苯丙胺致大鼠黑质多巴胺神经元损伤与LaminB1和GRP94的关系

目的探讨苯丙胺对黑质DA神经元损伤的机制。方法将60只大鼠随机分为3组：空白组10只、生理盐水组10只、苯丙胺处理组40只。苯丙胺处理组又随机分为苯丙胺给药（剂量为2．5mg·kg-1·d-1）后1h、1d、7d和14d组,每组各10只。观察给药后的行为学变化,再用Westernblot方法检测各组黑质LaminB1和GRP94蛋白的表达量。结果苯丙胺在首次给药后就可引起大鼠自主活动量的增加。并且随着给药时间的延长出现了刻板行为：Westernblot方法检测黑质GRP94和LaminB1蛋白的表达在各组间未见差异。结论低剂量短时间苯丙胺对黑质DA能神经元的损害可能与GRP94和LaminB1蛋白的变化没有关系。     

REM sleep deprivation generates cognitive and neurochemical disruptions in the intranigral rotenone model of Parkinson's disease

The recently described intranigral rotenone model of Parkinson's disease (PD) in rodents provides an interesting model for studying mechanisms of toxin‐induced dopaminergic neuronal injury. The relevance of this model remains unexplored with regard to sleep disorders that occur in PD. On this basis, the construction of a PD model depicting several behavioral and neurochemical alterations related to sleep would be helpful in understanding the association between PD and sleep regulation. We performed bilateral intranigral injections of rotenone (12 μg) on day 0 and the open‐field test initially on day 20 after rotenone. Acquisition phase of the object‐recognition test, executed also during day 20, was followed by an exact period of 24 hr of rapid eye movement (REM) sleep deprivation (REMSD; day 21). In the subsequent day (22), the rats were re‐exposed to the open‐field test and to the object‐recognition test (choice phase). After the last session of behavioral tests, the rat brains were immediately dissected, and their striata were collected for neurochemical purposes. We observed that a brief exposure to REMSD was able to impair drastically the object‐recognition test, similarly to a nigrostriatal lesion promoted by intranigral rotenone. However, the combination of REMSD and rotenone surprisingly did not inflict memory impairment, concomitant with a moderate compensatory mechanism mediated by striatal dopamine release. In addition, we demonstrated the existence of changes in serotonin and noradrenaline neurotransmissions within the striatum mostly as a function of REMSD and REMSD plus rotenone, respectively. © 2013 Wiley Periodicals, Inc.     

中国人脑黑质立体定向数字化解剖图谱的研究

目的探讨建立立体定向MRI黑质数字化、可视化图谱的可行性,为立体定向功能神经外科提供解剖学依据。方法健康中国自愿者150人,在标准的立体定向空间内进行全脑扫描,测量黑质体积。选取其中30例利用eFilm软件对黑质中心点坐标进行测量。随机选取1名自愿者,利用其成像数据,对黑质进行三维重建,并对其进行可视化、数字化处理。结果黑质的平均体积左侧为（327．26±24．19）mm3,右侧为（307．28±25．11）mm3,左右侧黑质的体积存在显著性差异（P〈0．05）。黑质中央截面的中心点坐标X、Y、Z分别为（8．45±0．69）mm、（一4．36±0．50）mm和（一9．47±0．80）mm,左右侧黑质的中心点坐标无显著性差异（P〉0．05）,性别之间黑质的中心点坐标亦无显著性差异（P〉0．05）。结论建立立体定向MRI黑质数字化、可视化图谱是可行的。     

Age at onset influences neurodegenerative processes underlying PD with levodopa-induced dyskinesias

PurposeRecently, we demonstrated that PD patients with levodopa-induced dyskinesias are characterized by neuroanatomical and functional changes involving the prefrontal cortex. When compared with non-dyskinetic PD patients, dyskinetic PD patients showed increased volume of the inferior frontal cortex and a dysfunctional imbalance between this region and the supplementary motor area during motor task. In the current study, we investigated the impact of age at onset of the disease on the neuroanatomical characteristics of dyskinetic patients, because it is well known that early-onset PD patients usually develop dyskinesias sooner with respect to late-onset PD.MethodsWhole-brain voxel-wise investigations of gray matter volume and cortical thickness were carried out in dyskinetic (n = 33), non-dyskinetic PD patients (n = 33) and in age-sex-matched healthy controls (n = 40). Neuroimaging analyses were performed separately according to the age at onset (early < 50 y > late).ResultsIndependent of age at onset, dyskinetic PD patients showed altered morphology in the inferior frontal cortex when compared with non-dyskinetic patients. Moreover, additional significant abnormalities emerged in the early- and late-onset PD patients when compared to controls. In fact, early-onset dyskinetic patients showed increased volume in a large cluster of the midbrain encompassing substantia nigra and red nucleus, whereas late-onset dyskinetic patients were characterized by abnormal gray matter increase in the supplementary motor area.DiscussionOur findings demonstrate different patterns of brain abnormalities in patients with LID according to age at onset, highlighting the role of the nigral pathology in early-onset and of the cortical pathology in late-onset patients with PD.     

The role of ERK1, 2, and 5 in dopamine neuron survival during aging

Extracellular signal-regulated kinases (ERKs) 1, 2, and 5 have been shown to play distinct roles in proliferation, differentiation, and neuronal viability. In this study, we examined ERK1, 2, and 5 expression and activation in the substantia nigra (SN), striatum (STR), and ventral tegmental area (VTA) during aging. An age-related decrease in phosphorylated ERK5 was observed in the SN and STR, whereas an increase in total ERK1 was observed in all 3 regions. In primary cultures of the SN and VTA, inhibition of ERK5 but not ERK1 and 2 decreased dopamine neuronal viability significantly. These data suggest that ERK5 is essential for the basal survival of SN and VTA dopaminergic neurons. This is the first study to examine ERK1, 2, and 5 expression and activation in the SN, STR, and VTA during aging, and the relative roles of ERK1, 2, and 5 in basal survival of SN and VTA dopaminergic neurons. These data raise the possibility that a decline in ERK5 signaling may play a role in age-related impairments in dopaminergic function.     

Copper pathology in vulnerable brain regions in Parkinson's disease

Synchrotron-based x-ray fluorescence microscopy, immunofluorescence, and Western blotting were used to investigate changes in copper (Cu) and Cu-associated pathways in the vulnerable substantia nigra (SN) and locus coeruleus (LC) and in nondegenerating brain regions in cases of Parkinson's disease (PD) and appropriate healthy and disease controls. In PD and incidental Lewy body disease, levels of Cu and Cu transporter protein 1, were significantly reduced in surviving neurons in the SN and LC. Specific activity of the cuproprotein superoxide dismutase 1 was unchanged in the SN in PD but was enhanced in the parkinsonian anterior cingulate cortex, a region with α-synuclein pathology, normal Cu, and limited cell loss. These data suggest that regions affected by α-synuclein pathology may display enhanced vulnerability and cell loss if Cu-dependent protective mechanisms are compromised. Additional investigation of copper pathology in PD may identify novel targets for the development of protective therapies for this disorder.     

An autoradiographic study of neurotensin receptors in the human hypothalamus

The aim of the present investigation was to determine a detailed mapping of neurotensin (NT) in the human hypothalamus, the brain region involved in neuroendocrine control. For this, we investigated the presence and the distribution of neurotensin binding sites in the human hypothalamus, using an in vitro quantitative autoradiography technique and the selective radioligand monoiodo-Tyr3-neurotensin (2000 Ci/mM). This study was performed on nine adult human postmortem hypothalami. We first determined the biochemical kinetics of the binding and found that binding affinity constants were of high affinity and do not differ significantly between all cases investigated. Our analysis of the autoradiographic distribution shows that NT binding sites are widely distributed throughout the rostrocaudal extent of the hypothalamus. However, the distribution of NT binding sites is not homogenous and regional variations exist. In general, the highest densities are mainly present in the anterior hypothalamic level, particularly in the preoptic region and the anterior boarding limit (i.e. the diagonal band of Broca). Important NT binding site densities are also present at the mediobasal hypothalamic level, particularly in the paraventricular, parafornical and dorsomedial nuclei. At the posterior level, relatively moderate densities could be observed in the mammillary complex subdivisions, apart from the supramammillary nucleus and the posterior hypothalamic area. In conclusion, the present study demonstrates the occurrence of high concentrations of NT binding sites in various structures in many regions in the human adult hypothalamus, involved in the control of neuroendocrine and/or neurovegetative functions.     

Nuclear organization of cholinergic,catecholaminergic, serotonergic and orexinergic systems in the brain of the Tasmanian devil (Sarcophilus harrisii)

This study investigated the nuclear organization of four immunohistochemically identifiable neural systems (cholinergic, catecholaminergic, serotonergic and orexinergic) within the brains of three male Tasmanian devils (Sarcophilus harrisii), which had a mean brain mass of 11.6 g. We found that the nuclei generally observed for these systems in other mammalian brains were present in the brain of the Tasmanian devil. Despite this, specific differences in the nuclear organization of the cholinergic, catecholaminergic and serotonergic systems appear to carry a phylogenetic signal. In the cholinergic system, only the dorsal hypothalamic cholinergic nucleus could be observed, while an extra dorsal subdivision of the laterodorsal tegmental nucleus and cholinergic neurons within the gelatinous layer of the caudal spinal trigeminal nucleus were observed. Within the catecholaminergic system the A4 nucleus of the locus coeruleus complex was absent, as was the caudal ventrolateral serotonergic group of the serotonergic system. The organization of the orexinergic system was similar to that seen in many mammals previously studied. Overall, while showing strong similarities to the organization of these systems in other mammals, the specific differences observed in the Tasmanian devil reveal either order specific, or class specific, features of these systems. Further studies will reveal the extent of change in the nuclear organization of these systems in marsupials and how these potential changes may affect functionality.