Natural reversal of mandibular condylar cartilage histological damage caused by chronic unpredictable moderate stress in rats / 口腔疾病防治

Objective @#To investigate the histological damage recovery of temporomandibular joint condylar cartilage caused by chronic unpredictable moderate stress, aiming to provide an experimental basis for the prevention and treatment of temporomandibular disorder.@*Methods @#This animal experiment was approved by the Laboratory Animal Ethical Inspection, School of Stomatology, The Fourth Military Medical University (No. 2020081). 60 male SD rats were randomly divided into control group, stress group, and 2-, 4- and 8-week post-stress recovery groups. Rats were subjected to chronic unpredictable moderate stress (CUMS) for 8 weeks including damp sawdust for 24 hours, tilted cage for 12 hours, noise for 4 hours, light/dark cycle reversal, water immersion, tail clamp, and restraint stress. The serum assessment, behavioral tests, histological and ultrastructural observation were performed 2-, 4- and 8-weeks after stress factors were removed. Serum levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were determined with ELISA. The sucrose preference test (SPT) and the forced swim test (FST) were used to assess the depressive-like behavior. The expression level of interleukin-1α (IL-1α) and matrix metalloproteinases-3 (MMP-3) were determined by Immunohistochemistry and Western blot.@*Results @#At the end of 8 weeks of CUMS, the serum levels of CORT and ACTH were significantly higher in stress group compared with control group (P<0.01). The sucrose preference decreased significantly and the immobility time increased significantly in the stressed rats compared with those in the control group, indicating a successful establishment of CUMS. The condylar cartilage showed significant degenerative changes, with disorganized collagen fibers and reduced proteoglycan synthesis on the cartilage surface. IL-1α and MMP-3 were expressed in the intracellular and extracellular matrix of the condylar cartilage, and their expression levels were increased (P<0.01). After 2 weeks of stress removal, the serum levels of CORT and ACTH were decreased but higher than control group (P<0.01), and behavioral changes were still different from the control group (P<0.01); the loosened collagen fibers could still be seen on the surface of condylar cartilage, and some free cell areas were visible within the proliferative layer; additionally, IL-1α and MMP-3 expression in the condyle was reduced in all layers of cartilage when compared with the stress group, but was still higher than in the control group (P<0.01). After 4 weeks of stress removal, the serum levels of CORT and ACTH changes returned to normal levels and behavioral changes were still different from control group (P<0.05); a few collagen fibers could be seen on the surface of the condylar cartilage and the expressions of IL-1α and MMP-3 decreased significantly compared with the stress group (P<0.01), with the similar level of IL-1α (P>0.05) and higher expression of MMP-3 comparing with the control group (P<0.01). After 8 weeks of stress removal, behavioral changes returned to normal levels, with no statistically significant differences compared with the control group (P>0.05). The condylar collagen fibers increased and showed a corrugated pattern, and no serious subchondral bone damage as well as irreversible damage occurred. Both of the expression levels of IL-1α and MMP-3 approached those of the control group after 8 weeks of stress removal (P>0.05). @*Conclusion@# The behavioral changes and condylar cartilage damage caused by CUMS could be self-repaired. The decline in IL-1α and MMP-3 expression may be one of the intrinsic mechanisms of this self-repair process.

The role of dopamine D3 receptor in perimenopausal depression / 西安交通大学学报(医学版)

【Objective】 To investigate the role of dopamine D3 receptor deficiency in depression-like behavior in perimenopausal depression and to explore the role of dopamine D3 receptor in the pathogenesis of perimenopausal depression. 【Methods】 Based on the perimenopausal depression animal model， RT-PCR was used to study the changes of D3 receptor mRNA in the nucleus accumbens （NAc） in mice. Furthermore， dopamine D3 receptor knockout （D3RKO） mice and wild type （WT） mice of the same genetic background were used， respectively. Forced swim test （FST） and tail suspension test （TST） were used to assess depressive-like behavior in mice. 【Results】 D3 receptor mRNA in the NAc decreased significantly in perimenopause （P0.05）. 【Conclusion】 Dopamine D3 receptor in the NAc is significantly decreased during perimenopause. Obvious decrease or deficiency of dopamine D3 receptors may be involved in the regulation of perimenopausal depression.

Research progress of melanin concentrating hormone on depression / 中国药理学通报

Melanin-concentrating hormone (MCH) is an essential neuromodulator involved with multiple neurophysiological functions,such as feeding, mood and sleep-wake cycle. In recent years, the effects of melanin concentrating hormone on depression have attracted much attention, gradually becoming a highlight of developing advanced antidepressants. This article focuses on the research progress of MCHergic system and depression, looking forward to its future research direction.

Effects of voluntary wheel running exercise on depressive-like behavior and circadian rhythmic alterations of neuroendocrine induced by chronic unpredictable mild stress in rats / 中国病理生理杂志

AIM:To investigate the effect of 8-week middle intensity voluntary wheeling exercise on the de-pressive-like behavior and the circadian rhythmic alterations of plasma hormone and peptide induced by chronic unpredicta -ble mild stress (CUMS) in rats.METHODS: Male Sprague-Dawley rats (n =90) were randomly divided into model group, model+exercise group and control group .Rats in model+exercise group received 8-week voluntary wheel running exercise plus CUMS procedure during the last 3 weeks at the same time .Exploratory locomotor activity was assessed by open field test, the anxiety-like behavior was measured by elevated plus-maze test, and lack of pleasure was detected by su-crose preference test.Blood samples were collected at each of 6 time points (ZT1, 5, 9, 13, 17 and 21 on the 2nd day af-ter behavior testing ) .Plasma concentrations of corticosterone ( CORT) , melatonin ( MT) and vasoactive intestinal peptide ( VIP) were detected by ELISA .The plasma concentration of adrenocorticotropic hormone ( ACTH) was measured by ra-dioimmunoassay .The circadian rhythm changes of serum CORT , MT, VIP and ACTH concentrations in each group were compared by cosinor analysis .RESULTS:Compared with control group , locomotor activity , weight gain and sucrose con-sumption in model group were significantly reduced ( P<0.01 ) .The values of the percentage of open-arm time ( OT%) and open arm entries ( OE%) were obviously lower in model group than those in control group ( P<0.01 ) .Eight-week voluntary wheel running exercise may improve the above depression behavior caused by CUMS .The rats in model group showed an obvious disorder in circadian rhythm of plasma ACTH and CORT , including phase advance and decrease in am-plitude.There also showed a markedly blunted circadian rhythm and decreased level of plasma MT in model rats compared to control rats.VIP expression was significantly higher than that in control group with 24 h rhythm, but the amplitude was significantly lower than that in control group , peak phase also delayed for 6 h.Eight-week exercise significantly ameliorated the abnormal expression and the disturbance secretion rhythm of ACTH , CORT, MT and VIP in plasma .CONCLUSION:Eight-week voluntary wheeling exercise ameliorates CUMS-induced depressive-like behaviors probably by rescuing the dis-turbed circadian rhythms and abnormal secretion of these neuroendocrine factors .

Effects of voluntary wheel running exercise on depressive-like behavior and circadian rhythmic alterations of neuroendocrine induced by chronic unpredictable mild stress in rats / 中国病理生理杂志

AIM:To investigate the effect of 8-week middle intensity voluntary wheeling exercise on the de-pressive-like behavior and the circadian rhythmic alterations of plasma hormone and peptide induced by chronic unpredicta -ble mild stress (CUMS) in rats.METHODS: Male Sprague-Dawley rats (n =90) were randomly divided into model group, model+exercise group and control group .Rats in model+exercise group received 8-week voluntary wheel running exercise plus CUMS procedure during the last 3 weeks at the same time .Exploratory locomotor activity was assessed by open field test, the anxiety-like behavior was measured by elevated plus-maze test, and lack of pleasure was detected by su-crose preference test.Blood samples were collected at each of 6 time points (ZT1, 5, 9, 13, 17 and 21 on the 2nd day af-ter behavior testing ) .Plasma concentrations of corticosterone ( CORT) , melatonin ( MT) and vasoactive intestinal peptide ( VIP) were detected by ELISA .The plasma concentration of adrenocorticotropic hormone ( ACTH) was measured by ra-dioimmunoassay .The circadian rhythm changes of serum CORT , MT, VIP and ACTH concentrations in each group were compared by cosinor analysis .RESULTS:Compared with control group , locomotor activity , weight gain and sucrose con-sumption in model group were significantly reduced ( P<0.01 ) .The values of the percentage of open-arm time ( OT%) and open arm entries ( OE%) were obviously lower in model group than those in control group ( P<0.01 ) .Eight-week voluntary wheel running exercise may improve the above depression behavior caused by CUMS .The rats in model group showed an obvious disorder in circadian rhythm of plasma ACTH and CORT , including phase advance and decrease in am-plitude.There also showed a markedly blunted circadian rhythm and decreased level of plasma MT in model rats compared to control rats.VIP expression was significantly higher than that in control group with 24 h rhythm, but the amplitude was significantly lower than that in control group , peak phase also delayed for 6 h.Eight-week exercise significantly ameliorated the abnormal expression and the disturbance secretion rhythm of ACTH , CORT, MT and VIP in plasma .CONCLUSION:Eight-week voluntary wheeling exercise ameliorates CUMS-induced depressive-like behaviors probably by rescuing the dis-turbed circadian rhythms and abnormal secretion of these neuroendocrine factors .

The effects of high-fat diet during pregnancy and lactation on the behaviors and learning memory in adult male offspring / 中华行为医学与脑科学杂志

Objective To investigate the effects of high-fat feeding during pregnancy and lactation on the behaviors and learning memory in adult male offspring,as well as explore its possible mechanisms.Methods Female SD rats were exposed to either high fat diet (HF) or normal diet (ND) during pregnancy and lactation period.From weaning,all male offspring were fed with ND until 120-day.The offspring whose mothers were fed with HF or ND received 14 d chronic unpredictable mild stress (CUMS) or normal circumstance,and being divided into ND group,ND+CUMS group,HF group and HF+CUMS group(9 rats in each group).The Open-field test,sucrose preference test and forced swimming test were used to evaluate the depressive-like behaviors,and Morris water maze test was employed to assess the learning and memory ability.Moreover,blood samples were taken via chronically implanted cardiac catheters for measurement of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels in another set of DN group and HF group with normal circumstance during baseline and restraint stress (1 h).Results (1) Compared with the ND group,the sucrose preference in the HF group were decreased (P＜0.05).Compared with ND group,ND +CUMS group showed more serious depressive-like behavior.Vertical score in open-field test (11.36±8.25) and sucrose preference(0.63±0.04) of HF+CUMS group,were lower than those of the ND+CUMS group ((17.12±7.54),(0.73±0.05),respectively).The immobility time in forced swimming test of HF+CUMS group ((33.16±6.35)s) were longer than that of ND+CUMS group ((25.74±7.31) s).(2) In Morris water maze test,the crossing platform times of the HF group was less than those of the HF group.Compared with ND+CUMS group,the target quadrant time,effective area residence time and crossing platform times of HF+CUMS group were decreased significantly (P＜0.05).(3)There was no differences in basal ACTH and CORT between ND group and HF group (P＞0.05).Both ND group and HF group exhibited significantly elevated levels of plasma ACHT and CORT during restraint,but without significant difference between these two groups (P＞ 0.05).Within 3 h after restraint,the HF group showed significant increase of ACTH and CORT compared with ND group(P＜0.05).Conclusion As one kind of distress in early life,high-fat geeding through pregnancy and lactation increase the susceptibility and severity of depressive-like behaviors in adult offspring,as well as reducing the learning and memory ability,and the activity of hypothalamic-pituitary-adrenal axis activity during stress may contribute to the changes.

Potential Mechanisms Underlying the Facilitation of Fear Memory Extinction by Cotinine.

Posttraumatic stress disorder is a type of anxiety disorder that manifests after exposure to a traumatic event that was perceived as life threatening. Individuals with posttraumatic stress disorder have a deficiency in the extinction of fear memory. Moreover, environmental cues similar to the ones present during the trauma induced abnormal symptoms of fear and anxiety. Current therapies only help a small percentage of patients with this condition, thus pharmacological interventions to reduce the conditioned fear response are needed. Nicotine and its main metabolite, cotinine, have been shown to help in the extinction of fear memories in animal models. In this article we will discuss potential mechanisms and brain regions that may be underlying the effect of cotinine in enhancing the extinction of fear response after fear conditioning. The relevance of these mechanisms in posttraumatic stress disorder is discussed.