癫痫持续状态大鼠的蓝斑组织化学与图像分析研究

作者用马桑内酯致大鼠癫痫持续状态,取蓝斑用荧光组织化学方法显示去甲肾上腺素(NA),并用显微摄影自动曝光时间和图像分析两种方法测定荧光强度。结果:均显示大脑皮质包埋马桑内酯微粒的大鼠癫痫持续发作6小时后,蓝斑中NA荧光增强。用单胺氧化酶组化和图像分析法观察到该处酶活性增强。观察到在癫痫持续状态时NA起了一定的调控作用。     

Urinary output of endogenous monoamine oxidase inhibitor and isatin during acute migraine attacks

Summary Urinary output of endogenous monoamine oxidase (MAO) inhibitory activity, was significantly raised in serial samples collected across a migraine attack compared with collections during attack-free periods and in healthy controls, which did not differ from each other. There was a highly significant correlation in output between isatin, a major fraction of the MAO inhibitory activity, and output of the MAO inhibitory activity itself. However, although there was a tendency towards increased isatin excretion during migraine attacks, it failed to reach statistical significance.     

广泛性焦虑症与抑郁症患者免疫、内分泌及单胺递质的对照研究

目的探讨广泛性焦虑症(GAD)与抑郁症(MD)患者在免疫、内分泌和单胺递质方面的差异。方法 对30例GAD患者(焦虑症组)、38例MD患者(抑郁症组)在治疗(5-羟色胺再摄取抑制剂治疗6~8周)前后分别检测血清白细胞介素2(IL-2)、白细胞介素6(IL-6)、白细胞介素1β(IL-1β)、白细胞介素8(IL-8)、可溶性白细胞介素6受体(SIL-6R)、肿瘤坏死因子α(TNF-α)、皮质醇(CS)、促肾上腺皮质激素(ACTH)、肾上腺素(EPH)和去甲肾上腺素(NE)水平。选择30名年龄和性别与患者组相匹配的健康人为对照组。结果 (1)焦虑症组治疗前IL-8[(122±76)ng／L]、SIL-6R[(2 065±790)ng／L]水平均高于对照组(99±68)ng／L]、[(294±48)ng／L,IL-6水平为(1.6±0.7)ng／L,低于对照组[(5.3±2.7)ng／L],差异均有显著性意义(P<0.05);抑郁症组治疗前IL-2[(7.7±6.7)ng／L]、IL-8[(119±67)ng／L]、SIL-6R[(1308±371)ng／L]水平均高于对照组,差异均有显著性意义(均P<0.05)。经治疗后,焦虑症组IL-6[(4.3±1.2)ng／L]水平较治疗前升高,IL-8[(39±9)ng／L]水平较治疗前降低(P<0.05);抑郁症组IL-2[(2.4±1.2)ng／L]、IL-8[(47±15)ng／L]水平较治疗前降低(P<0.05);均接近于对照组水平(均P>0.05)。(2)焦虑症组治疗前ACIH[(49±28)ng／L]、EPH[(67±45)ng／     

Neurotransmitters in cerebrospinal fluid reflect pathological activity

The excitatory transmitters glutamate and aspartate become toxic whenever their extracellular levels are increased because of neuronal, glial and endothelial impairment. Taurine, a volume-regulating amino acid, is released upon excitotoxin-induced cell swelling. Our aim was to investigate if glutamate and aspartate in cerebrospinal fluid (CSF) reveal neuropathology in neurological patients, and if taurine unmasks glutamate-mediated toxicity. Glutamate and aspartate are doubled in viral meningitis, acute multiple sclerosis (MS) and myelopathy compared with control subjects and patients with peripheral facial nerve palsy. These levels do not coincide with a disturbed blood–brain barrier, as estimated by the albumin ratio, are independent of their precursors (glutamine, asparagine) and are not associated with cell lysis. Taurine is significantly increased in meninigitis, acute MS, and myelopathy, suggesting glutamate-mediated toxicity. Analysis of transmitters in lumbar CSF can be used to identify patients with cerebral and spinal pathology who might benefit from specific receptor-modulating agents.     

Quantification and pharmacological characterization of dialysate levels of noradrenaline in the striatum of freely-moving rats: release from adrenergic terminals and modulation by α2-autoreceptors

Information concerning striatal levels of noradrenaline (NA) remains inconsistent. Here we have addressed this issue using a sensitive method of HPLC coupled to amperometric detection. The NA reuptake-inhibitor, reboxetine, selectively elevated levels of NA versus dopamine (DA), and NA levels were also selectively elevated by the α₂-adrenoceptor (AR) antagonist, atipamezole. The actions of atipamezole were mimicked by the preferential α_2A-AR antagonist, BRL44408, while JO-1 and prazosin, preferential antagonists at α_2C-ARs, caused less marked elevations in NA levels. In contrast to antagonists, the α₂-AR agonist, S18616, decreased NA levels and likewise suppressed those of DA. Unilateral lesions of the substantia nigra with 6-hydroxydopamine depleted DA levels without affecting those of NA. Further, the D₃/D₂ receptor agonist, quinelorane, decreased levels of DA without modifying those of NA. However, the D₃/D₂ receptor antagonists, haloperidol and raclopride, and the DA reuptake-inhibitor, GBR12935, elevated levels of both DA and NA. Levels of 5-HT (but not of NA or DA) were increased only by the 5-HT reuptake-inhibitor, citalopram. They were decreased by S18616 and prazosin, reflecting the inhibitory and excitatory influence of α₂- and α₁-ARs, respectively, upon serotonergic pathways. In conclusion, NA in the striatum is derived from adrenergic terminals. Its release is subject to tonic, inhibitory control by α₂-ARs, possibly involving both α_2A- and α_2C-AR subtypes, though their respective contribution requires clarification. A role of dopaminergic terminals in the reuptake of NA likely explains the elevation in its levels elicited by DA reuptake-inhibitors and D₃/D₂ receptor antagonists.     

Morphologic analysis of rat retinocollicular neuron terminals containing monoamine oxidase

The retino-collicular neuron terminals containing type A monoamine oxidase (MAO-A) in the stratum griseum superficiale of the rat superior colliculus were analyzed to provide a morphologic basis for the physiologic role of these neurons in the visual pathway. A computer-assisted, three-dimensional re-construction of the terminal complex associated with the MAO-A-positive terminals was performed. MAO-A-positive terminals originated in the retina and terminated in the stratum griseum superficiale. This was confirmed by tract tracing and enucleation experiments. The terminals were densely grouped in clusters of irregularly shaped swellings. Electron microscopy revealed that the MAO-A-positive terminals were located in a glomerulus-like structure. In this terminal complex, a significant proportion of the axonal profiles (42.96%) synapsed with the MAO-A-positive terminals. Most of the profiles (24.16%) resembled presynaptic dendrites, which represent intermediate elements between the retinal terminals and conventional dendrites. Unlike the glomerulus in the dorsal lateral geniculate body, the MAO-A-positive terminal swellings were not located in the central part of the terminal complex. The terminals had an irregular shape and were located in the complex. The terminal complex was partially ensheathed by glial processes. Furthermore, the membrane surfaces exhibiting synaptic specializations were very small compared with the total surface of the terminal swellings. The membrane length of the synaptic specialization was 5.38% of the total perimeter of the MAO-A-positive terminals.     

Selective inhibition of MAO-A,not MAO-B,results in antidepressant-like effects on DRL 72-s behavior

The effects of monoamine oxidase inhibitors (MAOIs) that selectively inhibit the MAO-A or MAO-B forms of MAO were studied in rats performing under a differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule of reinforcement. Clorgyline and CGP11305A, irreversible and reversible MAO-A inhibitors, respectively, increased the reinforcement rate, decreased the response rate, and enhanced temporal discrimination. The irreversible MAO-B inhibitor (–)-deprenyl did not produce similar effects. Pargyline did not increase the reinforcement rate at low doses that selectively inhibit MAO-B, but did increase the reinforcement rate at doses that inhibit MAO-A by more than 90%. The present results are in accord with clinical data demonstrating that MAO-A inhibitors are effective therapeutic agents in treating depression while MAO-B inhibitors are of questionable antidepressant efficacy. The present findings provide further evidence that the DRL 72-s schedule may be useful both as a screen for identifying new antidepressants and for investigating the neurochemical effects of antidepressant drugs that are responsible for their therapeutic effects.