N-methyl-d-aspartate receptor independent changes in expression of polysialic acid-neural cell adhesion molecule despite blockade of homosynaptic long-term potentiation and heterosynaptic long-term depression in the awake freely behaving rat dentate gyrus

Investigations examining the role of polysialic acid (PSA) on the neural cell adhesion molecule (NCAM) in synaptic plasticity have yielded inconsistent data. Here, we addressed this issue by determining whether homosynaptic long-term potentiation (LTP) and heterosynaptic long-term depression (LTD) induce changes in the distribution of PSA-NCAM in the dentate gyrus (DG) of rats in vivo. In addition, we also examined whether the observed modifications were initiated via the activation of N-methyl-d-aspartate (NMDA) receptors. Immunocytochemical analysis showed an increase in PSA-NCAM positive cells both at 2 and 24 h following high-frequency stimulation of either medial or lateral perforant paths, leading to homosynaptic LTP and heterosynaptic LTD, respectively, in the medial molecular layer of the DG. Analysis of sub-cellular distribution of PSA-NCAM by electron microscopy showed decreased PSA dendritic labelling in LTD rats and a sub-cellular relocation towards the spines in LTP rats. Importantly, these modifications were found to be independent of the activation of NMDA receptors. Our findings suggest that strong activation of the granule cells up-regulates PSA-NCAM synthesis which then incorporates into activated synapses, representing NMDA-independent plastic processes that act synergistically on LTP/LTD mechanisms without participating in their expression

Sensory Experience Differentially Modulates the mRNA Expression of the Polysialyltransferases ST8SiaII and ST8SiaIV in Postnatal Mouse Visual Cortex

Polysialic acid (PSA) is a unique carbohydrate composed of a linear homopolymer of α-2,8 linked sialic acid, and is mainly attached to the fifth immunoglobulin-like domain of the neural cell adhesion molecule (NCAM) in vertebrate neural system. In the brain, PSA is exclusively synthesized by the two polysialyltransferases ST8SiaII (also known as STX) and ST8SiaIV (also known as PST). By modulating adhesive property of NCAM, PSA plays a critical role in several neural development processes such as cell migration, neurite outgrowth, axon pathfinding, synaptogenesis and activity-dependent plasticity. The expression of PSA is temporally and spatially regulated during neural development and a tight regulation of PSA expression is essential to its biological function. In mouse visual cortex, PSA is downregulated following eye opening and its decrease allows the maturation of GABAergic synapses and the opening of the critical period for ocular dominance plasticity. Relatively little is known about how PSA levels are regulated by sensory experience and neuronal activity. Here, we demonstrate that while both ST8SiaII and ST8SiaIV mRNA levels decrease around the time of eye opening in mouse visual cortex, only ST8SiaII mRNA level reduction is regulated by sensory experience. Using an organotypic culture system from mouse visual cortex, we further show that ST8SiaII gene expression is regulated by spiking activity and NMDA-mediated excitation. Further, we show that both ST8SiaII and ST8SiaIV mRNA levels are positively regulated by PKC-mediated signaling. Therefore, sensory experience-dependent ST8SiaII gene expression regulates PSA levels in postnatal visual cortex, thus acting as molecular link between visual activity and PSA expression

Water Extract from the Leaves of Withania somnifera Protect RA Differentiated C6 and IMR-32 Cells against Glutamate-Induced Excitotoxicity

Glutamate neurotoxicity has been implicated in stroke, head trauma, multiple sclerosis and neurodegenerative disorders. Search for herbal remedies that may possibly act as therapeutic agents is an active area of research to combat these diseases. The present study was designed to investigate the neuroprotective role of Withania somnifera (Ashwagandha), also known as Indian ginseng, against glutamate induced toxicity in the retinoic acid differentiated rat glioma (C6) and human neuroblastoma (IMR-32) cells. The neuroprotective activity of the Ashwagandha leaves derived water extract (ASH-WEX) was evaluated. Cell viability and the expression of glial and neuronal cell differentiation markers was examined in glutamate challenged differentiated cells with and without the presence of ASH-WEX. We demonstrate that RA-differentiated C6 and IMR-32 cells, when exposed to glutamate, undergo loss of neural network and cell death that was accompanied by increase in the stress protein HSP70. ASH-WEX pre-treatment inhibited glutamate-induced cell death and was able to revert glutamate-induced changes in HSP70 to a large extent. Furthermore, the analysis on the neuronal plasticity marker NCAM (Neural cell adhesion molecule) and its polysialylated form, PSA-NCAM revealed that ASH-WEX has therapeutic potential for prevention of neurodegeneration associated with glutamate-induced excitotoxicty

Escrit a la paret.

Sobre el pla d'estudis 1993/94Sobre el plan de estudios 1993/9

03. Edificis plurifamiliars. Conferències Càtedra Blanca

Conferència a càrrec de l'Arquitecte Jordi Garcés, Professor de Projectes a l'Escola Tècnica Superior d'Arquitectura de Barcelona des de 1975. Presentació d'Alberto Peñín, Professor coordinador de l'assignatura Projectes III[m]

Escrit a la paret.

Sobre el pla d'estudis 1993/94Sobre el plan de estudios 1993/9

Long-term central and effector shiv-specific memory t cell responses elicited after a single immunization with a novel lentivector dna vaccine

Prevention of HIV acquisition and replication requires long lasting and effective immunity. Given the state of HIV vaccine development, innovative vectors and immunization strategies are urgently needed to generate safe and efficacious HIV vaccines. Here, we developed a novel lentivirus-based DNA vector that does not integrate in the host genome and undergoes a single-cycle of replication. Viral proteins are constitutively expressed under the control of Tat-independent LTR promoter from goat lentivirus. We immunized six macaques once only with CAL-SHIV-IN- DNA using combined intramuscular and intradermal injections plus electroporation. Antigen-specific T cell responses were monitored for 47 weeks post-immunization (PI). PBMCs were assessed directly ex vivo or after 6 and 12 days of in vitro culture using antigenic and/or homeostatic proliferation. IFN-gamma ELISPOT was used to measure immediate cytokine secretion from antigen specific effector cells and from memory precursors with high proliferative capacity (PHPC). The memory phenotype and functions (proliferation, cytokine expression, lytic content) of specific T cells were tested using multiparametric FACS-based assays. All immunized macaques developed lasting peripheral CD8(+) and CD4(+) T cell responses mainly against Gag and Nef antigens. During the primary expansion phase, immediate effector cells as well as increasing numbers of proliferating cells with limited effector functions were detected which expressed markers of effector (EM) and central (CM) memory phenotypes. These responses contracted but then reemerged later in absence of antigen boost. Strong PHPC responses comprising vaccine-specific CM and EM T cells that readily expanded and acquired immediate effector functions were detected at 40/47 weeks PI. Altogether, our study demonstrated that a single immunization with a replication-limited DNA vaccine elicited persistent vaccine-specific CM and EM CD8(+) and CD4(+) T cells with immediate and readily inducible effector functions, in the absence of ongoing antigen expression

A model of genital herpes simplex virus Type 1 infection in Rhesus Macaques

Background: Although HSV-2 is the major cause of genital lesions, HSV-1 accounts for half of new cases in developed countries. Methods: Three healthy SHIV-SF162P3-infected Indian rhesus macaques were inoculated with 4×10^8 pfu of HSV-1 twice, with the second inoculation performed after the vaginal mucosa was gently abraded with a cytobrush. Results: HSV-1 DNA was detected in vaginal swabs 5 days after the second but not the first inoculation in all three macaques. An increase in inflammatory cytokines was detected in the vaginal fluids of the animals with no or intermittent shedding. Higher frequency of blood α_4β_7^high CD4+ T cells was measured in the animals with consistent and intermitted shedding, while a decrease in the frequency of CD69+ CD4+ T cells was present in all animals. Conclusions: This macaque model of genital HSV-1 could be useful to study the impact of the growing epidemic of genital HSV-1 on HIV infection