大鼠生后锰接触对黑质多巴胺能神经元发育的毒性影响

目的　研究大鼠出生后锰接触对黑质多巴胺 (DA)神经元发育的毒性影响。方法　采用Morris水迷宫试验检测仔鼠的肌力变化 ;荧光分光度计法检测仔鼠尾状核脑匀浆DA含量的变化 ;酪氨酸氢氧化酶(TH)免疫细胞化学 (ABC法 )与图象分析相结合法检测黑质DA神经元和尾状核DA纤维的免疫反应强度和平均相对密度。结果　 (1)随着染锰浓度的增高 ,仔鼠的肌力呈现明显的衰退 ;(2 )尾状核脑匀浆的DA含量 ,随染锰浓度的升高而降低 ;(3)黑质TH免疫反应阳性神经元和尾状核TH免疫反应阳性纤维的反应强度、以及相应的TH阳性产物的平均相对密度 ,均随着染锰浓度的升高而显著下降。结论　大鼠生后锰接触 ,对黑质多巴胺神经元的发育有明显的毒性损害 ,其损害程度随染锰的剂量升高而增加     

Green Synthesis of Silver Nanoparticles Using Populi gemmae Extract: Preparation,Physicochemical Characterization,Antimicrobial Potential and In Vitro Antiproliferative Assessment

Green route is an economic, facile and eco-friendly method, employed for the synthesis of various types of nanoparticles, having it as a starting point biological entity, especially as a plant extract. The present study aims to obtain silver nanoparticles (AgNPs) starting from an ethanolic extract of Populi gemmae (Pg), by adjusting the reaction parameters. The morphological and structural characterization exhibited that both the reaction temperature and the concentration of metal salt, contributes to the obtaining of Pg-AgNPs with adjustable size and shape. The newly synthesized nanoparticles exhibited a good antibacterial activity on Gram-positive bacteria as well as antifungal activity. The in vitro antiproliferative activity of Pg-AgNPs was assessed on two different cancer cell lines (breast cancer cells—MCF7 and lung carcinoma epithelial cells—A549). Results have shown that the green-synthetized Pg-AgNPs_S2 (obtained at 60 °C, using AgNO₃ of 5 M) induced a substantial decrease in tumor cell viability in a dose-dependent manner with an IC₅₀ ranging from 5.03 to 5.07 µg/mL on A549 cell line and 3.24 to 4.93 µg/mL on MCF7 cell line.     

Organization of visual cortical inputs to the striatum and subsequent outputs to the pallido-nigral complex in the monkey.

To determine the organization of visual inputs and outputs of the striatum, we placed multiple retrograde and anterograde tracers into physiologically identified portions of the striatum known to receive inputs from visual cortex in seven macaques. The injection sites included the tail and genu of the caudate nucleus (14 cases), the head of the caudate (1 case), and the ventral putamen (3 cases). Retrogradely labeled cells were located predominantly in layer 5 of the ipsilateral cortex but were also found in layers 3 and 6. After caudate injections, labeled cells were found both in large, nearly continuous regions of cortex topographically related to the site of the injection, and in several smaller cortical regions that were discontinuous and common to many or all of the injection sites. The continuously labeled regions included nearly all known visual cortical areas, except for the striate cortex. After injections in the rostral tail, the continuously labeled region included the rostral portion of Bonin and Bailey's (Urbana: University of Illinois Press. '47) area TE and adjacent portions of TF, TH, TG, and, occasionally, area 35 (Brodmann, Leipzig: J.A. Barth. '09). After injections into the posterior tail and ventral genu, the labeled region shifted posteriorly in TE and TF, and into TEO and the ventral parts of prestriate areas V4, V3, and (sparsely) V2. As the injection site was advanced into the dorsal genu, the labeled region shifted dorsally toward the parietal lobe, including prestriate areas MT and PO, parietal area PG (Brodmann's area 7), the ventral and lateral intraparietal sulcal areas (VIP and LIP, respectively), and area PE and adjacent area LC (Brodmann's areas 5 and 23, respectively). The discontinuous areas labeled by many different injections included the principal sulcus/frontal eye field region, the anterior cingulate cortex, and the superior temporal polysensory area. Thus, whereas temporal, occipital, and parietal visual cortical areas project into the caudate largely according to proximity, certain multimodal cortical areas seem to have a much wider projection. To determine whether visual cortical areas have additional projections to the caudate beyond the territory of our retrograde injection sites in the tail and genu. 3H-labeled amino acids were injected into areas TE, V4, and MT in three additional monkeys. The topographic location of label in the tail and genu of the caudate in these cases was consistent with the results from injections of retrograde tracers into the caudate.(ABSTRACT TRUNCATED AT 400 WORDS)     

Automated assessment of the substantia nigra on susceptibility map-weighted imaging using deep convolutional neural networks for diagnosis of Idiopathic Parkinson's disease

ObjectivesDespite its use in determining nigrostriatal degeneration, the lack of a consistent interpretation of nigrosome 1 susceptibility map-weighted imaging (SMwI) limits its generalized applicability. To implement and evaluate a diagnostic algorithm based on convolutional neural networks for interpreting nigrosome 1 SMwI for determining nigrostriatal degeneration in idiopathic Parkinson's disease (IPD).MethodsIn this retrospective study, we enrolled 267 IPD patients and 160 control subjects (125 patients with drug-induced parkinsonism and 35 healthy subjects) at our institute, and 24 IPD patients and 27 control subjects at three other institutes on approval of the local institutional review boards. Dopamine transporter imaging served as the reference standard for the presence or absence of abnormalities of nigrosome 1 on SMwI. Diagnostic performance was compared between visual assessment by an experienced neuroradiologist and the developed deep learning-based diagnostic algorithm in both internal and external datasets using a bootstrapping method with 10000 re-samples by the “pROC” package of R (version 1.16.2).ResultsThe area under the receiver operating characteristics curve (AUC) (95% confidence interval [CI]) per participant by the bootstrap method was not significantly different between visual assessment and the deep learning-based algorithm (internal validation, .9622 [0.8912–1.0000] versus 0.9534 [0.8779-0.9956], P = .1511; external validation, 0.9367 [0.8843-0.9802] versus 0.9208 [0.8634-0.9693], P = .6267), indicative of a comparable performance to visual assessment.ConclusionsOur deep learning-based algorithm for assessing abnormalities of nigrosome 1 on SMwI was found to have a comparable performance to that of an experienced neuroradiologist.     

大鼠端脑内核团向黑质的传入纤维联系

目的 研究大鼠端脑内核团向黑质的传入纤维联系。方法 应用荧光金（nuorogold,FG）逆行标记法技术将FG泳入一侧黑质,观察双侧端脑内的FG标记细胞分布。结果在泳入区同侧的额叶、颞叶、顶叶、岛叶、伏謦、终纹床核、杏仁中央核、隔核、尾壳核、苍白球、腹侧苍白球、脚内核见到FG逆行标记细胞。结论 大鼠端脑内存在丰富核团向黑质投射。     

Effects of bacterial melanin on motor recovery and regeneration after unilateral destruction of Substantia Nigra pars compacta in rats

We examined the potential neuroprotective action of bacterial melanin (BM) in rats after unilateral destruction of Substantia Nigra pars compacta (SNc) dopaminergic neurons. 24 rats were initially trained to an instrumental conditioned reflex (ICR) and then subjected to unilateral electrolytic destruction of SNc. Unilateral deficit in balancing hindlimb movements was observed in all rats after the destruction. On the next day after the destruction part of the animals (n = 12) was intramuscularly injected with BM solution at the concentration 6 mg/ml (0.17 g/kg). The other 12 operated rats served as a control group. On the second day after the operation the testing of instrumental conditioned reflex was resumed in both groups.     

Bilateral upregulation of α-synuclein expression in the mouse substantia nigra by intracranial rotenone treatment

The pesticide rotenone has been shown to cause systemic inhibition of mitochondrial complex I activity, with consequent degeneration of dopamine neurons along the nigrostriatal pathway, as observed in Parkinson’s disease (PD). Recently, intracranial infusion of rotenone was found to increase the protein levels of the Lewy body constituents, α-synuclein and small ubiquitin-related modifier-1(SUMO-1), in the lesioned hemisphere of the mouse brain. These findings are supportive of a mouse model of PD, but information about the dopamine-synthesizing enzyme, tyrosine hydroxylase (TH), an essential marker of dopaminergic status, was not reported. Clarification of this issue is important because an intracranial rotenone mouse model of Parkinson's disease has not been established. Towards this end, the present study examined the effects of intracranial rotenone treatment on TH and α-synuclein immunohistochemistry in addition to forelimb motor function. Mice were unilaterally infused with either vehicle or rotenone (2 μg/site) in both the medial forebrain bundle and the substantia nigra. The forelimb asymmetry (cylinder) test indicated a significant decrease in use of the contralateral forelimb in lesioned animals as compared to the sham group. Densitometric analysis revealed a significant depletion of TH immunofluorescence within the ipsilateral striatum and substantia nigra of lesioned animals. Moreover, a significant bilateral increase in α-synuclein immunofluorescence was found in the substantia nigra of lesioned mice, as compared to control animals. These findings indicate that this intracranial rotenone mouse model will be useful for studies of neurodegenerative disorders such as PD.     

Substantia nigra echogenicity correlated with clinical features of Parkinson's disease

BackgroundTranscranial sonography can display structural alterations in the substantia nigra (SN) of patients with Parkinson's disease (PD), and is considered to be a potential useful tool for the diagnosis of PD. The aim of this study was to assess the correlation between SN echogenicity and clinical features in Chinese patients with PD.MethodsA total of 420 subjects including 290 patients with PD and 130 controls were recruited from the neurological clinic or the community. Transcranial sonographic evaluations of the SN were performed in all subjects, and motor and non-motor symptoms were thoroughly assessed by a series of rating scales in PD patients.ResultsTwo hundred and one patients were successfully assessed by transcranial sonography. SN hyperechogenicity was found to be associated with male sex (p = 0.004), higher scores on the Unified Parkinson's Disease Rating Scale (UPDRS) part II (p = 0.001) and autonomic symptoms scores (p = 0.003). Moreover, regression analysis revealed that UPDRS part II scores (odds ratio = 1.141, p < 0.001) and gender (odds ratio = 2.409, p = 0.007) could be the independent predictors for SN hyperechogenicity; in addition, among all items of UPDRS part II, speech, dressing, hygiene, and turning in bed and adjusting bed clothes significantly correlated with SN hyperechogenicity.ConclusionsThis is the first report suggesting the correlation between SN echogenicity and UPDRS part II, and we conclude that increased SN echogenicity might reflect more severe disease disability or poorer medical response.     

Differentiating drug-induced parkinsonism from Parkinson's disease: An update on non-motor symptoms and investigations

Drug-induced parkinsonism is the second most common cause of parkinsonism after Parkinson's disease and their distinction has crucial implications in terms of management and prognosis. However, differentiating between these conditions can be challenging on a clinical ground, especially in the early stages. We therefore performed a review to ascertain whether assessment of non-motor symptoms, or use of ancillary investigations, namely dopamine transporter imaging, transcranial sonography of the substantia nigra, and scintigraphy for myocardial sympathetic innervation, can be recommended to distinguish between these conditions.Among non-motor symptoms, there is evidence that hyposmia can differentiate between patients with “pure” drug-induced parkinsonism and those with degenerative parkinsonism unmasked by an anti-dopaminergic drug. However, several issues, including smoking history and cognitive functions, can influence smell function assessment. Higher diagnostic accuracy has been demonstrated for dopamine transporter imaging. Finally, preliminary evidence exists for sympathetic cardiac scintigraphy to predict dopaminergic pathway abnormalities and to differentiate between drug-induced parkinsonism and Parkinson's disease.Imaging of the dopaminergic pathway seems to be the only, reasonably available, technique to aid the differential diagnosis between drug-induced parkinsonism and Parkinson's disease.