下丘脑NK2受体在应激介导抑郁症发生中的作用

目的 阐明神经激肽A的受体NK2在慢性不可预见性温和刺激(CUMS)所致的抑郁样行为发生、发展中的可能作用和机制.方法 SD大鼠随机分为对照组、氟西汀组和抑郁模型组3组,行为学检测后,氟西汀组和抑郁模型组均给予孤养+CUMS造成大鼠抑郁症模型,再次行为学检测后,氟西汀组大鼠给予氟西汀腹腔注射21d,抑郁模型组给予同体积生理盐水腹腔注射21d,再次进行行为学检测,麻醉后取大鼠下丘脑,提取组织mRNA和蛋白后,采用荧光定量PCR技术和Western Blot技术检测NK2的表达.结果 应激前3组大鼠的糖水偏好率和强迫游泳的不动时间均无统计学意义.应激后,氟西汀组和抑郁模型组大鼠的糖水摄入明显减少、强迫游泳不动时间明显增长,差异均有统计学意义(P＜0.05).而给予氟西汀后,氟西汀组大鼠的糖水偏好率有所增加,强迫游泳的不动时间有所减少,与对照组比较差异无统计学意义(P＞0.05),但与抑郁组大鼠相比,差异均有统计学意义(P＜0.05).与对照组和氟西汀组比较,抑郁组下丘脑NK2受体的mRNA和蛋白的表达量明显升高,差异有统计学意义(P＜0.05),而氟西汀组与对照组相比差异无统计学意义(P＞0.05).结论 CUMS可引起大鼠行为学改变,造成大鼠抑郁模型;NK2受体的mRNA和蛋白的表达量在应激后大鼠的下丘脑中明显升高,经氟西汀干预后可恢复到正常水平,说明NK2受体与抑郁症的发生、发展过程具有相关性,在抑郁症的发病机制中可能发挥重要作用.     

氟西汀对DISC1转基因小鼠应激后抑郁和焦虑样 行为的影响

目的 探讨氟西汀对双重应激诱导的精神分裂症断裂基因1（DISC1）转基因小鼠抑郁和焦 虑样行为的影响。方法 C57BL/6野生型新生小鼠及C57BL/6 LBD-DISC1转基因新生小鼠各16只，分别 随机分为野生应激组、野生对照组和DISC1应激组、DISC1对照组，每组8只。应激组小鼠进行母婴分离 和慢性不可预知轻度应激后，4组小鼠使用氟西汀治疗4周，采用糖水消耗实验、强迫游泳实验及旷场实 验测定小鼠行为。结果 氟西汀治疗后各组小鼠旷场实验中心区域移动距离和强迫游泳静止时间之间 的差异无统计学意义，DISC1应激组的糖水偏好度和体重仍偏低（P＜ 0.01）。结论 氟西汀可改善双重应 激诱导的DISC1转基因小鼠的抑郁和焦虑情绪，但不能缓解其快感缺乏和体重降低。     

Vanillin吸嗅对抑郁模型SD大鼠血清Mg~(2+)的影响

目的探讨嗅质香兰素(Vanillin)吸嗅对SD大鼠抑郁样行为的调节作用及可能的作用机制。方法雄性SD大鼠70只,采用CUMS+孤养或嗅球毁损,制备抑郁样模型,符合模型大鼠随机分为Vanillin吸嗅组、氟西汀组、模型组、嗅球毁损+Vanillin吸嗅组及假手术组。评价大鼠干预后各时间点的神经行为学变化及血清Mg2+含量。结果 (Vanillin吸嗅组干预2w后强迫游泳实验时间明显缩短(P<0.05);24h糖水消耗量实验明显增加(P<0.05);5w后旷野实验自主活动次数增加(P<0.05);血清Mg2+含量明显提高(P<0.05)。结论 Vanillin吸嗅可以缓解抑郁模型大鼠的抑郁样行为,其机制可能是提高血清Mg2+含量,通过Mg2+调控HPA轴,影响海马、杏仁核情绪中枢活动,从而达到防治抑郁症的作用。     

circRIMS2靶向miR-186调控BDNF表达减轻CRS诱发的小鼠抑郁样行为

目的 探讨抑郁样行为小鼠体内中 circRIMS2 变化及 circRIMS2 对糖氧剥夺（OGD）诱导 HT22 细胞凋亡的影响。方法 （1）将 45 只 C57BL/6 雌性小鼠随机分为对照组、模型组与氟西汀组,每 组 15 只。通过慢性束缚应激（CRS）对模型组和氟西汀组小鼠构建抑郁样行为模型,对氟西汀组小鼠 给予 10 mg/kg 的氟西汀治疗。采用糖水偏好测试、悬尾测试、强迫游泳测试和开野测试评估小鼠抑郁 样行为。评估后取小鼠血清和大脑海马组织,采用逆转录实时定量聚合酶链式反应（RT-qPCR）检测环 状 RNA、miR-186 及 BDNF mRNA 的表达水平。采用 Western blot 法检测小鼠海马组织中 BDNF 蛋白表 达情况。（2）在 HT22 细胞中分别加入慢病毒载体 pLO-circCon、pLO-circRIMS2 转染试剂后,取一部分 HT22 细胞进行 OGD 处理以构建体外凋亡模型。根据进行过的细胞转染和 OGD 操作,将 HT22 细胞分为 Control+pLO-circCon 组、Control+pLO-circRIMS2 组、OGD+pLO-circCon 组和 OGD+pLO-circRIMS2 组。采 用 RT-qPCR 检测 4 组细胞中 circRIMS2、miR-186 及 BDNF mRNA 的表达水平,通过流式细胞术检测并计 算 4 组细胞凋亡率。采用 Western blot 法检测细胞中 BDNF 蛋白表达情况。结果 （1）与对照组相比,模 型组小鼠糖水偏好率低,悬尾与强迫游泳不动时间长,开野测试得分低,血清中 circTRAM2、circTNIK 与 circTFRC 表达水平高,circDOCK4、circRIMS2,circSTAG1 表达水平低,差异均有统计学意义（均P＜ 0.01）。与模型组相比,氟西汀组小鼠糖水偏好率高,悬尾与强迫游泳不动时间短,开野测试得分高, 血清中 circRIMS2 表达水平高,差异均有统计学意义（均P＜ 0.01）。（2）与 Control+pLO-circCon 组相比, Control+pLO-circRIMS2 组细胞中 circRIMS2、BDNF mRNA 表达水平高,miR-186 表达水平和细胞凋亡 率低,差异均有统计学意义（均P＜ 0.01）。与 OGD+pLO-circCon 组相比,OGD+pLO-circRIMS2 组细胞中 circRIMS2、BDNF mRNA 表达水平高,miR-186 表达水平和细胞凋亡率低,差异均有统计学意义（均P＜ 0.01）。结论 circRIMS2 基因与小鼠抑郁样行为存在关联,抑郁样行为小鼠血清中 circRIMS2 表达降低, 氟西汀治疗能提高 circRIMS2 表达。慢病毒质粒提高细胞中 circRIMS2 基因表达,能通过 miR-186/BDNF 信号减轻 OGD 诱发的神经元凋亡。     

香兰素吸嗅对大鼠抑郁样行为及脑单胺类神经递质的影响

目的研究香兰素吸嗅对大鼠抑郁样行为改善及其机制。方法慢性不可预见性中等强度应激(CUMS)+孤养的方法建立大鼠抑郁症模型。为验证香兰素作用途径,另设立大鼠嗅球毁损(OBX)模型。于造模前、后及干预后4 w测试大鼠糖水消耗量和强迫游泳不动时间,干预结束后超高压液相色谱检测大鼠脑内5-HT、DA、NE的量。结果与造模后相比,CUMS+香兰素吸嗅组大鼠神经行为学指标显著好转(P<0.05);其脑匀浆液5-HT、DA的量显著高于空白对照组(P<0.05)。与造模后相比OBX+香兰素吸嗅组大鼠神经行为学指标未见好转(P>0.05);其脑匀浆液5-HT、DA、NE均显著低于假手术组(P<0.05)。结论香兰素可经嗅觉通路改善大鼠抑郁样行为,其机制可能通过提升脑内5-HT、DA实现的。     

维生素D治疗抑郁症的增效作用

目的 比较帕罗西汀联合维生素D与帕罗西汀联合安慰剂治疗抑郁症的效果.方法 将50例抑郁症患者随机分成两组,研究组25例给予帕罗西汀联合维生素D,对照组25例给予帕罗西汀和安慰剂,进行为期8周的双盲安慰剂对照的随机分组研究.采用24项汉密尔顿抑郁量表(HAMD)和不良反应量表(TESS)评定临床疗效和不良反应,以电化学发光法测定受试者基础血清维生素D水平.结果 共有48例受试完成试验.治疗8周后,研究组和对照组患者的显效率分别为87.5％(21/24)和75.0％(18/24),差异有统计学意义(X2＝10.71,P＜0.05).治疗后6周和8周时,研究组HAMD评分明显低于对照组,两组间比较差异有统计学意义(P＜0.05).两组TESS评分比较差异无统计学意义(P＞0.05).结论 维生素D能增强帕罗西汀治疗抑郁症的效果.     

补骨脂素抗抑郁作用及机制研究

目的 研究补骨脂素的抗抑郁作用及机制。方法 采用大鼠强迫游泳、小鼠强迫游泳及 小鼠悬尾3 种抑郁模型，将动物随机分为对照组、补骨脂素低剂量组、补骨脂素高剂量组、阿米替林组， 观察各组药物对大/ 小鼠强迫游泳不动时间和悬尾不动时间的影响；同时在细胞水平建立皮质酮损伤 PC12 细胞模型，观察补骨脂素的细胞保护作用。结果 在大/ 小鼠强迫游泳和小鼠悬尾实验中，补骨 脂素可显著缩短大/ 小鼠的强迫游泳不动时间和悬尾不动时间，与对照组比较差异均有统计学意义 （P＜ 0.05）；皮质酮损伤PC12 细胞模型中，补骨脂素显著提高 PC12 细胞的存活率，拮抗皮质酮诱导的细 胞损伤作用。结论 补骨脂素具有抗抑郁效应，其机制可能与神经细胞保护作用相关。     

帕罗西汀联合小剂量舒必利对女性抑郁症疗效及安全性的影响

目的 探讨帕罗西汀联合小剂量舒必利静滴治疗女性抑郁症患者的临床疗效和安全性.方法 将62例女性抑郁症患者随机分为两组,研究组给予帕罗西汀合并舒必利静滴治疗,对照组则仅给予帕罗西汀治疗,疗程为8周,仅在疗程前2周合并舒必利静滴治疗.采用汉密尔顿抑郁量表(HAMD)评定临床疗效,不良反应症状量表(TESS)评定不良反应情况.结果 治疗8周末两组HAMD评分下降,差异有统计学意义(P＜0.01),显效率差异无统计学意义(P＞0.05),但研究组起效较快;两组TESS评分差异无统计学意义(P＞0.05),不良反应均较轻微.结论 帕罗西汀联合小剂量舒必利静滴治疗女性抑郁症起效快,安全性高.     

TLR4信号对睡眠剥夺诱导小鼠抑郁症中的作用

目的 探究TLR4蛋白对长期异相睡眠剥夺(PSD)诱导抑郁样行为小鼠脑组织中炎症反应的影响。方法 45只小鼠随机分为对照(Control)组、模型(Model)组与NLRP3抑制剂(TAK242)组。取Model与TAK242组小鼠,将小鼠放置在水上平台剥夺异相睡眠期,连续5d,期间TAK242组小鼠连续腹腔注射10 mg·kg^-1 TAK242溶液。取各组小鼠开展糖水偏好测试、悬尾测试、强迫游泳测试与社交互动测试,取小鼠脑脊液检测炎性细胞因子释放,取全脑组织进行免疫荧光染色,取海马体开展PCR定量分析与Western blotting。结果 与Control组相比,Model组小鼠糖水摄取率明显减少,强迫游泳、悬尾不动时间增加,社交互动时间减少(P<0.05)。此外,Model组小鼠TLR4 mRNA水平,Iba1荧光表达,炎性细胞因子含量,p-NF-κB与NLRP3表达明显增加(P<0.05)。与Model组相比,TAK242组小鼠糖水摄取率明显增加,强迫游泳、悬尾不动时间减少,且社交互动时间增加(P<0.05)。此外,TAK242组小鼠TL...     

电针对慢性不可预知温和应激小鼠模型抑郁样行为及肠道菌群的调节作用

目的 观察电针对慢性不可预知温和应激（CUMS）模型小鼠抑郁样行为及肠道菌群组 成的影响。方法 将 40 只雄性 C57BL/6 小鼠随机分为对照组、电针组、模型组（CUMS 组）和治疗组 （CUMS+ 电针组）,每组 10 只。CUMS 组和 CUMS+ 电针组均接受 CUMS 造模,造模结束后,给予对照组和 CUMS 组小鼠假刺激 7 d,给予电针组和 CUMS+ 电针组小鼠 2/15 Hz、1.0 mA 的电针刺激 7 d。最后一次 干预结束 24 h 后,收集粪便保存在 -80℃条件下并对小鼠进行糖水偏好实验、旷场实验和强迫游泳实 验。对 4 组小鼠的粪便进行 16S rDNA 测序,采用操作分类单元（OTU）信息进行 α 多样性和 β 多样性 分析、线性判别分析效应量分析（LEfSe）。采用 Spearman 相关性分析小鼠行为学指标与差异菌群富集 水平之间的相关性。结果 CUMS 组小鼠的旷场中心区域探索时间短于对照组［（22.058±4.148）s 比 （37.864±4.407）s］,糖水偏好率低于对照组［（53.427±14.550）% 比（76.514±15.701）%］,强迫游泳不动 时间长于对照组［（82.599±32.369）s 比（47.606±15.344）s］,差异有统计学意义（P＜ 0.01）。CUMS+ 电针 组小鼠的旷场中心区域探索时间长于 CUMS 组［（30.604±6.060）s 比（22.058±4.148）s］,糖水偏好率高于 CUMS组［（72.731±13.933）%比（53.427±14.550）%］,强迫游泳不动时间短于CUMS组［（53.633±17.933）s 比（82.599±32.369）s］,差异有统计学意义（P＜ 0.05）。CUMS 组小鼠肠道菌群的 OTU 数量、ACE 指数和 Chao 指数低于对照组,差异有统计学意义（P＜ 0.05）;但 CUMS+ 电针组与 CUMS 组比较,差异无统计学 意义（P＞ 0.05）。Ruminococcaceae_UCG_002 属、蓝绿藻菌属（Lachnoclostridium）和 Rikenellaceae_RC9_ gut_group 属在 CUMS 组中富集,且与抑郁样行为呈正相关（P＜ 0.05）;放线菌门和理研菌属、杜氏杆菌属、 Ileibacterium 属、双歧杆菌属和异杆菌属在电针和 CUMS+ 电针组中富集,且均与抑郁样行为呈负相关 （P＜ 0.05）。结论 电针干预可以缓解小鼠的抑郁样行为,且对其肠道菌群组成有调节作用。     

Development of the projection from the nucleus of the brachium of the inferior colliculus to the superior colliculus in the ferret

Neurons in the deeper layers of the superior colliculus (SC) have spatially tuned receptive fields that are arranged to form a map of auditory space. The spatial tuning of these neurons emerges gradually in an experience-dependent manner after the onset of hearing, but the relative contributions of peripheral and central factors in this process of maturation are unknown. We have studied the postnatal development of the projection to the ferret SC from the nucleus of the brachium of the inferior colliculus (nBIC), its main source of auditory input, to determine whether the emergence of auditory map topography can be attributed to anatomical rewiring of this projection. The pattern of retrograde labeling produced by injections of fluorescent microspheres in the SC on postnatal day (P) 0 and just after the age of hearing onset (P29), showed that the nBIC-SC projection is topographically organized in the rostrocaudal axis, along which sound azimuth is represented, from birth. Injections of biotinylated dextran amine-fluorescein into the nBIC at different ages (P30, 60, and 90) labeled axons with numerous terminals and en passant boutons throughout the deeper layers of the SC. This labeling covered the entire mediolateral extent of the SC, but, in keeping with the pattern of retrograde labeling following microsphere injections in the SC, was more restricted rostrocaudally. No systematic changes were observed with age. The stability of the nBIC-SC projection over this period suggests that developmental changes in auditory spatial tuning involve other processes, rather than a gross refinement of the projection from the nBIC.     

Mechanisms of the suppression of the nociceptive reflex of the opening of the mouth during stimulation of the structures of the limbic brain

The comparative effectiveness of the inhibitory influence of tetanic stimulation of hypothalamus, amygdala and limbic cortex on EMG-response of m. digastricus evoked by electrical stimulation of tooth pulp nociceptive afferents was studied in cats anesthetized with a mixture of chloralose and nembutal. It was found that inhibition of the EMG-component of the jaw-opening reflex is most pronounced in case of stimulation of medial and lateral region of the hypothalamus, the inhibitory effect of central and medial nuclei of the amygdala is less pronounced and the effect of the limbic cortex is the weakest. It was shown that the mechanism of the antinociceptive effect of tetanic stimulation of the hypothalamus is not related to the concomitant increase of the blood pressure. After stabilization of the blood pressure the suppressive effect of the hypothalamus remains without changes, that points out to a direct, primary, not baro-afferent mechanism of the inhibition of the activity of nociceptive neurons of the trigeminal sensory nuclei. Noradrenaline, injected intravenously, induced a large increase of the blood pressure accompanied by a pronounced inhibition of the pain reflex. Angiotensin causes the same degree of blood pressure elevation without changes in the amplitude of the EMG-response of the pain reflex. Hypothalamic and noradrenergic mechanisms for control of pain sensitivity are discussed.     

The organization of the connections between the cortex and the claustrum in the monkey

The distribution of labelled cells and of extracellular granules in the claustrum has been studied after injections of horseradish peroxidase in several areas of the neocortex. The frontal and parietal lobes are related to the anterior and posterior halves respectively of the claustrum, and the occipital and temporal cortex to the posterior and inferior margins. Parts of the claustrum related to areas of the cortex in the frontal lobe overlap considerably in the antero-posterior dimension with parts related to widely separated but interconnected areas of the parieto-temporal cortex. Areas of cortex within one lobe which are interconnected are related to parts of the claustrum which overlap in the dorsoventral dimension.     

Investigating the construct validity of the SPAI-C: comparing the sensitivity and specificity of the SPAI-C and the SAS-A

Investigates the construct validity of the Social Phobia and Anxiety Inventory for Children (SPAI-C) by comparing its sensitivity and specificity with another self-report measure of social anxiety, the Social Anxiety Scale for Adolescents (SAS-A). Participants were 252 adolescents (124 males and 128 females) 13-17 years old. Adolescents completed the SPAI-C and the SAS-A and were interviewed using the Anxiety Disorders Interview Schedule for DSM-IV: Child Version (ADIS-IV:C). Parents were also interviewed and composite diagnoses were formed. Youth were classified as socially phobic or non-anxious based on these composite diagnoses. By comparing clinical cutoff scores with diagnostic group classification, the sensitivity and the specificity of the SPAI-C and SAS-A were compared. Results indicated that the SPAI-C was a more sensitive measure than the SAS-A (61.5% vs. 43.6%) providing evidence of the scale's construct validity. The two measures were similar with regard to specificity (82.7% for both). Implications of these results for assessment and research are discussed.