Distribution of neurons of origin of zinc-containing projections in the amygdala of the rat

The present study describes the distribution of neurons of origin of zinc-containing pathways in the amygdaloid complex of the rat, using the selenium method for simultaneous retrograde labeling of all zinc-containing neurons. With this method, vesicular ionic zinc is precipitated intravitally with selenium compounds and transported retrogradely to the parent neurons, where it can be visualized by silver amplification. Neurons labeled retrogradely with silver-amplified precipitate were observed in all amygdaloid nuclei except for the lateral olfactory tract nucleus, the accessory olfactory tract nucleus and the central nucleus. Very few labeled cell bodies were seen in the anterior amygdaloid area and the medial nucleus. The amygdalo-hippocampal area and the amygdalo-piriform transition area both showed a substantial number of labeled somata throughout their rostrocaudal extent. In the anterior cortical nucleus, very few labeled cell bodies were found in the rostral pole, whereas they were abundant in the caudal quarter of the nucleus. In the posterolateral cortical nucleus, the number of labeled cell bodies increased gradually; there were none in the rostral pole, but most of the neurons in the caudal part were labeled. The posteromedial cortical nucleus contained a great number of labeled somata, but with some variation in the rostrocaudal extent of the nucleus. Considerable numbers of labeled neurons were observed throughout the lateral nucleus. In the basolateral nucleus, a small number of labeled cell bodies was present in the rostral half, but a gradual increase was observed in the caudal direction. Finally, in the basomedial nucleus, very few labeled cell bodies were present in the rostral two-thirds, whilst a considerable number was encountered in the caudal one-third. Possible functional implications of neuronal zinc are considered. The distribution of neurons of origin of zinc-containing projections has been compared with previously described intrinsic connections of the rat amygdala, and tracts that may possibly be zinc-containing are outlined and discussed. It is concluded that in all probability a substantial proportion of the intrinsic connectivity of the rat amygdaloid complex is zinc-containing.The authors thank Ms. M. Sørensen, Mrs. A. Lyhr, Mr. A. Meier and Mrs. K. Wiedemann for excellent technical help.     

Organization of the neurons of origin of the descending pathways from the ferret superior colliculus

The superior colliculus (SC), through its descending projections to the brainstem and spinal cord, is involved in initiating sensory-driven orienting behaviors. Ferrets are carnivores that hunt both above and below ground using visual (and auditory) cues in the daylight but non-visual cues in darkness and in subterranean environments. The present investigation sought to determine whether the ferret SC shows organizational features similar to those found in other visually dominant animals (e.g. cats), or whether characteristics of colliculi from non-visually dominant animals (e.g. rodents) prevail. Injection of retrograde tracer into the identified targets of the colliculus (cervical spinal cord, the contralateral pontomedullary reticular formation, or the ipsilateral pontine reticular formation) labeled tectospinal, crossed tectoreticular, and ipsilateral tectoreticular neurons, respectively, within the adult ferret SC. Labeled tectospinal and crossed tectoreticular neurons were far outnumbered by neurons with ipsilateral reticular projections. Like those of their visually dominant relatives, ferret tectospinal neurons were well represented throughout the anterior-posterior extent of the SC and crossed tectoreticular neurons tended to be distributed more broadly across the intermediate gray layer than those of rodents. Thus, even though ferrets perform well as subterranean predators where non-visual cues initiate orienting behaviors, these anatomical characteristics indicate that their colliculi are organized similar to that of their visually dominant, carnivorous relatives.     

Rationale for the treatment of cancer with sodium selenite

Epidemiological studies conducted during several decades of the last century have demonstrated the importance of sufficient nutritional supply of selenium (Se) for human health. More importantly, low blood Se levels were found to be associated with an increased incidence and mortality from various types of cancers. Recently, attention of researchers was drawn to the relationship between free radical generation, known otherwise as oxidative stress, and carcinogenesis. It was therefore thought that antioxidants should be beneficial for prevention and inhibition of different malignancies. However, there appeared to be a paradox, because tumor growth is associated with tissue hypoxia that is accompanied by the formation of reductive rather than oxidative free radicals. Various organic and inorganic Se compounds, generally considered to be antioxidants, produced mixed results when tested in animal models and human subjects. Amongst them, sodium selenite has been shown to be the most effective in an in vitro and in vivo carcinogenesis studies. As recently demonstrated, selenite is not an antioxidant, but possesses oxidizing properties in the presence of specific substrates. Thus selenite is capable of oxidizing polythiols to corresponding disulfides, but does not react with monothiols. Such polythiols associated with cancer membrane-bound proteins appear under the reducing conditions of hypoxic tumor tissue. These thiol groups can, in turn, initiate a disulfide exchange reaction with plasma proteins, predominantly with fibrinogen, to form an insoluble and protease-resistant fibrin-like polymer. As the result, tumor cells become surrounded by a coat which masks specific tumor antigens thus allowing cancer cells to escape immune recognition and elimination by natural killer (NK) cells. Selenite by virtue of oxidizing cell membrane thiols, can prevent the formation of the coat and consequently makes cancer cells vulnerable to the immune surveillance and destruction. In addition, selenite may directly activate NK cells, as well as inhibit angiogenesis without undesirable decrease in the oxidative potential of cellular environment. It is, therefore, postulated that sodium selenite, in view of its relative low toxicity, might become a drug of choice for many types of cancer including leukemia.     

亚硒酸钠对人白血病HL-60细胞作用机制的研究

目的和方法：实验观察亚硒酸钠对人急性髓性白血病细胞系ＨＬ－ ６０ 细胞生长增殖、诱导分化、细胞内自由基产生和清除系统以及胞内环核苷酸累积的影响,探索亚硒酸钠对人白血病ＨＬ－ ６０ 细胞作用机制。结果：８ ×１０６ｍｏｌＬ 或更高浓度的亚硒酸钠均可显著抑制ＨＬ－ ６０ 细胞的生长增殖,作用５ ｄ 可在一定程度上诱导ＨＬ－ ６０ 细胞向成熟粒细胞方向分化。８ ×１０６ ｍｏｌＬ 亚硒酸钠作用一段时间,可增强自由基清除系统酶活性,减低胞内自由基水平,降低细胞内ｃＧＭＰ 累积而对ｃＡＭＰ 累积无明显影响。结论：硒的抗白血病作用可能与亚硒酸钠的这些作用相关     

Voltage-gated sodium channel organization in neurons: Protein interactions and trafficking pathways

In neurons, voltage-gated sodium (Nav) channels underlie the generation and propagation of the action potential. The proper targeting and concentration of Nav channels at the axon initial segment (AIS) and at the nodes of Ranvier are therefore vital for neuronal function. In AIS and nodes, Nav channels are part of specific supra-molecular complexes that include accessory proteins, adhesion proteins and cytoskeletal adaptors. Multiple approaches, from biochemical characterization of protein–protein interactions to functional studies using mutant mice, have addressed the mechanisms of Nav channel targeting to AIS and nodes. This review summarizes our current knowledge of both the intrinsic determinants and the role of partner proteins in Nav targeting. A few fundamental trafficking mechanisms, such as selective endocytosis and diffusion/retention, have been characterized. However, a lot of exciting questions are still open, such as the mechanism of differentiated Nav subtype localization and targeting, and the possible interplay between electrogenesis properties and Nav concentration at the AIS and the nodes.     

亚硒酸钠对子宫内膜癌细胞增殖能力的影响

目的: 研究亚硒酸钠(Na₂SeO₃)对子宫内膜癌细胞增殖能力的影响,并探讨其作用机制。方法: 用Na₂SeO₃作用于子宫内膜癌Ishikawa细胞和HEC-1A细胞,MTT法检测细胞增殖能力,流式细胞法测定Na₂SeO₃作用后细胞周期的变化及凋亡情况,Western blotting检测周期蛋白cyclin A的表达。结果: Na₂SeO₃对子宫内膜癌Ishikawa细胞和HEC-1A细胞的增殖均有抑制作用,抑制率在一定浓度范围内与Na₂SeO₃浓度呈正相关,对Ishikawa细胞作用48 h的IC₅₀为3.26 μmol/L,对HEC-1A细胞作用48 h的IC₅₀为4.77 μmol/L。Na₂SeO₃作用后两种细胞G₀/G₁期减少,S期细胞增多,G₂/M期细胞有所增加。作用48 h后两种细胞凋亡率增加。Na₂SeO₃使子宫内膜癌Ishikawa细胞和HEC-1A细胞的cyclin A表达增加。结论: 亚硒酸钠对子宫内膜癌Ishikawa细胞和HEC-1A细胞增殖有抑制作用,其作用机制与上调cyclin A表达,引起细胞周期阻滞和诱导凋亡有关。     

Laminar origin of ipsilateral tectopontine pathways

The purpose of these experiments was to identify the cells of origin of the ipsilateral tectopontine pathways in the grey squirrel (Sciurus carolinensis). Following injections of tritiated amino acids into individual collicular laminae, labelled fibers could be traced to the dorsolateral pontine nuclei and overlying lateral pontine tegmentum. Fibers originating in stratum griseum superficiale terminated most heavily within the pontine nuclei whereas those arising from stratum griseum profundum terminated most heavily within the tegmentum. After horseradish peroxidase was injected into the dorsolateral pontine nuclei, cells labelled with reaction product were found in all 3 grey laminae of the superior colliculus, but the majority were located in stratum griseum superficiale. In contrast, when horseradish peroxidase was injected into the tectorecipient pontine tegmentum, most of the labelled cells were located in stratum griseum profundum.These results indicate that each of the 3 grey laminae of the superior colliculus projects to both the dorsolateral pontine nuclei and the lateral pontine tegmentum. However, the pathway to the pontine nuclei arises chiefly in stratum griseum superficiale while the tectotegmental pathway arises chiefly in stratum griseum profundum.     

Time of origin of neurons of the rat superior colliculus in relation to other components of the visual and visuomotor pathways

Summary Groups of pregnant rats were injected with two successive daily doses of ³H-thymidine from gestational day 12 and 13 (E12+E13) until the day before parturition (E21+22) in order to label all the multiplying precursors of neurons. At 60 days of age the proportion of neurons generated (or no longer labelled) on specific days was determined in the separate layers of the superior colliculus. Neurogenesis begins with the production of a few large multipolar neurons in layers V and IV on day E12; the bulk (87%) of these cells are generated on day E13. This early-produced band of large neurons, the intermediate magnocellular zone, divides the superior colliculus into two cytogenetically distinct regions. In both the deep and the superficial superior colliculus neuron production is relatively protracted. In the deep superior colliculus neuron production peaks on day E15 in layer VII, on day E15 and E16 in layer VI, and on day E16 (the large neurons excluded) in layer V, indicating an inside-out sequence. In the superficial superior colliculus peak production time of layer III cells is on day E15 and of layer IV cells on day E16; peak production time of both layer I and II is on day E16 but in the latter region neuron production is more prolonged and ends on day El8. One interpretation of these results is that the two pairs of superficial layers are produced in an outside-in sequence. These three cytogenetic subdivisions of the superior colliculus may be correlated with its structural-functional parcellation into an efferent spinotectal, a deep somatomotor and a superficial visual component.A comparison of neurogenesis in different components of the visuomotor and visual pathways of the rat indicates that the motor neurons of the extraocular muscles, the abducens, trochlear and oculomotor nuclei, and neurons of the nucleus of Darkschewitsch are produced first. Next in line are source neurons of efferents to the bulb and the spinal cord: those of the Edinger-Westphal nucleus and the intermediate magnocellular zone of the superior colliculus. These are followed by the relay neurons of the dorsal nucleus of the lateral geniculate body. The neurons of the superficial superior colliculus and of the visual cortex implicated in visual sensori-motor integrations are produced last.Abbreviations A aqueduct - ap stratum album profundum (layer VII) - bi brachium of the inferior colliculus - c caudal - CGd central gray, pars dorsalis - CGl central gray, pars lateralis - CGv central gray, pars ventralis - dm deep magnocellular zone - EW Edinger-Westphal nucleus - gi stratum griseum intermediale (layer IV) - gp stratum griseum profundum (layer VI) - gs stratum griseum superficiale (layer II) - IC inferior colliculus - im intermediate magnocellular zone - LGd lateral geniculate nucleus, pars dorsalis - ll lateral lemniscus - lm stratum lemnisci (layer V) - MG medial geniculate nucleus - ND nucleus of Darkschewitsch - NO nucleus of the optic tract - op stratum opticum (layer III) - ot optic tract - r rostral - SC superior colliculus - vIII third ventricle - ZO stratum zonale (layer I) - III oculomotor nucleus - IV trochlear nucleus - Vm mesencephalic nucleus of the trigeminal - VI abducens nucleus     

Zinc-rich afferents to the rat neocortex: projections to the visual cortex traced with intracerebral selenite injections

Infusion of sodium selenite to the occipital cortex of the rat was used for the specific tracing of zinc-rich pathways. Large numbers of labeled somata were found ipsilaterally in the visual, orbital and frontal cortices, and contralaterally in homotopic and heterotopic visual areas. Labeled neurons were also found ipsilaterally in the retrosplenial, parietal, sensory-motor, temporal and perirhinal cortex. In contrast to the cortico-cortical connections, ascending afferents to the visual cortex were not zinc-rich except for a few labeled neurons in the claustrum. Additional injections showed reciprocal zinc-rich connections between the visual cortex and the orbital and frontal cortices. The latter cortices also received ascending zinc-rich afferents from the claustrum. Selenite injections revealed the layered distribution and the morphology of these labeled neurons in the neocortex. Zinc-rich neurons were found in layers II–III, V and VI. However, none was found in layer IV. Zinc-rich somata appeared as pyramidal and inverted neurons. The contrasting chemical properties of cortical and subcortical visual afferents may account for the functional differences between these systems.     

亚硒酸钠对UVB损伤人角质形成细胞的保护作用

目的:研究亚硒酸钠(Na2Se O3)对中波紫外线(UVB)损伤人角质形成细胞的保护作用。方法:培养永生化人角质形成细胞(Ha Ca T细胞),实验分为4组处理:(1)正常对照组;(2)Na2Se O3组:分别加入1 nmol/L、10 nmol/L、50 nmol/L、100 nmol/L、200 nmol/L和1μmol/L的Na2Se O3预孵育24 h;(3)UVB组:300、600和900 J/m2UVB照射;(4)Na2Se O3+UVB组:Na2Se O3预孵育24 h后进行UVB照射。采用MTT法检测细胞增殖活性,采用流式细胞仪检测300 J/m2UVB照射后细胞的凋亡率。结果:(1)UVB组与正常对照组比较,细胞增殖活性显著降低(P0.05),细胞活性与UVB照射剂量呈负相关;(2)Na2Se O3组与正常对照组比较,细胞增殖活性无明显差异;(3)不同浓度Na2Se O3+UVB组与UVB组比较,细胞增殖活性增加,差异显著(P0.05),其中100 nmol/L组促进细胞增殖作用最强;(4)300 J/m2UVB照射后,不同浓度Na2Se O3+UVB组与UVB组比较,凋亡率下降,差异显著(P0.05),其中100 nmol/L组抑制凋亡作用最强。结论:UVB对角质形成细胞有损伤作用,且与照射剂量呈正相关;Na2Se O3具有光保护性能,可减轻UVB辐射损伤人角质形成细胞。     

Enzymatic changes in rat thymus after intraperitoneal injections of adrenocorticotrophic hormone and corticosterone

Intraperitoneal injection in adult male rats with adrenocorticotrophic hormone (ACTH) (0.6 mU daily for 3 days) brought about a marked decrease in the activities of four thymic enzymes studied: glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, isocitric dehydrogenase, malic dehydrogenase. A prominent rise in the levels of these enzymes occurred when ACTH was replaced by corticosterone (1 mg injected daily for 3 days). In adrenalectomized rats, the results were similar to those observed in intact animals. The significance of an increase in transaminase activities after corticosterone treatment, relating to an increase in citric cycle enzymes is discussed. On the other hand, it was suggested that ACTH exerts an extra adrenal effect on the thymus.