突触后密度家族蛋白与疼痛研究进展

PSD是最早在电镜下发现的位于突触后膜的"致密物蛋白质".这种"致密物"是由一系列细胞骨架蛋白结合了多种与突触信号传递相关的分子(包括受体和各种激酶等)构成的特殊结构.其中一些成员,包括NMDA受体、CaMKII、PSD-93及PSD-95,与疼痛的发生、维持及治疗密切相关,并且彼此之间有着"微妙"的相互调节作用.     

Targeting neuronal nitric oxide synthase as a valuable strategy for the therapy of neurological disorders

The management of neurological disorders have huge and increasing human and economic costs. De-spite this, there is a scarcity of effective therapeutics, and there is an extreme urgency for new and real treatments. In this short review we analyze some promising advancements in the search of new bioactive molecules targeting neuronal nitric oxide synthase (nNOS), an enzyme deputed to the biosynthesis of nitric oxide (NO). In different conditions of neuronal damages, this molecule is overproduced, contribut-ing to the pathogenesis and progression of neuronal diseases. Two main approaches to modulate nNOS are discussed: a ifrst one consisting in the direct inhibition of the enzyme by means of small organic molecules, which can be also active against other different targets involved in such diseases. A second section is dedi-cated to molecules able to prevent the formation of the ternary complex N-methyl-D-aspartate (NMDA)-type glutamate receptors, postsynaptic density-95 (PSD95) protein-nNOS, which is necessary to activate the latter for the biosynthesis of NO.     

电针治疗中风后抑郁145例

目的验证电针治疗中风后抑郁的有效性及安全性,探究其作用机制。方法 300例PSD患者随机分为电针组150例给予电针治疗,1次/d,15 d为1个疗程;药物组给予氟西汀口服治疗;两组均连续治疗5 W。治疗前后进行汉密顿抑郁量表（HAMD）积分判定和血清白细胞介素-6（IL-6）、肿瘤坏死因子α（TNFα）和可溶性白细胞介素-2受体（SL-2R）的含量测定。结果电针组HAMD积分显著低于药物组（p〈0.05）,疗效优于药物组（p〈0.05）,血IL-6（p〈0.05）和SL-2R（p〈0.05）含量显著低于药物组,副反应低于药物组（p〈0.01）。结论电针治疗有助于减轻PSD病情,疗效显著、安全,能降低PSD患者血清IL-6、SL-2R含量。降低PSD患者血清中部分细胞因子水平,纠正紊乱的免疫功能可能是电针治疗PSD的作用机制之一。     

卒中后抑郁特点及舍曲林治疗临床效果分析

目的研究卒中后抑郁(PSD)的特点,观察抗抑郁剂舍曲林对卒中后抑郁患者神经功能康复的影响,为卒中后抑郁的干预提供依据。方法采用临床流行病学调查方法对198例脑卒中患者进行卒中后抑郁及其相关因素的现状调查,将PSD患者随机分为舍曲林治疗组和对照组,观察舍曲林对患者神经功能康复的疗效。结果卒中后抑郁的发生率为36.86%,卒中后抑郁的特点为睡眠障碍、绝望、运动阻滞和焦虑等主要表现;卒中后抑郁患者HAMD和ADI评分高;口服舍曲后治疗组与对照组相比HAMD、HDL、NFDS减分明显,抗抑郁治疗在缓解抑郁症状的同时,可以改善患者日常生活能力和神经功能缺损。结论卒中后抑郁发生率较高,以睡眠障碍、绝望、运动阻滞和焦虑等为主要表现,抗抑郁剂舍曲林不仅可以明显改善卒中后抑郁的抑郁症状,还能提高患者的日常生活能力,促进患者神经功能的康复。     

脑卒中后抑郁与脑损伤部位关系的临床研究

目的:探讨脑卒中后抑郁(PSD)与脑卒中病变部位之间的关系.方法:对175例脑卒中患者进行汉密尔顿抑郁量表(HAMD)评分,神经功能缺损评分,对发生卒中后抑郁的患者进行脑内病变部位的相关分析.结果:73例脑卒中患者合并PSD,总发生率41.71%,其中轻度抑郁22.29%,中度抑郁12.57%,重度抑郁6.85%;PSD发生与卒中类型无关,而与病变部位、神经功能缺损程度等因素有关.结论:PSD发生率高,脑器质性损伤的部位可能是其发生的生物学基础;神经功能缺损程度评分越高,其患抑郁的程度也就越高.     

Plasma and cerebrospinal fluid substance P in post-stroke patients with depression

Aims: To investigate the correlation between the incidence of post‐stroke depression (PSD) and the levels of substance P (SP) in the plasma and cerebrospinal fluid (CSF). Methods: Ninety‐one stroke patients were divided into PSD (n = 46) and post‐stroke (without depression) groups (n = 45). PSD must have occurred 2–4 weeks after the onset of the stroke and was determined by the Hamilton Rating Scale for Depression (HAMD). In addition, the subjects were divided into anterior (n = 67) and posterior circulation stroke groups (n = 24) based on the location of the focus as determined by computed tomography. All recruited patients were graded by the National Institutes of Health Stroke Scale (NIHSS). Results: The results included the following findings: (i) the level of plasma SP in the PSD group (58.47 ± 14.39) was higher than that of the PS group (36.98 ± 9.49; P = 0.000), while the level of CSF SP in the PSD group (72.13 ± 13.06) was higher than that of the post‐stroke group (37.30 ± 12.57; P = 0.03); (ii) the level of plasma SP was positively correlated with the HAMD and NIHSS score; (iii) the level of plasma SP (38.45 ± 12.23), the HAMD score (9.08 ± 8.72), and the NIHSS score (3.25 ± 1.90) of the anterior stroke group (51.21 ± 16.27, 17.46 ± 15.96, and 6.91 ± 3.30, respectively) were higher than those of the posterior stroke group (38.45 ± 12.23, 9.08 ± 8.7, and 3.25 ± 1.90, respectively; P = 0.017, P = 0.001, and P = 0.000, respectively). Conclusions: SP in the plasma and CSF of patients exhibited a close correlation with neural damage and the incidence of PSD. This study also suggested that anterior hemispheric strokes may play a significant role in development of PSD.     

Influence of chronic cocaine treatment and sleep deprivation on sexual behavior and neurogenesis of the male rat

The present study investigated the influence of chronic cocaine treatment on genital reflexes associated with paradoxical sleep deprivation (PSD), and possible alterations in hippocampus neurogenesis of the male rat. At 21 days of age, the rats were distributed into two groups and injected with saline or cocaine (7 mg/kg, three times a week for 12 weeks). At age 90 days, they were submitted to a four-day period of PSD (PSD groups) or maintained in home-cages (control groups), challenged with saline or cocaine administration, and placed in observation cages to assess genital reflexes. Two additional groups were used to quantify neurogenesis. PSD rats treated chronically with cocaine and challenged with saline did not differ from their respective control groups. The association of PSD with cocaine potentiated penile erection (PE) when compared to PSD-saline (saline challenged) rats, and these effects were similar to those observed in long-term cocaine treated rats. The bromodeoxyuridine (BrdU) assay indicated a reduction in BrdU-positive cells in the adult hippocampus after chronic cocaine treatment. These findings show that long-term cocaine treatment from brain development through adulthood had a marked effect on sexual responses and neuronal proliferation.     

Sleep rebound attenuates context-dependent behavioural sensitization induced by amphetamine

We have recently demonstrated that paradoxical sleep deprivation (PSD) potentiates the induction of amphetamine (AMPH)-induced behavioural sensitization by increasing its conditioned component. In the present study, the effects of sleep rebound (induced by 24 h recovery period from PSD) were studied on AMPH-induced behavioural sensitization. Sleep rebound attenuated the acute locomotor-stimulating effect of AMPH. AMPH-induced behavioural sensitization was context-specific and was also attenuated by sleep rebound. These results strengthen the notion that sleep conditions can influence AMPH-induced behavioural sensitization.