蜥蜴中脑神经通路和起源细胞的形态

本文采用 HRP 法研究了蛤蚧(Gekko gekko)和鳄蜥(Shinisaurus crocodilurus)视顶盖、中脑深核(NPM)与峡核之间的通路和起源细胞的形态。结果指出:1.顶盖与峡核大细胞部(Imc)呈相互区域对应投射;2.同侧顶盖—Imc 投射细胞主要位于第7层,系有径向树突的梨形细胞;同侧 Imc—顶盖投射细胞为小树突域的梨形或多角形细胞;3.顶盖注射标记的 NPM细胞呈纺锤形,染色浅;峡核注射标记的 NPM 细胞,其粗树突往往伸向顶盖;4.NPM 注射标记顶盖细胞和峡核细胞,前者主要位于顶盖第7层,后者散布在峡核大细胞部(Imc)和峡核小细胞部(Ipc)内。     

Receptive field scatter,topography and map variability in different layers of the hindpaw representation of rat somatosensory cortex

We recorded neurons extracellularly in layers II/III, IV, and V of the hindpaw representation of primary somatosensory cortex in anesthetized rats and studied laminar features of receptive fields (RFs) and representational maps. On average, RFs were smallest in layer IV and largest in layer V; however, for individual penetrations we found substantial deviations from this rule. Within the hindpaw representation, a distinct rostrocaudal gradient of RF size was present in all layers. While layer V RFs were generally largest independent of this gradient, layer IV RFs recorded caudally representing the proximal portions of the paw were larger than layer II/III RFs recorded rostrally representing the digits. The individual scatter of the locations of RFs across laminar groups was in the range of several millimeters, corresponding to about 25% of the average RF diameter. The cutaneous representations of the hindpaw in extragranular layers were confined to the areal extent defined by responsive sites in layer IV. Comparison between RFs determined quantitatively and by handplotting showed a reliable correspondence. Repeated measurements of RFs revealed spontaneous fluctuations of RF size of no more than 5% of the initial condition over an observation period of several hours. The topography and variability of cortical maps of the hindpaw representation were studied with a quantitative interpolation method taking into account the geometric centers of RFs and the corresponding cortical recording sites. On average, the overall topography in terms of preservation of neighborhood relations was present in all layers, although some individual maps showed severe distortions of topography. Factors contributing to map variability were overall position of the representation on the cortical surface, internal topography and spatial extent. Interindividual variability of map layout was always highest in the digit representations. Local topographic orderliness was lowest in layer V, but comparable in layers II/III and IV. Within layer IV, the lowest orderliness was observed in the digit representations. Our data emphasize a substantial variability of RF size, overlap and position across layers and within layers. At the level of representational maps, we found a similar degree of variability that often co-varied across layers, with little evidence for significant layer specificity. Laminar differences are likely to arise from the specific input-output pattern, layer-specific cell types and the connectivity between different layers. Our findings emphasizing similarities in the variability across layers support the notion of tightly coupled columnar interactions between different layers.     

Recent advances in understanding the pathogenesis of polyglutamine diseases: involvement of molecular chaperones and ubiquitin-proteasome pathway

Polyglutamine diseases consist of a group of familial neurodegenerative disorders caused by expression of proteins containing expanded polyglutamine stretch. Over the past several years, tremendous progress has been made in identifying the molecular mechanisms by which the expanded polyglutamine tract leads to neuronal dysfunction and neurodegeneration. A common feature of most polyglutamine disorders is the occurrence of ubiquitin-positive neuronal intranuclear inclusions. The appearance of ubiquitinated aggregates implies an underline incapability of the cellular chaperones and proteasome machinery that normally functions to prevent the accumulation of misfolded proteins. Here we review the recent studies that have revealed a critical role for molecular chaperones and ubiquitin-proteasome pathway in the pathogenesis of polyglutamine diseases.     

Dimensional changes of proximal tubules and cortical capillaries in chronic obstructive renal disease

Summary The study was carried out to determine the proximal tubular length, surface area and length of peritubular capillaries and the nephron numbers in kidneys with chronic nephropathy and varying increase in the cortical interstitial volume. Kidneys of pigs with varying chronic obstructive nephropathy were used for the experiments. Two subgroups of ureterobstructed kidneys were defined arbitrarily according to the volume of cortical interstitium. One subgroup (I) comprised kidneys with a volume fraction of cortical interstitium less than 30% (mean 17.2%; mean of controls 9.7%). The other subgroup (II) consisted of kidneys with severe chronic nephropathy and with a volume fraction of interstitium more than 30% (mean 44.5%). Proximal tubular length and length and surface area of peritubular capillaries were assessed by conventional morphometric techniques on 1 m thick sections of plastic embedded material. Nephron numbers were determined by a stereological method for counting glomeruli.The results demonstrated that proximal tubular length and capillary dimensions were significantly reduced in subgroup II, whereas no significant changes were observed in subgroup I. The mean number of glomeruli was not significantly different from control values in any of the subgroups.The results are in line with observations from previous quantitative analyses of proximal tubular cross-sections indicating that proximal tubular dimensions become reduced mainly at advanced stages of chronic nephropathy. The results also indicate that shortening of individual tubules rather than loss of entire nephrons is responsible for the observed reduction in total length of proximal tubules. Finally, the present observations suggest that reduced dimensions of the cortical capillary network may have pathogenetic significance for ongoing proximal tubular atrophy in chronic renal desease.     

Adenosine,l-AP4, and baclofen modulation of paired-pulse potentiation in the dentate gyrus: interstimulus interval-dependent pharmacology

Paired-pulse potentiation of the glutamate-mediated excitatory postsynaptic potential (EPSP) recorded in the dentate gyrus molecular layer is thought to be mediated presynaptically. It is known that the activation of adenosine (A₁) and GABA_B receptors results in the reduction of glutamate release in the dentate molecular layer via presynaptic mechanisms. To examine possible modulatory roles of these receptors on paired-pulse potentiation, we examined the effects of adenosine and baclofen (a GABA_B agonist) on paired-pulse potentiation using extracellular recording from the lateral perforant path in rat hippocampal slices maintained in vitro. We compared these effects with those of l--amino-4-phosphonobutyric acid (l-AP4) over a wide range of interstimulus intervals (ISIs). l-AP4 enhanced paired-pulse potentiation over the full range of ISIs tested (40–800 ms), whereas adenosine enhanced paired-pulse potentiation only at ISIs of 40–100 ms. In contrast, baclofen reduced paired-pulse potentiation only at ISIs of 400–800 ms. Furthermore, baclofen increased the amplitude of lateral perforant path field potentials, previously reported to be baclofen-insensitive. These results suggest that paired-pulse potentiation can be modulated through the activation of adenosine and baclofen receptors, indicate that this modulation is dependent on ISI, and show that there are at least two pharmacologically separable components of paired-pulse potentiation in the dentate gyrus.     

天然免疫模式识别途径:胞外识别与胞内识别

天然免疫系统通常籍模式识别受体识别病原体相关分子模式。取决于感染的性质,模式识别受体通过细胞外 或细胞内途径识别病原体,并传导相应的信号,激活宿主防御应答,消灭入侵病原体。     

Prestress Due to Dimensional Changes Caused by Demineralization: A Potential Mechanism for Microcracking in Bone

Microcracking in bone due to internal strains caused by mineralization is a possible mechanism of damage. Similar damage can be seen in other biological composites such as trees experiencing growth-related prestresses. Dimensional changes in cortical bone due to demineralization and experimental glycation were studied to test whether mineralization-related prestrains are consistent with observed microcracking patterns in bone. A microscopy technique that enables wet measurements of length and angle of milled bone specimens was used. Demineralization of bovine and human bones caused significant anisotropic changes in tissue size. Dimensional changes due to demineralization in bovine bone were prevented or reduced when collagen cross linking was increased by glycation. The dimensional changes of bone caused by demineralization are consistent with the hypothesis that mineralization-caused stresses in remodeling tissue can cause microcracks. © 2002 Biomedical Engineering Society. PAC2002: 8719Rr     

Cenani–Lenz syndrome and other related syndactyly disorders due to variants in LRP4, GREM1/FMN1, and APC: Insight into the pathogenesis and the relationship to polyposis through the WNT and BMP antagonistic pathways

Cenani–Lenz (C–L) syndrome is characterized by oligosyndactyly, metacarpal synostosis, phalangeal disorganization, and other variable facial and systemic features. Most cases are caused by homozygous and compound heterozygous missense and splice mutations of the LRP4 gene. Currently, the syndrome carries one OMIM number (212780). However, C–L syndrome‐like phenotypes as well as other syndactyly disorders with or without metacarpal synostosis/phalangeal disorganization are also known to be associated with specific LRP4 mutations, adenomatous polyposis coli (APC) truncating mutations, genomic rearrangements of the GREM1‐FMN1 locus, as well as FMN1 mutations. Surprisingly, patients with C–L syndrome‐like phenotype caused by APC truncating mutations have no polyposis despite the increased levels of β catenin. The LRP4 and APC proteins act on the WNT (wingless‐type integration site family) canonical pathway, whereas the GREM‐1 and FMN1 proteins act on the bone morphogenetic protein (BMP) pathway. In this review, we discuss the different mutations associated with C–L syndrome, classify its clinical features, review familial adenomatous polyposis caused by truncating APC mutations and compare these mutations to the splicing APC mutation associated with syndactyly, and finally, explore the pathophysiology through a review of the cross talks between the WNT canonical and the BMP antagonistic pathways.     

Small CD4+8+TCRlow thymocytes contain precursors of mature T cells

To evaluate directly the developmental potential of cortical CD4⁺8⁺ thymocytes, highly purified populations of small, nondividing CD4⁺8⁺TCR^low and large, dividing CD4⁺8⁺TCR^high thymocytes from H-2^d mice expressing a transgenic T cell receptor restricted by H-2D^b (major histocompatibility complex class I) molecules were transferred into the thymus of normal, nonirradiated H-2^b recipient mice. The results show that both populations generate CD4^?8⁺ thymocytes under these conditions, thus providing conclusive evidence that small cortical thymocytes do not represent a “dead end” but an important intermediate stage in T cell development.     

Pre‐conditioning activates adenosine utilization in a cost‐effective way during myocardial ischaemia

During pre‐conditioning the interstitial concentration of adenosine, in contrast to lactate, presents a die‐away curve‐pattern for every successive episode of ischaemia. This die‐away pattern might not necessarily be attributed to diminished adenosine production. The present study was undertaken to investigate whether pre‐conditioning alters the metabolic turnover of adenosine as observed by the lactate production during ischaemia. Interstitial levels of metabolites in pre‐conditioned (n=21) and non‐preconditioned (n=21) porcine hearts were monitored with microdialysis probes inserted in both ischaemic and non‐ischaemic tissue in an open chest heart model. Three subgroups perturbated with either plain microdialysis buffer (control), buffer containing adenosine (375 μM ), or buffer containing deoxyadenosine (375 μM ) were studied. All animals were subjected to 90 min of equilibrium microdialysis before 40 min of regional myocardial ischaemia and 120 min of reperfusion. Pre‐conditioning consisted of four repetitive episodes of 10 min of ischaemia and 20 min of reperfusion. Significantly higher levels of inosine and lactate were found in the ischaemic tissue of the pre‐conditioned subgroup receiving adenosine (P < 0.05) compared with the other two subgroups receiving deoxyadenosine and plain buffer, respectively. This difference was only valid for pre‐conditioned ischaemic myocardium, and hence equal amounts of inosine and lactate were produced in the non‐preconditioned ischaemic myocardium regardless of the presence of adenosine or deoxyadenosine. In the non‐ischaemic myocardium baseline levels of metabolites were measured in all subgroups. Pre‐conditioning favoured degradation of exogenous adenosine to inosine successively ending up in enhanced lactate production. This was probably because of the involvement of the hexose monophosphate pathway in the pre‐conditioned ischaemic myocardium. This route may therefore be supplementary in energy metabolism as a metabolic flow can be started by adenosine ending up in lactate without initial adenosine 5′‐triphosphate (ATP) investment. Utilization of adenosine in this way may also explain the successive die‐away pattern of adenosine seen in consecutive pre‐conditioning cycles.