at experiment’s end and opaque if excised on the subsequent day,indicative of spontaneous healing.Post mortem histopathological analysis performed on pancreas sections stained with Sirius Red and Fast Green identified wide-spread fibrosis and acinar cell atrophy in sections from mice with CAE-induced pancreatitis that was not rescued by treatment with ALC.Microglial Iba1 immunostaining was significantly increased in hippocampus,thalamus(intralaminar nuclei),hypothalamus,and amygdala of mice with CAE-induced pancreatitis compared to naïve controls but unchanged in the primary somatosensory cortex compared to naïves.CONCLUSION CAE-induced pancreatitis caused increased pain-related behaviors,pancreatic fibrosis,and brain microglial changes.ALC alleviated CAE-induced mechanical and heat hypersensitivity but not abdominal wall injury-induced hypersensitivity caused by the repeated injections.

Anxiolytic and free radical scavenging potential of Chinese celery(Apium graveolens) extract in mice

Objective: To elucidate the anxiolytic and free radical scavenging effect of methanolic extract of Apium graveolens(A. graveolens) in adult C57BL/6 mice.Methods: Sixty male mice were divided into 6 groups: control, vehicle, positive control and A. graveolens(125, 250 and 500 mg/kg). Different behavioral models of elevated plus maze, open field, light/dark, hole-board and pentobarbital-induced sleep were used to assess anxiety-like behavior. Biochemical parameters including monoamine oxidase-A(MAO-A) activity, lipid peroxidation, % inhibition of superoxide anion and glutathione peroxidase activity were measured. Histologic studies were also examined.Results: Mice receiving various doses of A. graveolens(125, 250 and 500 mg/kg)showed an alleviation of anxiety-like behavior as evidenced by the battery of behavioral tests. Likewise, A. graveolens treatment was found to significantly decrease MAO-A activity, lipid peroxidation as well as cause a significant increase of % inhibition of superoxide anion and glutathione peroxidase activity in both cortex and striatum. The total number of survival neurons found in the frontal cortex and striatum was significantly higher than that of the vehicle-treated group.Conclusions: Taken together, we showed that A. graveolens improve the behavioral changes which might be related to the inhibition of free radicals and modulation of MAOA activity resulting in an increased number of survival neurons. Our findings suggest the therapeutic potential of A. graveolens in the treatment of anxiety.

Affective Responses of Early Life Photoperiod in Male Wistar Rats

Behavior changes season dependant are probably linked to change in day length or photoperiod. Although much research on seasonality in small mammals has focused on photoperiod manipulations in adults, early life photoperiod is also an important source of seasonal information and can establish individual’s developmental trajectory by regulating somatic and reproductive development and affective responses to day lengths later in life. The experiments developed in this work are based on the hypothesis that early life photoperiod affect emotionality in adult rats. To cheek this hypothesis, male rats were exposed at birth to different photoperiods (LP: 16L/8D;SP: 8L/16D). 8, 16 or 24 weeks later, rats were subjected to different behavioral tests to quantify anxiety-like behavior. Independently of duration, rats exposed to SP exhibited higher levels of anxious-like behavior than rats raised in LP, in an open field test (OFT) and in elevated plus maze (EPM). Repeated comparisons showed that photoperiod effect was accentuated after 16 weeks of treatment. 24 weeks of treatment failed to induce any effect on emotionality in male rats. Our results indicate that changes in day length are associated with different levels of anxious-like behaviors;consistent with the conjecture that early life photoperiod may influence affective behavior in adult male rats.

Restraint Induces Sickness Responses Independent of Injection with Epstein-Barr Virus (EBV)-Encoded dUTPase

Most adult humans have been infected by Epstein-Barr virus (EBV), a putative cause of chronic fatigue syndrome, and carry latent EBV. The EBV-encoded dUTPase can induce sickness responses in mice and chronic stress exacerbates this response. Because individuals often adapt to chronic stress, we tested the hypothesis that acute restraint stress would potentiate these sickness responses elicited by EBV-encoded dUTPase. Male CD-1 mice were injected daily for one or three days with either saline or EBV-encoded dUTPase. Additionally, mice from each condition were either restrained for three hours daily or left undisturbed during the light phase when mice are inactive. Restraint decreased weight gain during the one- and three-day experiments. Restraint in saline injected mice increased anxiety-like behavior in the open field during the three-day experiment. There were no behavioral differences during the one-day experiment. Restraint stress had no effect when experienced acutely on one day, but did produce a sickness response after three days of exposure regardless of saline or dUTPase injection. In contrast to the effects of chronic stress and EBV-encoded dUTPase on the sickness response, acute stress did not affect sickness responses in association with EBV-encoded dUTPase. Thus, dUTPase does not appear to provoke the same sickness responses after acute stress as compared to chronic stress.

Affective Behavior Dysregulation Was Induced by Chronic Administration of Copper in Wistar Rats

As both deficiency and excess of copper (Cu) can be harmful, dysregulation in its homeostasis has been connected with various neurological disorders. The present study was undertaken to examine whether Cu chronic administration can induce alterations of affective behavior especially anxiety and depression levels in male and female rats. Twenty-four rats, for each gender, divided in control and three test groups (n = 6), were injected intraperitoneally with saline (0.9% NaCl) or CuCl2 (0.25 mg/kg, 0.5 mg/kg and 1 mg/kg) for 8 weeks. After treatment period, animals were tested in the open-field, elevated plus maze tests for anxiety-like behavior, and forced swimming test for depression-like behavior. Results demonstrated that Cu administered chronically, exerts an anxiogenic effect in rats. In the OFT, Cu decreases the TCA and NRC parameters without modifying the locomotor activity represented by the NTS parameter. With regard to EPM, Cu decreases TOA and EOA parameters without modifying the TAE parameter. A significant increase in depression-like symptoms was also exhibited by Cu treated rats (p 2 showed maximum anxiety-like and depression-like symptoms as compared to controls as well as from the other two doses indicating dose-dependent effects of chronic Cu administration. Overall, these results suggest that intoxication with Cu has potentially deleterious effects on brain as reflected in behavioral dysfunctions such as depression and anxiety.

S4A-2 Role of Trace Amine-Associated Receptor 1(TAAR 1)in Nicotine Addiction

Background and Purpose:Nicotine addiction and abuse remains a global health issue.To date,the fundamental neurobiological mechanism of nicotine addiction remains incompletely understood.Trace amine-associated receptor 1(TAAR1)is thought to directly modulate dopaminergic system and are thought to be a neural substrate underlying addictivelike behaviors.We aimed to investigate the role of TAAR1 in nicotine addictive-like behaviors.Experimental Approach:TAAR1 expression after nicotine treatment was evaluated by western blotting.c-Fos immunofluorescence and in vivo fast-scan cyclic voltammetry were used to examine the activation of brain regions and dopamine release,respectively.We then thoroughly and systematically examined the role of TAAR1 in mediating nicotine-induced sensitization,nicotine discrimination,nicotine self-administration,nicotine demand curve,and the reinstatement of nicotine-seeking.Local pharmacological manipulation was conducted to determine the role of TAAR1 in the nucleus accumbens(NAcs)in the reinstatement of nicotine-seeking.Minipump was implanted into TAAR 1 knockout mice and their wildtype counterparts to establish physical dependence.One week after the minipump implantation,the pump was retrieved and mecamylamine was used to precipitate physical withdrawal signs including observable signs and anxiety-like behaviors(elevated plus maze).Key Results:We found that the expression of TAAR1 protein was selectively downregulated in the NAc,with no change in either dorsal striatum or prefrontal cortex.TAAR1 activation was sufficient to block nicotine-induced c-Fos expression in the NAc,while also reducing nicotine-induced dopamine release in the NAc.Systemic administration of TAAR1 agonists attenuated the expression and development of nicotine-induced sensitization,nicotine self-administration,the reinstatement of nicotine-seeking,and increased the elasticity of nicotine demand curve,while intra-NAc infusions of a TAAR1 agonist was sufficient to attenuate nicotine reinstatement.Moreover,TAAR1-knockout rats showed augmented cue-induced and druginduced reinstatement of nicotine-seeking.Mice that were physically dependent on chronic nicotine exposure demonstrated significant withdrawal signs after mecamylamine treatment,and TAAR 1 knockout mice demonstrated more severe withdrawal signs.TAAR 1 agonist reduced the withdrawal signs in the wildtype mice.Conclusions and Implications:These results indicated that modulation of TAAR1 activity regulates nicotine addictive-like behaviors and TAAR1 represents a novel target towards the treatment of nicotine addiction.

Methyl Donors Supplementation Attenuates the Adverse Effects of Maternal High Fructose Diet of Offspring Emotional and Cognitive Behaviors

Free Fatty acid is an end-product of hepatic metabolism of fructose. Most of past studies have demonstrated significant relationship between gestational high fat diet and metabolic and physiology outcomes in offspring. However, there is a scarce of data extended to the effects of high fructose diet-fed dams on juveniles’ progeny. Therefore, the present experiment was designed to examine the later effects of maternal high fructose diet intake during pregnancy and lactation on juvenile offspring rats emotional behaviors and memory abilities. We tested whether methyl donors supplemented to that high fructose diet could reverse the adverse effects. We found at two months of age, anxiety-like behavior and depression-like behavior were elevated in off springs of mother fed to high fructose diet and a sex difference effect with males were more affected than females. In addition, behavioral outcomes indicated that the high fructose diet also impaired spatial working and recognition memories in the Y-maze and object recognition test respectively. Blood glucose intolerance increased significantly in juvenile males rats of dams fed with high fructose diet when compared to females. However, a supplementation of the maternal diet with methyl donors attenuated all these changes. Our study suggested a controlled fructose diet supplemented to methyl donors during critical period of brain developing (in utero and pre-weaning stage), otherwise that could induced irreversible detrimental effects on offspring behavior and cognitive health.

电针对创伤后应激障碍大鼠行为学及海马SYN、PSD95表达的影响

Objective: Electroacupuncture (EA) in the treating principle of “soothing the liver and regulating the kidney” was applied to intervion the rats with post-traumatic stress disorder (PTSD), and its effect on anxiety-like behavior, spatial learning and memory ability, and expressions of synaptophysin (SYN) and postsynaptic dense 95 (PSD95) in hippocampus of rats were observed to explore the underlying mechanism.Methods: Twenty-four male SD rats were randomly divided into control group, model group, and EA group, with 8 rats in each group. There was no intervention in the control group. The rest 16 rats were prepared for modeling. The single-prolonged stress & shock (SPS&S) method was used to establish the PTSD models. There was no intervention in the model group after modeling. In the EA group, “Bǎihuì (百会GV20)”“ Shéntíng (神庭GV24)”“Gānshū (肝俞BL18)”“Shènshū (肾俞BL23)” were manipulated with EA stimulation, intensity 1 mA, frequency 2/100 Hz, disperse-dense wave, and treatment was performed once a day, 20 min each time, for a total of 21 days. Open field test, elevated plus maze and Morris water maze tests were used to observe the behavioral differences of rats in each group. Immunohistochemical method was used to observe the differences of positive expressions of proteins SYN and PSD95 in hippocampus.Results: In the open field test, compared with the control group, the total traveling distance, the percentage of the time spent in the central cell and the numbers of the central cells crossing in the model group were all decreased (all P < 0.05). Compared with the model group, these indicators in the EA group were significantly all increased (all P < 0.05). In the elevated plus maze test, compared with the control group, the percentages of open arm staying time and entering times in the model group were both decreased (both P < 0.05). Compared with the model group, these indicators in the EA group were both significantly increased (both P < 0.05). The results of Morris water maze test showed that compared with the control group, the escape latency time and travelled distance of rats in the model group were all increased from day1 to day 4 (all P < 0.05), and the percentage of staying time in the target quadrant was decreased (P < 0.05). Compared with the model group, the escape latency time and travelled distance of EA group were both significantly shortened (both P < 0.05), and the percentage of staying time in the target quadrant was significantly increased (P < 0.05). The immunohistochemical results showed that, compared with the control group, the positive expressions of SYN and PSD95 in the hippocampus of the model group were significantly down-regulated (both P < 0.05). Compared with the model group, the positive expressions of SYN and PSD95 in the hippocampus of the EA group were significantly up-regulated (both P < 0.05).Conclusions: EA in the treating principle of “soothing the liver and regulating the kidney” can effectively relieve anxiety-like behavior and improve spatial learning and memory ability of rats with PTSD, and the mechanism is related to the up-regulation of the expressions of SYN and PSD95 in the hippocampus.

Does acupuncture response increase with the increasing dosage:A preclinical study investigating rats with sleep deprivation

Background:The effectiveness of acupuncture for insomnia and insomnia-related anxiety and depression has been widely investigated in clinical trials.However,whether higher dosage(more frequent)acupuncture can bring greater responses(a greater size of effect)is less understood.Objective:This study is designed to investigate whether a five-times weekly(5 Ts/w)electroacupuncture(EA)treatment is better than a three-times weekly(3 Ts/w)EA in alleviating sleep deprivation,and sleep disturbance-induced cognitive dysfunctions and negative emotions in rats through four various behavioral te sts.Methods:Forty-six male Sprague-Dawley rats were randomly divided into control group(n=10),model group(n=12),EA-3 Ts/w group(n=12),and EA-5 Ts/w group(n=12).Except for the control group,the other three groups were established as chronic sleep deprivation models via the modified multi-platform water environment methodology.Then,rats in both EA-3 Ts/w group and EA-5 Ts/w group received corresponding dosage of EA therapy,respectively.After modeling and interventions,all four groups received four behavioral tests as follows:(1)sleep behavioral monitoring and evaluation was achieved by Comprehensive Lab Animal Monitoring System(CLAMS).(2)Cognitive functions were assessed by Novel Object Recognition(NOR)test.(3)Depressive-like behaviors was evaluated by Open-Field(OF)test.(4)Anxietylike behaviors was appraised by Elevated Plus-Maze(EPM)test.After finishing the behavioral tests,the hippocampus of each rat was removed and its synaptic structure changes were observed under electron microscope.Results:(1)CLAMS:two EA groups derived more sleep time within 24 h than the model group(both P<0.05),and no statistical differences was found between these two EA groups(P>0.05).(2)NOR test:NOR ratio in the EA-3 Ts/w group was higher than that of the model group(P<0.05)but lower than that of either the control group(P<0.05)or the EA-5 Ts/w group(P<0.05).(3)OF test:the difference of horizontal movements between the EA-3 Ts/w group and the EA-5 Ts/w group was not significant(P>0.05),although both of them were lower than that of the control group(both P<0.05)but higher than that of the model group(P<0.05).(4)EPM test:no significant decline of open-arm total time(OT)was found in EA-3 Ts/w group(P>0.05)but was found in both the model group(P<0.05)and the EA-5 Ts/w group(P<0.05)compared to the control group.Conclusion:(1)Five-week EA treatment can partially mitigate cognitive dysfunctions,anxiety-like behaviors,and depressive behaviors in rats with sleep deprivation,and this effect might be associated with the repairs on mitochondrial damage in hippocampal neurons.(2)There is insufficient evidence supporting 3 Ts/w EA treatment is less effective than 5 Ts/w EA treatment in mitigating sleep deprivation symptoms and depressive behaviors induced by sleep deprivation among rats.(3)5 Ts/w EA treatment might be more effective than 3 Ts/w EA treatment in attenuating sleep deprivation-induced cognitive impairments while it might further increase rat’s anxiety-like behaviors at the same time.