Embryonic development of four different subsets of cholinergic neurons in rat cervical spinal cord

The developmental stage at which a neuron becomes committed to a neurotransmitter phenotype is an important time in its ontogenetic history. The present study examines when choline acetyltransferase (ChAT) is first detected within each of four different subsets of cholinergic neurons previously identified in the cervical enlargement of the spinal cord: namely, motor neurons, partition cells, central canal cluster cells, and dorsal horn neurons. By examining the temporal sequence of embryonic development of these cholinergic neurons, we can infer the relationships between ChAT expression and other important developmental events. ChAT was first detected reliably on embryonic day 13 (E13) by both biochemical and immunocytochemical methods, and it was localized predominantly within motor neurons. A second group of primitive-appearing ChAT-positive cells was detected adjacent to the ventricular zone on E14. These neurons seemed to disperse laterally into the intermediate zone by E15, and, on the basis of their location, were tentatively identified as partition cells. A third group of primitive ChAT-immunoreactive cells was detected on E16, both within and around the ventral half of the ventricular zone. By E17, some members of this "U"-shaped group appeared to have dispersed dorsally and laterally, probably giving rise to dorsal horn neurons as well as dorsal central canal cluster cells. Other members of this group remained near the ventral ventricular zone, most likely differentiating into ventral central canal cluster cells. Combined findings from the present study and a previous investigation of neurogenesis (Phelps et al.: J. Comp. Neurol. 273:459-472, '88), suggest that premitotic precursor cells have not yet acquired the cholinergic phenotype because ChAT is not detectable until after the onset of neuronal generation for each of the respective subsets of cholinergic neurons. However, ChAT is expressed in primitive bipolar neurons located within or adjacent to the germinal epithelium. Transitional stages of embryonic development suggest that these primitive ChAT-positive cells migrate to different locations within the intermediate zone to differentiate into the various subsets of mature cholinergic neurons. Therefore, it seems likely that spinal cholinergic neurons are committed to the cholinergic phenotype at pre- or early migratory stages of their development. Our results also hint that the subsets of cholinergic cells may follow different migration routes. For example, presumptive partition cells may use radial glial processes for guidance, whereas dorsal horn neurons may migrate along nerve fibers of the commissural pathway. Cell-cell interactions along such diverse migratory pathways could play a role in determining the different morphological, and presumably functional, phenotypes expressed by spinal cholinergic neurons.     

胶质源性神经营养因子对脊髓损伤后前角运动神经元的保护作用

目的 :探讨胶质细胞源性神经营养因子 (GDNF)对脊髓损伤后运动神经元的保护作用。 方法 :大鼠分为假手术组、生理盐水 (NS)组和 GDNF组 ,改良 Allen法撞击致伤 T1 2 脊髓 ,蛛网膜下腔分别给予 NS和 GDNF,分别取不同时间的伤段脊髓进行切片 ,应用酶组织化学染色方法显示脊髓前角外侧核运动神经元中胆碱酯酶 (Ch E)和酸性磷酸酶 (ACP)活性 ,并结合计算机进行图像分析。结果 :GDNF组较 NS组 Ch E活性显著增加 ,ACP活性显著降低 ;2 1d时 NS组的 ACP及 Ch E活性均高于及低于假手术组 ;GDNF组与假手术组 Ch E和 ACP活性差别不显著。 结论 :GDNF对脊髓损伤后的前角外侧核运动神经元有一定的保护作用     

Neural basis of implicit motor sequence learning: Modulation of cortical power

Implicit sequence learning describes the acquisition of serially ordered movements and sequentially structured cognitive information, that occurs without awareness. Theta, alpha and beta cortical oscillations are present during implicit motor sequence learning, but their role in this process is unclear. The current study addressed this gap in the literature. A total of 50 healthy adults aged between 19 and 37 years participated in the study. Implicit motor sequence learning was examined using the Serial Reaction Time task where participants unknowingly repeat a sequence of finger movements in response to a visual stimulus. Sequence learning was examined by comparing reaction times and oscillatory power between sequence trials and a set of control trials comprising random stimulus presentations. Electroencephalography was recorded as participants completed the task. Analyses of the behavioral data revealed participants learnt the sequence. Analyses of oscillatory activity, using permutation testing, revealed sequence learning was associated with a decrease in theta band (4–7 Hz) power recorded over frontal and central electrode sites. Sequence learning effects were not observed in the alpha (7–12 Hz) or beta bands (12–20 Hz). Even though alpha and beta power modulations have long been associated with executing a motor response, it seems theta power is a correlate of sequence learning in the manual domain. Theta power modulations on the serial reaction time task may reflect disengagement of attentional resources, either promoting or occurring as a consequence of implicit motor sequence learning     

脑缺血再灌注期间海马CA1区微管运动蛋白活性变化

研究脑缺血再灌注期间海马ＣＡ１区锥体细胞微管运动蛋白活性的变化。方法沙土鼠前脑缺血再灌注,脑缺血１０ｍｉｎ。将２０只土鼠随机分为４组：假手术组、再灌注Ⅰ组（再灌注６ｈ）、再灌注Ⅱ组（再灌注４８ｈ）、再灌注Ⅲ组（再灌注９６ｈ）。采用免疫组织化学方法结合计算机图像分析测定脑缺血再灌注期间海马神经元微管运动蛋白活性。结果脑缺血再灌注期海马ＣＡ１区微管运动蛋白活性明显下降,在再灌注６ｈ,４８ｈ,９６ｈ时期     

Medical assessment for licensing of taxi drivers by Scottish Local Authorities

In the UK, licensing of taxi drivers is dealt with by localgovernment authorities. In Scotland, before the recent reorganizationof local government, taxi licensing was under the jurisdictionof District Councils, so a telephone survey was conducted ofall 52 mainland Scottish District Councils to ascertain theprocedures which were being employed in assessing medical fitnessto drive a taxi, for which there is no national standard. Medicalenquiries relevant to fitness to drive were being made by 41(79%) of local authorities, but in 38 (73%) this was limitedto a single question about health. No enquiry regarding healthstatus was being made by 11 (21%) District Councils (all serving< 100,000 population size). Only three Scottish DistrictCouncils conducted a routine medical examination of all applicants.Thirteen of the 15 large (> 100,000 population size), and20 of the 21 medium-sized (50,000–100,000) Scottish DistrictCouncils carried out medical examinations either when a relevantmedical disorder was declared by the applicant, or when theapplicant was above a defined age (which varied between localauthorities). The small local authorities (population < 50,000)examined only those applicants who declared medical disorders.This survey has shown considerable variation and limitationsin the approach of the previously existing Scottish DistrictCouncils to the assessment of medical fitness to drive of applicantsfor taxi licences. It is suggested that national standards andguidelines are required for medical fitness to drive in relationto taxi licensing.     

Autosomal recessive hypermyelinating neuropathy

We studied three patients from two kinships, affected by early onset hereditary motor and sensory neuropathy with probable autosomal recessive inheritance (HMSN type III). Morphological studies of sural nerve biopsies revealed an abnormal myelin proliferation. Two adult patients with long-term follow up, lost ability to walk at 28 and 22 years and showed severe involvement of the cranial nerves. Our observations suggest that hypermyelination neuropathy with early onset is a progressive disease with poor long-term prognosis. In one kinship the occurrence of the disease in two sibs of both sexes but not in parents, is consistent with an autosomal recessive inheritance. Familial cases of hypermyelination neuropathy have not been described in previous reports. Morphological aspects of this condition are compared with other forms of hypermyelination neuropathy.Supported by Telethon-Italy for the project: Chronic inflammatory polyradiculoneuropathy: electrophysiological and immunopathological studies     

A comparative trial of anti-glycoconjugate antibody assays: IgM antibodies to GM1

IgM class antibodies against the ganglioside GM1 have been found in a subgroup of patients with lower motor neuron syndromes and multifocal motor neuropathies (MMN). The pathogenic relevance of these antibodies is still unclear, but some MMN patients with IgM antibodies against GM1 seem to profit from immunosuppressive therapy. A reliable test for IgM antibodies against GMl may be useful for identifying these patients. We have assessed the comparability of the ELISA tests used for the determination of IgM against GM1 by sending coded serum samples to nine laboratories. In three samples high-titre IgM antibodies against GM1 were detected by all laboratories. This result was confirmed by dot blot immunodetection and thin-layer chromatography immuno-overlay. Seven samples were read as negative by nearly all laboratories. Major discrepancies between laboratories were noted in the analysis of one sample with results ranging from negative to high titre. Participating laboratories: N. Baumann and A. Ben Younes-Chennoufi, Neurobiologie cellulaire moleculaire et clinique, INSERM U134, Hôpital de la Sâpetrière, Paris, France; P. Fredman and L. Svennerholm, Department of Psychiatry and Neurochemistry, Goteborg University, Sweden; N. Gregson and R. A. C. Hughes, Department of Neurology, Guy's and St. Thomas's Medical and Dental School, London, UK; A. A. Ilyas, Department of Neurosciences, University of Medicine & Dentistry of New Jersey, New Jersey Medical School, Newark, N. J., USA; A. Pestronk, Division of Neuromuscular Diseases, Washington University School of Medicine, St. Louis, Mo., USA; A. J. Steck, Service de Neurologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (current address: Department of Neurology, University of Basle); H. Willison, Department of Neurology, University of Glasgow, Glasgow, UK     

Synergistic role of muscarinic acetylcholine and tachykinin NK-2 receptors in intestinal peristalsis

It is known that tachykinins (substance P, neurokinin A) participate in the excitatory neural pathways subserving peristaltic motor activity in the intestine. The aim of the present study was to elucidate the types of tachykinin receptor (NK-1 or NK-2) involved in peristalsis by the use of receptor subtype-selective antagonists. Peristaltic motility in isolated segments of the guinea-pig ileum was induced by pumping fluid into the oral end of the intestinal segment. By way of the intraluminal pressure the compliance of the intestinal wall during the preparatory phase and the pressure threshold to trigger the emptying phase of peristalsis were recorded. The tachykinin antagonists were used at concentrations that were at least 30 times in excess of the equilibrium dissociation constants which had previously been evaluated with receptor subtype-selective agonists on the guineapig ileum circular muscle. The NK-1 selective antagonist CP-96,345 (0.3 M) had a slight stimulant influence on peristalsis, whereas the NK-2 selective antagonists MEN-10,376 (10 M), GR-94,800 (0.3 M) and SR-48,968 (0.1 M) led to a small inhibition of motor activity. However, when given after exposure of the ileum to a threshold concentration of atropine (5–20 nM) causing little depression of peristalsis, the tachykinin NK-2 receptor antagonists invariably abolished peristalsis. This synergistic interaction was not seen when SR-48,968 was administered after the ileal segments had been exposed to concentrations of hexamethonium, isoproterenol or calcitonin gene-related peptide that by themselves caused a slight inhibition of peristalsis only. CP-96,345 was without effect on peristalsis when it was applied in the presence of a threshold concentration of atropine. These findings indicate that transmission via tachykinin NK-2, but not NK-1, receptors synergizes with cholinergic transmission via muscarinic receptors in the relay of excitatory enteric pathways subserving intestinal peristalsis. Correspondence to: P. Holzer at the above address     

Excitotoxic lesions of the pedunculopontine tegmental nucleus disinhibit orofacial behaviours stimulated by microinjections of d-amphetamine into rat ventrolateral caudate-putamen

Data are presented which support the hypothesis that the pedunculopontine tegmental nucleus serves as an output station for the striatum and, in particular, has a role in the expression of behaviour stimulated from the ventrolateral caudate-putamen, a rodent homologue of the primate putamen. Rats received either bilateral ibotenate or sham lesions in the pedunculopontine tegmental nucleus and bilateral cannulation of the ventrolateral caudate-putamen. Oral motor activities were observed following microinjection of 5.0, 10.0 and 20.0 g d-amphetamine (and vehicle-only control) into the ventrolateral caudate-putamen. As expected, orofacial behaviours such as biting and licking were observed in sham-lesioned rats following this treatment, but pedunculopontine tegmental nucleus-lesioned rats exhibited an increase in the incidence of these oral motor behaviours at all doses of amphetamine compared with the controls. This increase was the product of changes in the duration and number of times in which they engaged in oral motor behaviours, but not the latency to initiate them. There was no change in the normal oral motor activities associated with grooming. Histological analysis showed that ibotenate lesions destroyed both cholinergic and non-cholinergic neurones in the pedunculopontine tegmental nucleus. These data indicate that loss of the pedunculopontine tegmental nucleus disinhibits oral motor behaviours stimulated from the ventrolateral caudateputamen by d-amphetamine and are discussed in terms of their implications for understanding the relationships between striatal outflow and structures in the pons.     

Endothelial lipopigment as an indicator of α-tocopherol deficiency in two equine neurodegenerative diseases

Two spontaneous neurodegenerative diseases of the horse, equine motor neuron disease (EMND) and equine degenerative myeloencephalopathy (EDM), have been associated with -tocopherol deficiency, and both were characterized by prominent accumulations of endothelial lipopigment in the small vessels of the spinal cord. These endothelial pigment deposits appear to be reversible. In EMND horses pasture-supplemented for 9 months or more after the progression of weakness and wasting had arrested, there was very little endothelial lipopigment. The origin and the potential effects of these endothelial lipopigment accumulations are discussed.