Sensory nociceptive axons invade the cerebellum of transgenic mice overexpressing nerve growth factor

Transgenic mice possessing elevated levels of mRNA expression and synthesis for the neurotrophin nerve growth factor among astrocytes display a robust ingrowth of new sympathetic fibers to the cerebellum. In this investigation, we report that the cerebellum of these mice also possesses a dense plexus of aberrant axons of sensory origin. Axons stained immunohistochemically for calcitonin gene-related peptide were seen in the transgenic cerebellum as early as one week after birth. The density of these axons dramatically increased with age. Immunopositive axons were confined predominantly to the deep white matter of the cerebellum in the adult transgenic mice, with a smaller number of axons seen coursing along blood vessels in the gray matter. Axons stained immunohistochemically for the neurotrophin receptor, p75^NTR, displayed a similar pattern of distribution and density as those immunostained for calcitonin gene-related peptide. Wild-type post-natal and adult animals lacked such calcitonin gene-related peptide- and p75^NTR-immunoreactive axons in the cerebellum. Retrograde labelling revealed that these axons within the transgenic cerebellum originated from neurons in the sensory trigeminal and dorsal root ganglia (upper cervical levels). This investigation demonstrates that overexpression of nerve growth factor is capable of inducing the directional growth of collateral axons of sensory neurons into the undamaged mammalian central nervous system.     

Induction of nerve growth factor mRNA in a rat dorsal root ganglion after application of a tourniquet

We investigated the mRNA levels of neurotrophins and neurotrophin receptors in a rat dorsal root ganglion (DRG), after tourniquet application to a hind limb, to identify the nerve-protective molecules that are induced immediately after peripheral nerve crush and play a part in the process leading to secondary events. No significant expression of nerve growth factor (NGF) mRNA or protein was observed in the control or contralateral DRG. NGF mRNA expression started within 2 h and NGF protein expression was observed in Schwann cells at 4 h after application of the tourniquet, due to termination of the neurotrophin supply from peripheral nerves. The levels of neurotrophin 3 mRNA were significantly increased in the DRGs on both sides at 1 and 2 h after tourniquet application, but no significant changes in brain-derived neurotrophic factor and neurotrophin 4/5 expression levels were observed in either the contralateral or ipsilateral DRG. The expression levels of neurotrophin receptors in the DRGs on both the contralateral and ipsilateral sides had decreased at 1 to 2 h after application of the tourniquet and had returned to the control levels at 4 h after tourniquet application.     

Regulation of cell survival in the developing thalamus: an in vitro analysis

There is evidence that developing thalamic cells become dependent for their survival on the integrity of their afferent and/or efferent connections, which may provide required levels of neural activity and/or essential neurotrophic factors. These connections develop in the second half of gestation in mice and, during this time (embryonic days 17-19), isolated thalamic cells either grown as explants or dissociated from each other lose their ability to survive. Here we show that the loss of viability of explants, but not of dissociated cells, is delayed if the cultures are treated with depolarizing stimuli. The survival of dissociated thalamic cells is promoted by culture medium conditioned by thalamic explants grown with depolarizing stimuli, indicating that the effect of depolarization involves trophic factors released by thalamic cells. This survival promoting effect is found prenatally, but not postnatally, and is prevented by the neurotrophin blocker K252a. Culture medium conditioned by cortex also promotes the survival of thalamic cells and this effect does occur postnatally. These findings suggest that diffusible factors, possibly members of the neurotrophin family, and depolarizing stimuli regulate thalamic cell survival before birth, but trophic support from cortex becomes crucial after birth. This culture model may provide a means of investigating the mechanisms of thalamic cell survival during development.     

Neurotrophic properties of olfactory ensheathing glia

Olfactory ensheathing cells (OEC) constitute a specialized population of glia that accompany primary olfactory axons and have been reported to facilitate axonal regeneration after spinal cord injury in vivo. In the present report we describe OEC neurotrophic factor expression and neurotrophic properties of OECs in vitro. Investigation of the rat olfactory system during development and adulthood by radioactive in situ hybridization revealed positive labeling in the olfactory nerve layer for the neurotrophic molecules S-100beta, CNTF, BMP-7/OP-1, and artemin, as well as for the neurotrophic factor receptors RET and TrkC. Ribonuclease protection assay of cultured OEC revealed expression of NGF, BDNF, GDNF, and CNTF mRNA, while NT3 and NT4 mRNA were not detectable. In vitro bioassays of neurotrophic activity involved coculturing of adult OEC with embryonic chick ganglia and demonstrated increased neurite outgrowth from sympathetic, ciliary, and Remak's ganglia. However, when culturing the ganglia with OEC-conditioned medium, neurite outgrowth was not stimulated to any detectable extent. Our results suggest that the neurotrophic properties of OEC may involve secretion of neurotrophic molecules but that cellular interactions are crucial.     

神经营养素-3基因启动区多态与精神分裂症的连锁不平衡研究

目的 探讨神经营养素－３（ｎｅｕｒｏｔｒｏｐｈｉｎ－３,ＮＴ－３）基因启动区二核苷酸重复多态与精神分裂症之间的关系。方法 对１１５个精神分裂症患者家系「其中同胞家系（１０５个）及核心家系（１０个）」进行基因分型,并结合诊断、阳性与阴性症状量表（ＰＡＮＳＳ）４个分量表的评分及发病年龄进行多等位基因模型和二等位基因模型的连锁不平衡分析。结果 （１）在多等位基因模型的连锁不平稳分析中,全体家系及发病年龄     

The impact of environmental enrichment in laboratory rats--behavioural and neurochemical aspects

The provision of environmental enrichment (EE) for laboratory rats is recommended in European guidelines governing laboratory animal welfare. It is believed the EE implementation can improve animals’ well-being and EE has been used to demonstrate learning and plasticity of the brain in response to the environment. This review suggests that the definition and duration of EE varies considerably across laboratories. Notwithstanding this, some EE protocols have revealed profound effects on brain neurochemistry and resulting behaviour, suggesting that EE can have the potential to significantly modify these parameters in rats. For this review, a literature search was conducted using PubMed and the search terms “Environmental Enrichment” and “rats”. From the results of this search the most important variables for consideration in the implementation of EE are identified and summarised, and include cage size and housing density; rat age, sex and strain; duration of EE; the EE protocol and enrichment items employed; and the use of appropriate controls. The effects of EE in a number of behavioural tests and its effects on neurotransmitters, neurotrophic factors, stress hormones and neurogenesis and proliferation are outlined. The findings summarised in the present review show the range of EE protocols employed and their effects in tests of activity, learning and affect, as well neurochemical effects which mediate enhanced plasticity in the brain. EE, as is provided in many laboratories, may be of benefit to the animals, however it is important that future work aims to provide a better understanding of EE effects on research outcomes.     

儿童期难治性癫痫的治疗进展

如何合理应用抗癫痫药物治疗儿童期难治疗癫痫以获得满意的治疗效果,已经引起广大医务工作者的广泛注意。新型抗癫痫药的问世和应用,给儿童癫痫患者的治疗带来了希望和更多的选择。虽然没有证据显示新型抗癫痫药比传统抗癫痫药更有效,但许多研究已经证明它们的抗痫谱广,药物相互作用和不良反应少,耐受性和安全性较传统抗癫痫药好。神经营养因子、抗氧化剂既有脑保护作用,又有抗癫痫作用。迷走神经刺激术、脑电刺激术、冷却法、放射疗法等物理疗法为难治性癫痫的治疗拓宽新的思路。改良后的生酮饮食疗法的临床实用性值得进一步研究。     

Brain-derived neurotrophic factor plasma levels in patients suffering from post-traumatic stress disorder

In both animals and humans, stress has been demonstrated to reduce the expression of the Brain-Derived Neurotrophic Factor (BDNF), a neurotrophin (NT) which promotes the proliferation, survival and differentiation of neurons. Although traumatic events have been found to be associated with lower BDNF plasma levels in affective disorders, no study has explored this parameter in patients with post-traumatic stress disorder (PTSD). We, therefore, measured BDNF plasma level in 18 patients with PTSD and in 18 healthy control subjects. Diagnoses were assessed by the Structured Clinical Interview for DSM-IV, while the specific symptoms were examined in the patients by means of the Impact of Event Scale for PTSD and the traumas experienced were assessed by using the Life Events Checklist. BDNF plasma levels were evaluated by means of a standardized Elisa method. The results, while showing significantly lower BDNF levels in PTSD patients, as compared with those of healthy subjects (p = 0.001), although obtained in a small sample size, would suggest that this NT may be involved in the pathophysiology of PTSD.