Streptozotocin-Induced Diabetic Rats Showed a Differential Glycine Receptor Expression in the Spinal Cord: A GlyR Role in Diabetic Neuropathy.

In the spinal cord, attenuation of the inhibitory action of glycine is related to an increase in both inflammatory and diabetic neuropathic pain; however, the glycine receptor involvement in diabetic neuropathy has not been reported. We determined the expression of the glycine receptor subunits (α1-α3 and ß) in streptozotocin-induced diabetic Long-Evans rats by qPCR and Western blot. The total mRNA and protein expression (whole spinal cord homogenate) of the α1, α3, and ß subunits did not change during diabetes; however, the α2 subunit mRNA, but not the protein, was overexpressed 45 days after diabetes induction. By contrast, the synaptic expression of the α1 and α2 subunits decreased in all the studied stages of diabetes, but that of the α3 subunit increased on day 45 after diabetes induction. Intradermal capsaicin produced higher paw-licking behavior in the streptozotocin-induced diabetic rats than in the control animals. In addition, the nocifensive response was higher at 45 days than at 20 days. During diabetes, the expression of the glycine receptor was altered in the spinal cord, which strongly suggests its involvement in diabetic neuropathy.

Circular RNAs: the next level of gene regulation.

Gene regulation is a highly complex process involving the presence and participation of many molecules and complexes that regulate gene expression in the genome, which occurs in a precise and coordinated way. Among all these regulatory molecules, the circular RNAs (circRNAs) are the most novel and peculiar family of noncoding RNAs (ncRNAs) as they have a circular structure, are very specific on their expression, highly conserved, and highly resistant to degradation. These molecules have been described in recent years as excellent disease markers and as potential therapeutic targets. In this review, we focused on general characteristics and on the evolution of the circRNAs, as well as on their biological functions, emphasizing on their participation in the formation of brain tumors.

Circulating cervical cancer biomarkers potentially useful in medical attention (Review).

Cervical cancer (CC) is a public health problem worldwide, including Mexico. This type of cancer is the fourth most frequent in women worldwide; in Mexico it is the second most common type in women after breast cancer. The diagnosis of CC is based mainly on Pap smears and colposcopy and the identification of molecular tools that serve as a support for these methods is urgent. Regarding this, differential expressions of specific circulating biomolecules has been detected and, based on this, they have been postulated as potential biomarkers for CC diagnosis, prognosis, and/or to identify the response to treatments. Importantly, the combined analysis of these molecules considerably improves their efficacy as biomarkers and their potential use in the medical attention is promising.

MicroRNAs: Beyond Post-transcriptional Regulation of mRNAs.

MicroRNAs (miRNAs), small non-coding RNAs, participate in the transcriptional and post-transcriptional regulation of eukaryotic genes, and are potential biomarkers for diseases. Mature miRNAs can be located in both the nucleus and cytoplasm, where they perform their regulatory function. The discovery of new miRNAs and the identification of their targets and functions are fundamental to understanding the biological processes regulated by them, as well as the role they play in diseases. This present study researched miRNAs function at nuclear level and as circulating molecules.

Expression changes of BIK in breast cancer tissues of different histological subtypes.

OBJECTIVE: The objective of the study was to determine the expression levels of BIK in breast cancer (BC) tissues of different histological subtype and to delve into the participation of BIK in this type of cancer. MATERIALS AND METHODS: BIK and p-BIK (the phosphorylated form) protein expressions were tested by immunohistochemistry in BC tissue microarrays (Tumoral [n = 90] and adjacent [n = 40] tissues). RESULTS: The data revealed an overexpression of BIK in invasive ductal (Grades I, IIA, and IIB) and in lobular (Grades IIA and IIB) carcinomas compared to their respective adjacent tissues. By contrast, canalicular carcinoma (Grades I and IIB) and phyllodes tumors had very low expression levels of BIK. Only levels of p-BIK were shown to be increased in invasive ductal carcinoma (Grades I, IIA, and IIB). Meanwhile, quantitative polymerase chain reaction analysis showed lower BIK levels in MCF-10A and MCF-7 cells than in MDA-MB-231 and human mammary epithelial cells. In agreement with this, BIK protein was shown to be overexpressed in MDA-MB 231 relative to MCF-7 cells. CONCLUSIONS: Our results showed an association between BIK expression and the BC tumor subtype under study, which could be related to different BIK functions in the BC subtypes.

OBJETIVO: Determinar el grado de expresión de BIK en tejidos de cáncer de mama de diferente subtipo histológico para ahondar en la participación de BIK en este tipo de cancer. MÉTODO: Por medio de inmunohistoquímica se determinó la expresión de BIK y de su forma fosforilada (p-BIK) en microarreglos de tejidos (tumores [n = 90] y tejidos adyacentes [n = 40]) y líneas celulares. RESULTADOS: Los datos mostraron una sobreexpresión de BIK en los carcinomas de tipo ductal invasivo (grados I, IIA y IIB) y lobular (grados IIA y IIB) con respecto a sus tejidos adyacentes respectivos. En contraste, el carcinoma canalicular (grados I y IIB) y los tumores filoides mostraron una baja expresión de BIK en relación con sus tejidos adyacentes respectivos. El análisis de la qPCR mostró una menor expresión de BIK en las células MCF-10A y MCF-7 en comparación con las células MDA-MB-231 y HMEC. En concordancia con esto, la expresión proteica de BIK fue mayor en las células MDA-MB 231 que en las células MCF-7. CONCLUSIÓN: Nuestros resultados mostraron una asociación entre la expresión de BIK y el subtipo tumoral en estudio, lo cual sugiere una función diferencial de BIK en el cáncer de mama.

Long Interspersed Nuclear Elements 1 (LINE1): The chimeric transcript L1-MET and its involvement in cancer.

Long interspersed nuclear elements 1 (LINE1) are non-LTR retrotransposons that represent the greatest remodeling force of the human genome during evolution. Genomically, LINE1 are constituted by a 5´ untranslated region (UTR), where the promoter regions are located, three open reading frames (ORF0, ORF1, and ORF2) and one 3´UTR, which has a poly(A) tail that harbors the short interspersed nuclear elements (SINEs) Alu and SVA. Although the intrinsic nature of LINE1 is to be copied and inserted into the genome, an increase in their mobility produces genomic instability. In response to this, the cell has "designed" many mechanisms controlling the retrotransposition levels of LINE1; however, alterations in these regulation systems can increase LINE1 mobility and the formation of chimeric genes. Evidence indicates that 988 human genes have LINE1 inserted in their sequence, resulting in the transcriptional control of genes by their own promoters, as well as by the LINE1 antisense promoter (ASP). To date, very little is known about the biologic impact of this and the L1-MET chimera is a more or less studied case. ASP hypomethylation has been observed in all studied cancer types, leading to increased L1-MET expression. In specific types of cancer, this L1-MET increase controls both low and high MET protein levels. It remains to be clarified if this protein product is a chimeric protein.

Glycine receptor is differentially expressed in the rat retina at early stages of streptozotocin-induced diabetes.

Diabetes mellitus is a metabolic disease that leads to several complications which include retinopathy. Neuronal abnormalities have been reported to appear before microvasculature alterations. We analyzed the expression levels of GlyR subunits in the retina at 7, 20, and 45 days after streptozotocin-induced diabetes to gain insight into the pathogenesis of diabetic retinopathy. We determined the mRNA and protein expression by qPCR and western blot, respectively. The mRNA and protein expression of the α1 subunit was not altered over the study period; however, they were slightly reduced in α2 yet statistically significant. While protein expression of α3 subunit was only reduced at 45 days diabetes. The mRNA and protein expression of the α4 subunit was remarkably decreased since day 7 of diabetes, remaining only ∼20% on day 45 of diabetes. Surprisingly, the mRNA of the ß subunit was highly increased, while its protein levels were not changed. The decrease in GlyR α subunits expression in the retina from diabetic animals suggest a perturbation in the inhibitory glycine signaling pathway, which might be related to the visual alterations observed in diabetes.

Circulating microRNAs as Biomarkers for Pediatric Astrocytomas.

BACKGROUND AND AIMS: Since MicroRNAs (miRNAs) are potent regulators of gene expression, their expression and function alterations are associated with different types of cancer, including pediatric astrocytoma. Since the secretion of miRNAs by tumors into corporal fluids has made it possible to identify biomarkers in cancer, their deter mination in pediatric astrocytoma is vital. In order to gain insight into the mechanisms controlled by miRNAs in these neoplasms, we tested the expression of miRNAs 130a, 145, 335, 1303, and let-7g-3p by qPCR in tumors and blood serum from pediatric patients with astrocytoma. The data was analyzed with the DIANA-miRPath v3.0 platform. RESULTS: The data represented expression changes of all mirRNAs tested in both tumors and blood serum, which strongly suggest their use as circulating biomarkers for astrocytic tumors. The bioinformatic analysis -with DIANA-miRPath v3.0- showed the involvement of these miRNAs in extracellular matrix (ECM)-receptor interaction and proteoglycans in cancer, which control many hallmarks of cancer. In fact, the expression of the proteoglycan syndecan 4 (SDC4) and that of its biosynthetic enzymes, Exostosin Glycosyltransferase 1 (EXT1) and Xylosyltransferase 1 (XYLT1), were altered in pediatric astrocytoma. CONCLUSIONS: Our results highlight the role of microRNAs in the biology of pediatric astrocytoma and demonstrated for the first time the potential use of some circulating microRNAs as non-invasive biomarkers for this type of tumors, particularly miRs 130a, 145, and 335.

Glycine receptor subunits expression in the developing rat retina.

BACKGROUND AND METHODS: Glycine receptor (GlyR) consists of two α (1-4) and three ß subunits. Considerable evidence indicates that the adult retina expresses the four types of α subunits; however, the proportion of these subunits in adult and immature retina is almost unknown. In this report we have studied mRNA and the protein expression of GlyR subunits in the retina during postnatal rat development by Real-Time qRT-PCR and western blot. RESULTS: mRNA and protein expression indicated a gradual increase of the α1, α3, α4 and ß GlyR subunits during postnatal ages tested. The mRNA ß subunit showed higher expression levels (∼3 fold) than those observed for the α1 and α3 subunits. Very interestingly, the α2 GlyR subunit had the highest expression in the retina, even in the adult. CONCLUSIONS: These results revealed the expression of GlyR at early postnatal ages, supporting its role in retina development. In addition, our results indicated that the adult retina expressed a high proportion of the α2 subunit, suggesting the expression of monomeric and/or heteromeric receptors. A variety of studies are needed to further characterize the role of the specific subunits in both adult and immature retina.

Differentially Expressed Long Non-Coding RNAs Were Predicted to Be Involved in the Control of Signaling Pathways in Pediatric Astrocytoma.

Expression changes for long non-coding RNAs (lncRNAs) have been identified in adult glioblastoma multiforme (GBM) and in a mixture of adult and pediatric astrocytoma. Since adult and pediatric astrocytomas are molecularly different, the mixture of both could mask specific features in each. We determined the global expression patterns of lncRNAs and messenger RNA (mRNAs) in pediatric astrocytoma of different histological grades. Transcript expression changes were determined with an HTA 2.0 array. lncRNA interactions with microRNAs and mRNAs were predicted by using an algorithm and the LncTar tool, respectively. Interactomes were constructed with the HIPPIE database and visualized with the Cytoscape platform. The array showed expression changes in 156 and 207 lncRNAs in tumors (versus the control) and in pediatric GBM (versus low-grade astrocytoma), respectively. Predictions identified lncRNAs that have putative microRNA binding sites, which might suggest that they function as sponges in these tumors. Also, lncRNAs were shown to interact with many mRNAs, such as Pleckstrin homology-like domain, family A, member 1 (PHLDA1) and sulfatase 2 (SULF2). For example, qPCR found long intergenic non-coding RNA regulator of reprogramming (linc-RoR) expression levels upregulated in pediatric GBM when they were compared with control tissues or with low-grade tumors. Meanwhile, PHLDA1 and ELAV-like RNA binding protein 1 (ELAV1) showed expression changes in tumors relative to the control. Our data showed many lncRNAs with expression changes in pediatric astrocytoma, which might be involved in the regulation of different signaling pathways.

Breast cancer cell line MDA-MB-231 miRNA profile expression after BIK interference: BIK involvement in autophagy.

B-cell lymphoma 2 (BCL2)-interacting killer (apoptosis inducing) (BIK) has been proposed as a tumor suppressor in diverse types of cancers. However, BIK's overexpression in breast cancer (BC) and in non-small lung cancer cells (NSCLCs), associated with a poor prognosis, suggests its participation in tumor progression. In this study, we evaluated the global expression pattern of microRNAs (miRNAs), messenger RNA (mRNA) expression changes in autophagy, and autophagic flux after BIK interference. BIK gene expression was silenced by small interfering RNA (siRNA) in BC cell MDA-MB-231, and BIK interference efficiency was tested by real-time PCR and by Western blotting. BIK expression levels decreased by 75 ± 18 % in the presence of 600 nM siRNA, resulting in the abolishment of BIK expression by 94 ± 30 %. BIK interference resulted in the overexpression of 17 miRNAs that, according to the DIANA-miRPath v3.0 database, are mainly implied in the control of cell signaling, gene expression, and autophagy. The autophagy array revealed downregulation of transcripts which participate in autophagy, and their interactome revealed a complex network, where hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), α-synuclein (SNCA), unc-51-like autophagy activating kinase 1/2 (ULK1/2), and mitogen-activated protein kinase 3 (MAPK3) were shown to be signaling hubs. LC3-II expression-an autophagy marker-was increased by 169 ± 25 % after BIK interference, which indicates the involvement of BIK in autophagy. Altogether, our results indicate-for the first time-that BIK controls the expression of miRNAs, as well as the autophagic flux in MDA-MB-231 cells.

Involvement of multiple cellular pathways in regulating resistance to tamoxifen in BIK-suppressed MCF-7 cells.

Majority of women with estrogen receptor (ER)-positive breast cancers initially respond to hormone therapies such as tamoxifen (TAM; antagonist of estrogen). However, many tumors eventually become resistant to TAM. Therefore, understanding the various cellular components involved in causing resistance to TAM is of paramount importance in designing novel entities for efficacious hormone therapy. Previously, we found that suppression of BIK gene expression induced TAM resistance in MCF-7 breast cancer cells. In order to understand the response of these cells to TAM and its association with resistance, a microarray analysis of gene expression was performed in the BIK-suppressed MCF-7 cells and compared it to the TAM-only-treated cells (controls). Several genes participating in various cellular pathways were identified. Molecules identified in the drug resistance pathway were 14-3-3z or YWHAZ, WEE1, PRKACA, NADK, and HSP90AA 1. Further, genes involved in cell cycle control, apoptosis, and cell proliferation were also found differentially expressed in these cells. Transcriptional and translational analysis of key molecules such as STAT2, AKT 3, and 14-3-3z revealed similar changes at the messenger RNA (mRNA) as well as at the protein level. Importantly, there was no cytotoxic effect of TAM on BIK-suppressed MCF-7 cells. Further, these cells were not arrested at the G0-G1 phase of the cell cycle although 30 % of BIK-suppressed cells were arrested at the G2 phase of the cycle on TAM treatment. Furthermore, we found a relevant interaction between 14-3-3z and WEE1, suggesting that the cytotoxic effect of TAM was prevented in BIK-suppressed cells because this interaction leads to transitory arrest in the G2 phase leading to the repair of damaged DNA and allowing the cells to proliferate.

[Genomics in medicine]. / La genómica en la medicina.

The development of new fields of study in genetics, as the -omic sciences (transcriptomics, proteomics, metabolomics), has allowed the study of the regulation and expression of genomes. Therefore, nowadays it is possible to study global alterations--in the whole genome--and their effect at the protein and metabolic levels. Importantly, this new way of studying genetics has opened new areas of knowledge, and new cellular mechanisms that regulate the functioning of biological systems have been elucidated. In the clinical field, in the last years new molecular tools have been implemented. These tools are favorable to a better classification, diagnosis and prognosis of several human diseases. Additionally, in some cases best treatments, which improve the quality of life of patients, have been established. Due to the previous assertion, it is important to review and divulge changes in the study of genetics as a result of the development of the -omic sciences, which is the aim of this review.

El desarrollo de nuevas áreas de estudio dentro de la genética, como las ciencias ómicas (transcriptómica, proteómica, metabolómica), ha permitido estudiar al genoma a diferentes niveles de regulación y expresión. Gracias a esto, actualmente se pueden estudiar las alteraciones génicas de un organismo de forma global ("genoma") y se puede identificar el efecto que tienen estas alteraciones a nivel de proteína y de la producción de metabolitos. De manera importante, esta nueva forma de estudiar la genética ha abierto nuevos campos de conocimiento y ha dilucidado nuevos mecanismos celulares que rigen el funcionamiento de los sistemas biológicos. A nivel clínico, en los últimos años se han implementado nuevas herramientas moleculares que permiten hacer una mejor clasificación, un mejor diagnóstico, así como un pronóstico más acertado de diversas enfermedades. Asimismo, en algunos casos se han establecido mejores tratamientos que favorecen la calidad de vida de los pacientes. Debido a todo lo anterior, es importante revisar y divulgar el cambio que ha tenido el estudio de la genética gracias al desarrollo de las ciencias ómicas, el cual es el objetivo de esta revisión.

[Genetic variants in miRNAs and its association with breast cancer]. / Variantes genéticas en miRNAs y su asociación con el cáncer de mama.

BACKGROUND: In Mexico, breast cancer represents the first cause of cancer death in females. At the molecular level, non-coding RNAs and especially microRNAs have played an important role in the origin and development of this neoplasm In the Anglo-Saxon population, diverse genetic variants in microRNA genes and in their targets are associated with the development of this disease. In the Mexican population it is not known if these or other variants exist. Identification of these or new variants in our population is fundamental in order to have a better understanding of cancer development and to help establish a better diagnostic strategy. METHODS: DNA was isolated from mammary tumors, adjacent tissue and peripheral blood of Mexican females with or without cancer. From DNA, five microRNA genes and three of their targets were amplified and sequenced. Genetic variants associated with breast cancer in an Anglo- Saxon population have been previously identified in these sequences. RESULTS: In the samples studied we identified seven single nucleotide polymorphisms (SNPs). Two had not been previously described and were identified only in women with cancer. CONCLUSION: The new variants may be genetic predisposition factors for the development of breast cancer in our population. Further experiments are needed to determine the involvement of these variants in the development, establishment and progression of breast cancer.

Antecedentes: en México, el cáncer de mama es la primera causa de muerte por cáncer en la mujer. A nivel molecular, los RNAs no codificantes y, en particular, los microRNAs, han tomado un papel importante en el origen y crecimiento de esta neoplasia. En población anglosajona se han reportado diversas variantes genéticas en los genes que codifican los microRNAs y en sus blancos, que se asocian con esta enfermedad. En la población mexicana se desconoce la existencia de estas u otras variantes; por eso su identificación en nuestra población es decisiva para comprender mejor la patogénesis del cáncer y contribuir a establecer una mejor estrategia diagnóstica. Objetivo: buscar y analizar variantes genéticas de tipo SNPs en cinco genes que codifican microRNAs y en tres sitios blancos de estos relacionados con predisposición al cáncer de mama, de mujeres mexicanas con o sin esta neoplasia. Material y métodos: estudio retrospectivo y longitudinal en el que se aisló ADN de tumores mamarios, tejido adyacente al tumor y sangre periférica de mujeres mexicanas con o sin cáncer. A partir del ADN se amplificaron y secuenciaron cinco genes de microRNAs y tres sitios blanco de estos en los que se han reportado variantes genéticas asociadas con el cáncer de mama en población anglosajona. Resultados: en las muestras estudiadas se identificaron siete polimorfismos de un solo nucleótido (SNPs). Dos son variantes no descritas que se encontraron sólo en mujeres con cáncer. Conclusión: las nuevas variantes identificadas pueden ser factores de predisposición genética para cáncer de mama en nuestra población. Para conocer cuál es la participación de estas variantes en el desarrollo, establecimiento y progresión del cáncer de mama se necesita experimentar más.

Mechanisms associated with resistance to tamoxifen in estrogen receptor-positive breast cancer (review).

Anti-estrogens such as tamoxifen are widely used in the clinic to treat estrogen receptor-positive breast tumors. Patients with estrogen receptor-positive breast cancer initially respond to treatment with anti-hormonal agents such as tamoxifen, but remissions are often followed by the acquisition of resistance and, ultimately, disease relapse. The development of a rationale for the effective treatment of tamoxifen-resistant breast cancer requires an understanding of the complex signal transduction mechanisms. In the present study, we explored some mechanisms associated with resistance to tamoxifen, such as pharmacologic mechanisms, loss or modification in estrogen receptor expression, alterations in co-regulatory proteins and the regulation of the different signaling pathways that participate in different cellular processes such as survival, proliferation, stress, cell cycle, inhibition of apoptosis regulated by the Bcl-2 family, autophagy, altered expression of microRNA, and signaling pathways that regulate the epithelial-mesenchymal transition in the tumor microenvironment. Delineation of the molecular mechanisms underlying the development of resistance may aid in the development of treatment strategies to enhance response and compromise resistance.

Clinical and molecular characterization of a patient with 15q21.2q22.2 deletion syndrome.

We report on a 16-year-old girl with a complex phenotype, including intellectual disability, facial dysmorphisms, and obesity. During her infancy, she presented with weak sucking, global developmental delay, and later with excessive eating with central obesity. The girl was clinically diagnosed with probable Prader-Willi syndrome. Chromosomal analysis showed a de novo deletion 46,XX,del(15)(q21q22). However, the use of the Affymetrix CytoScan HD Array defined the exact breakpoints of the deleted 15q21q22 region. The imbalance, about 10.5 Mb in size, is to date the second largest deletion ever described in this chromosomal region. In addition, our patient carries a microdeletion in the 1q44 region and a gain in 9p24. The array result was arr[hg19] 9p24.1(6,619,823-6,749,335)×3, 1q44(248,688,586-248,795,277)×1, 15q21.2 q22.2(50,848,301-61,298,006)×1. Although our patient presents additional chromosomal alterations, we provide a correlation between the clinical findings and the phenotype of the 15q21 deletion syndrome.

A proteomic approach of pediatric astrocytomas: MiRNAs and network insight.

Pediatric astrocytomas, a leading cause of death associated with cancer, are the most common primary central nervous system tumors found in children. Most studies of these tumors focus on adults, not on children. We examined the global protein and microRNA expression pattern by 2D SDS-PAGE, mass spectrometry (MALDI-TOF), and RT(2) miRNA PCR Array System. Proteomic studies revealed 49 proteins with changes on the expression. Interactome showed that vimentin, calreticulin, and 14-3-3 epsilon protein are hub proteins in these neoplasms. MicroRNA analyses demonstrated for the first time novel microRNAs involved in the astrocytoma biology. In conclusion, our results show that novel proteins and microRNAs with expression changes on pediatric astrocytoma could serve as biomarkers of tumor progression. BIOLOGICAL SIGNIFICANCE: Astrocytomas are tumors that progress rapidly and that invade surrounding tissues. Although some drugs have been developed to treat these neoplasms, the mortality of patients is still very high. In this study, we describe for the first time, to our knowledge, some proteins and miRNAs associated with the biology of astrocytic tumors that could be postulated as possible diagnostic or prognostic biomarkers. Altogether, our results indicate that large-scale analyses allow making a fairly accurate prediction of different cellular processes altered in astrocytic tumors.

El receptor postsináptico de glicina media de forma transitoria y sostenida la inhibición glicinérgica en la retina de los vertebrados / The post-synaptic glycine receptor mediates in a transitory and sustained way the glycinergic inhibition in the vertebrate retina

Introducción. La glicina y el ácido g-aminobutírico son los principales neurotransmisores inhibidores en la retina de los vertebrados. La acción inhibidora de la glicina es mediada por el receptor postsináptico de glicina, que es un canal selectivo al cloruro, constituido por tres subunidades β y dos α (α1 - α4 ) que se antagoniza por el alcaloide estricnina. En la retina se conoce que las cuatro isoformas de la subunidad α se expresan en la capa sináptica interna y que en muy raras ocasiones se localizan en la misma terminal sináptica. Los receptores de glicina formados por las isoformas α1 o α3 poseen cinéticas rápidas, mientras que los receptores α2 o α4 responden tónicamente. El empleo de ratones transgénicos que tienen eliminada (knock-out) o disminuida (knock-down) la expresión de alguno de los genes que codifican para las diferentes isoformas de la subunidad α del receptor de glicina ha permitido estudiar la participación de estas subunidades en la transmisión glicinérgica de la retina de los mamíferos. Objetivo. Describir la participación del receptor de glicina en la neurotransmisión glicinérgica, particularmente en la retina. Desarrollo. En esta revisión se describen los experimentos que han permitido localizar e identificar la participación de los diferentes subtipos del receptor de glicina en circuitos de neurotransmisión específicos en la retina de los vertebrados. Conclusiones. La localización de receptores de glicina constituidos por diferentes isoformas de la subunidad α, en tipos neuronales específicos, indica la presencia de circuitos glicinérgicos que codifican de manera distinta el paso de información en la retina (AU)

Introduction. Glycine and the g-aminobutyric acid are the principal inhibitory neurotransmitters in the vertebrate retina. The inhibitory action of glycine is mediated by the post-synaptic glycine receptor, a chloride-selective channel, constituted by three β and two α subunits (α1 - α4 ), which is antagonized by the alkaloid strychnine. In the retina, it is known that all α isoforms are expressed at the level of the inner synaptic layer with a very low colocalization. The glycine receptor formed by either α1 or α3 shows rapid kinetics, whereas α2 or α4 receptors respond tonically. The use of transgenic mice has allowed the study of the different glycine receptor α subunits in the glycinegic neurotransmission of the mammalian retina. Aim. To describe the participation of the glycine receptor in the inhibitory neurotransmission particularly in the retina. Development. In this review we describe the experiments that have allowed the localization and the involvement of the α subunit isoforms in specific transmission circuits of the vertebrate retina. Conclusions. The localization of the glycine receptor conformed by different isoforms of the α subunit in specific neuronal types, indicate the presence of glycinergic circuits that encode information differently in the retina (AU)

[The post-synaptic glycine receptor mediates in a transitory and sustained way the glycinergic inhibition in the vertebrate retina]. / El receptor postsinaptico de glicina media de forma transitoria y sostenida la inhibicion glicinergica en la retina de los vertebrados.

INTRODUCTION: Glycine and the gamma-aminobutyric acid are the principal inhibitory neurotransmitters in the vertebrate retina. The inhibitory action of glycine is mediated by the post-synaptic glycine receptor, a chloride-selective channel, constituted by three beta and two alpha subunits (alpha(1)-alpha(4)), which is antagonized by the alkaloid strychnine. In the retina, it is known that all alpha isoforms are expressed at the level of the inner synaptic layer with a very low colocalization. The glycine receptor formed by either alpha1 or alpha(3) shows rapid kinetics, whereas alpha(2) or alpha(4) receptors respond tonically. The use of transgenic mice has allowed the study of the different glycine receptor alpha subunits in the glycinegic neurotransmission of the mammalian retina. AIM: To describe the participation of the glycine receptor in the inhibitory neurotransmission particularly in the retina. DEVELOPMENT: In this review we describe the experiments that have allowed the localization and the involvement of the alpha subunit isoforms in specific transmission circuits of the vertebrate retina. CONCLUSIONS: The localization of the glycine receptor conformed by different isoforms of the alpha subunit in specific neuronal types, indicate the presence of glycinergic circuits that encode information differently in the retina.