Effects of methamphetamine on locomotor activity and thalamic gene expression in leptin-deficient obese mice

Leptin is an adipose-derived hormone that regulates energy balance. Leptin receptors are expressed in extrahypothalamic sites and several reports showed that leptin can influence feeding and locomotor behavior via direct actions on dopaminergic neurons. The leptin deficient mouse (ob/ob) has been used as an animal model of blunted leptin action, and presents with obesity and mild type 2 diabetes. We used ob/ob mice to study the effect of repeated 7-day methamphetamine (METH) administration analyzing locomotion, behavioral sensitization, and somatosensory thalamic mRNA expression of voltage-gated calcium channels and glutamatergic receptors using RT-PCR. We observed reduced METH-mediated responses in ob/ob mice associated with enhanced in mRNA expression of key voltage-gated and glutamate receptors in the somatosensory thalamus. Results described here are important for understanding the control of locomotion and thalamocortical excitability by leptin.Fil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Gonzalez, Candela Rocio. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Bisagno, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Urbano Suarez, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentin

PLOTTING SLAVES, TALKING ANIMALS: THE POLITICS OF MORALS IN NINETEENTH CENTURY LATIN AMERICAN LITERATURE

This work is a study of the relationship between literature and social criticism in nineteenth century Latin America. More specifically, it is an analysis of the critique of power as it was conveyed by authors from Mexico, Brazil and Argentina through literary genres such as the drama, the short story, the chronicle, and the political satire. It argues that through an aesthetic correlation between certain literary forms (mainly, the tragedy and the animal fable) and morality, these authors exercised a critique of the hegemonic discourse on social and racial domination in their societies. Using the figures of the slave and of the animal, these literary texts were not only criticizing governments and social practices, but also deconstructing the old aristocratic ethics in which the Enlightenment had founded the very legitimation of the modern state. Taking the figures of the slave and the animal as structural and analytical axes, this dissertation is devoted to the reading of six works. In the first section ("Slaves") it deals with three dramas that, invoking the relationship between tragedy and ethics, are proposed as political interventions that deconstruct the figure of the master and its moral contradictions in three post- colonial national scenarios. Despite the fact that its authors belonged to the political elites of their countries, these plays, Mãe (1860), by José de Alencar, Atar-Gull (1855), by Lucio V. Mansilla, and La venganza de la gleba (1906), by Federico Gamboa, are a unique access to the tensions and disarticulations within the national dominant ideologies of the times, and end upshowing how the figure of the slave was already necessary in Eurocentric discourse on legitimate ivpower and, ultimately, on the definition of the human. In the second section ("Fabulous Animals"), this dissertation analyses El gallo pitagórico (1842), by Juan Bautista Morales; Cuentos (1880), by Eduarda Mansilla, and chronicles and stories by Machado de Assis (c.1891- 1906). It argues that the talking animal in these texts (contrary to the norms of European fable) becomes a powerful vehicle for a moral critique that faces the discourse on humanism with its own failures and contradictions

Cocaine alters mouse germ cells epigenome with direct impact on h4ac expression and dna methylation in the sperm

Cocaine intake is associated with testicular toxicity and significantreproductive function impairment. There is accumulating evidencethat cocaine administration can trigger nongenetic inheritancethrough the male germ line affecting development and behavior ofthe offspring. The influence of environmental factors on the epigenomeof male germ cells appears to be most impactful if it happensduring a developmental phase when these cells are epigeneticallyreprogrammed. In the present study, we measured epigenetic marksin isolated germ cells of adult mice treated with cocaine (10 mg/kg) or vehicle, in an intermittent binge protocol (3 i.p. injections, 1h apart, one day on/off for 13 days). We found that chronic cocaineintake disrupts male germ cell epigenetic homeostasis, increasingglobal methylated citocine (5-mC) levels in DNA from germ cells andcauda epididymal sperm (germ cells: vehicle 13.15 ± 0.99 vs cocaine20.113 ± 2.28; sperm: vehicle 15.81 ± 1.08 vs cocaine 21.35± 1.52). Cocaine also increased acetylated histone 4 (H4ac) proteinlevels and decreased class I deacetylases HDAC1/2 mRNA andprotein expression (p<0.05). The mRNA expression levels of classIIa and IIb HDACs were also altered (p<0.05). Immunolocalizationstudies showed that HDAC1/2 were mainly expressed in primaryspermatocytes and H4ac was immunolocalized in late meiotic stagesin vehicle mice while it was detected in primary spermatocytesand in successive stages until round spermatid in cocaine-treatedmice. We observed altered mRNA expression of DNA methylationmarkers in isolated germ cells showing decreased levels of Dnmt3band Tet1 gene expression after cocaine treatment (p<0.05). TET1was mainly immunolocalized in primary spermatocytes in vehicleand cocaine-treated mice. The results presented here broaden thebasic knowledge of the impact of addictive stimulants on testicularpathophysiology, fertility and male reproductive health and implythat altered epigenetic homeostasis by cocaine may have potentialconsequences on future generations.Fil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Gambini Pantoja, Camilo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Vitullo, Alfredo Daniel. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bisagno, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Gonzalez, Candela Rocio. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaLXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica, LXVI Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Asociación Argentina de FisiologíaMar del PlataArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaAsociación Argentina de FisiologíaAsociación Argentina de VirologíaAsociación Argentina de Nanomedicina

Transitando hacia la agroecología

En esta nota se da a conocer un trabajo realizado por el INTA junto a los productores de la Chacra “Buena Vida”, donde se evaluó su avance en la transición al modelo agroecológico de acuerdo con una metodología científica y se lograron proyecciones significativas para el futuro del establecimiento. ¿Qué es agroecológico y qué no lo es? ¿Podemos pasar abruptamente de un sistema a otro sin consecuencias productivas, económicas y de estabilidad del agroecosistema? ¿Cómo se deberían recorrer los caminos de la transición de un modelo a otro? Estas y muchas más preguntas se presentan al abordar la necesidad de contar con nuevos modelos de producción que se integren o reemplacen a los convencionales, basados principalmente en el uso y la dependencia de insumos externos. Con el objetivo de evaluar desde una perspectiva holística el avance de un sistema o un territorio hacia la transición agroecológica, durante las temporadas 2018-2019 un equipo de profesionales del INTA estudió, mediante una metodología común, distintas unidades productivas con las que viene trabajando en el Norte de la Patagonia. En la región del Alto Valle el análisis fue aplicado al establecimiento “Buena Vida” de Vista Alegre (Neuquén). El mismo pertenece a la familia conformada por Martín Acuña y Monica Zapata, la cual estuvo vinculada con la agricultura a través de antecedentes familiares y desde su propia actividad profesional de asesoramiento técnico y docencia y que hace seis años decidió dar un paso más, con la mirada puesta en realizar un emprendimiento productivo, no solo sustentable desde el punto de vista comercial sino centrado en el resguardo del hábitat familiar y su alimentación.EEA Alto ValleFil: Gonzalez, Marcelo Raúl. Instituto Nacional Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Alto Valle. Agencia de Extensión Rural Centenario; ArgentinaFil: Domini, Santiago. Instituto Nacional Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Alto Valle. Agencia de Extensión Rural Cipolletti; ArgentinaFil: Mauricio, Betina. Instituto Nacional Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Alto Valle. Agencia de Extensión Rural Cipolletti; Argentin

Methamphetamine Induces TET1- and TET3-Dependent DNA Hydroxymethylation of Crh and Avp Genes in the Rat Nucleus Accumbens

Methamphetamine (METH) addiction is a biopsychosocial disorder that is accompanied by multiple relapses even after prolonged abstinence, suggesting the possibilities of long-lasting maladaptive epigenetic changes in the brain. Here, we show that METH administration produced time-dependent increases in the expression of corticotropin-releasing hormone (Crh/Crf), arginine vasopressin (Avp), and cocaine- and amphetamine-regulated transcript prepropeptide (Cartpt) mRNAs in the rat nucleus accumbens (NAc). Chromatin immunoprecipitation (ChIP) assays revealed that METH increased the abundance of phosphorylated CREB (pCREB) at the promoter of Cartpt but not at Avp or Crh DNA sequences. In contrast, METH produced DNA hypomethylation at sites near the Crh transcription start site (TSS) and at intragenic Avp sequences. METH also increased DNA hydroxymethylation at the Crh TSS and at intragenic Avp sites. In addition, METH increased the protein expression of ten-eleven-translocation enzymes that catalyze DNA hydroxymethylation. Importantly, METH increased TET1 binding at the Crh promoter and increased TET3 binding at Avp intragenic regions. We further tested the role of TET enzymes in METH-induced changes in gene expression by using the TET inhibitor, 1,5-isoquinolinediol (IQD), and found that IQD blocked METH-induced increases in Crh and Avp mRNA expression. Together, these results indicate that METH produced changes in neuropeptide transcription by both activation of the cAMP/CREB pathway and stimulation of TET-dependent DNA hydroxymethylation. These results provide molecular evidence for epigenetic controls of METH-induced changes in the expression of neuropeptides.Fil: Jayanthi, Subramaniam. National Institutes of Health; Estados UnidosFil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: McCoy, Michael T.. National Institutes of Health; Estados UnidosFil: Ladenheim, Bruce. National Institutes of Health; Estados UnidosFil: Bisagno, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Cadet, Jean Lud. National Institutes of Health; Estados Unido

Modafinil improves methamphetamine-induced object recognition deficits and restores prefrontal cortex ERK signaling in mice

Chronic use of methamphetamine (METH) leads to long-lasting cognitive dysfunction in humans and in animal models. Modafinil is a wake-promoting compound approved for the treatment of sleeping disorders. It is also prescribed off label to treat METH dependence. In the present study, we investigated whether modafinil could improve cognitive deficits induced by sub-chronic METH treatment in mice by measuring visual retention in a Novel Object Recognition (NOR) task. After sub-chronic METH treatment (1 mg/kg, once a day for 7 days), mice performed the NOR task, which consisted of habituation to the object recognition arena (5 min a day, 3 consecutive days), training session (2 equal objects, 10 min, day 4), and a retention session (1 novel object, 5 min, day 5). One hour before the training session, mice were given a single dose of modafinil (30 or 90 mg/kg). METH-treated mice showed impairments in visual memory retention, evidenced by equal preference of familiar and novel objects during the retention session. The lower dose of modafinil (30 mg/kg) had no effect on visual retention scores in METH-treated mice, while the higher dose (90 mg/kg) rescued visual memory retention to control values. We also measured extracellular signal-regulated kinase (ERK) phosphorylation in medial prefrontal cortex (mPFC), hippocampus, and nucleus accumbens (NAc) of METH- and vehicle-treated mice that received modafinil 1 h before exposure to novel objects in the training session, compared to mice placed in the arena without objects. Elevated ERK phosphorylation was found in the mPFC of vehicle-treated mice, but not in METH-treated mice, exposed to objects. The lower dose of modafinil had no effect on ERK phosphorylation in METH-treated mice, while 90 mg/kg modafinil treatment restored the ERK phosphorylation induced by novelty in METH-treated mice to values comparable to controls. We found neither a novelty nor treatment effect on ERK phosphorylation in hippocampus or NAc of vehicle- and METH-treated mice receiving acute 90 mg/kg modafinil treatment. Our results showed a palliative role of modafinil against METH-induced visual cognitive impairments, possibly by normalizing ERK signaling pathways in mPFC. Modafinil may be a valuable pharmacological tool for the treatment of cognitive deficits observed in human METH abusers as well as in other neuropsychiatric conditions.Fil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Raineri Andersen, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Cadet, Jean Lud. National Institute on Drug Abuse. Intramural Research Program; Estados UnidosFil: García Rill, Edgar. University of Arkansas for Medical Sciences; Estados UnidosFil: Urbano Suarez, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Bisagno, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentin

Methamphetamine blunts Ca2+ currents and excitatory synaptic transmission through D1/5 receptor-mediated mechanisms in the mouse medial prefrontal cortex

Psychostimulant addiction is associated with dysfunctions in frontal cortex. Previous data demonstrated that repeated exposure to methamphetamine (METH) can alter prefrontal cortex (PFC)-dependent functions. Here, we show that withdrawal from repetitive non-contingent METH administration (7 days, 1 mg/kg) depressed voltage-dependent calcium currents (ICa) and increased hyperpolarization-activated cation current (IH) amplitude and the paired-pulse ratio of evoked excitatory postsynaptic currents (EPSCs) in deep-layer pyramidal mPFC neurons. Most of these effects were blocked by systemic co-administration of the D1/D5 receptor antagonist SCH23390 (0.5 and 0.05 mg/kg). In vitroMETH (i.e. bath-applied to slices from naïve-treated animals) was able to emulate its systemic effects on ICa and evoked EPSCs paired-pulse ratio. We also provide evidence of altered mRNA expression of (1) voltage-gated calcium channels P/Q-type Cacna1a (Cav2.1), N-type Cacna1b (Cav2.2), T-type Cav3.1 Cacna1g, Cav3.2 Cacna1h, Cav3.3 Cacna1i and the auxiliary subunit Cacna2d1 (α2δ1); (2) hyperpolarization-activated cyclic nucleotide-gated channels Hcn1 and Hcn2; and (3) glutamate receptors subunits AMPA-type Gria1, NMDA-type Grin1 and metabotropic Grm1 in the mouse mPFC after repeated METH treatment. Moreover, we show that some of these changes in mRNA expression were sensitive D1/5 receptor blockade. Altogether, these altered mechanisms affecting synaptic physiology and transcriptional regulation may underlie PFC functional alterations that could lead to PFC impairments observed in METH-addicted individuals.Fil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Rivero Echeto, Maria Celeste Solange. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Muñiz, Javier Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Cadet, Jean Lud. National Institutes of Health; Estados UnidosFil: Garcia Rill, Edgar. University Of Arkansas For Medical Sciences; Estados UnidosFil: Urbano Suarez, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Bisagno, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentin

Endogenously elevated androgens alter the developmental programming of the hypothalamic–pituitary axis in male mice

Transgenic male mice that express human chorionic gonadotropin (hCG) α and β subunits constitutively hypersecrete hCG and produce elevated levels of androgens. The aim of this study was to characterize the hypothalamic–pituitary function of these transgenic (hCGαβ+) males by focusing on FSH regulation. Serum FSH levels and pituitary mRNA expression of Fshb, Lhb, Cga, Gnrhr and Esr1 were reduced, whereas Fst expression was increased in prepubertal hCGαβ+ males as compared with wild-type. In the hypothalamus, Cyp19a1 expression, GnRH concentration and ex-vivo GnRH pulsatility were elevated in prepubertal hCGαβ+ mice, whereas Kiss1 expression was decreased prepubertally and Gad67 expression was elevated neonatally. The effect of androgens on the developmental programming of the hypothalamic–pituitary axis of hCGαβ+ males was evaluated by perinatal and prepubertal antiandrogen (flutamide) administration. Our studies identified a critical window between gestational day 18 and postnatal day 14, during which chronically elevated androgens and/or their locally produced metabolites activate the hypothalamus and concomitantly shut-down the gonadotropin axis.Fil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Ratner, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Di Giorgio, Noelia Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Poutanen, Matti. University of Turku; FinlandiaFil: Huhtaniemi, Lipo T.. Imperial College London; Reino Unido. University of Turku; FinlandiaFil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Efeitos gonadais e extra-gonadais da hipersecreção do hormônio gonadotrofina coriônica humana: avaliação num modelo de camundongos transgênicos

Nuestro grupo de investigación está enfocado en estudiar los efectos gonadales y extra-gonadales que ejerce la hormona gonadotrofina coriónica humana (hCG) sobre la función endocrina y reproductiva, particularmente en condiciones de secreción desregulada y persistente. La tecnología transgénica ha resultado ser una herramienta fundamental a la hora de proveer nuevas evidencias sobre el rol de las gonadotrofinas en la patofisiología reproductiva. En este sentido, los ratones transgénicos hipersecretores de hCG han resultado un excelente modelo para llevar a cabo dichas investigaciones. Hemos realizado estudios de caracterización del modelo, que nos ha permitido tener un profundo conocimiento del mismo e identificar un gran número de anomalías en distintos niveles de regulación endocrina, que serán el foco de atención en futuras investigaciones. Las mismas tienen un considerable potencial en el campo de la biomedicina, ya que ayudarán a identificar los mecanismos regulatorios afectados por un estímulo disruptivo como puede ser una hipersecreción hormonal, y permitirán la exploración de nuevas estrategias terapéuticas que interfieran en las patologías endocrinas asociadas. Nuestras investigaciones sobre el modelo de hipersecreción crónica de hCG en ratones muestran claramente que niveles elevados y persistentes de esta hormona promueven múltiples anomalías endocrinas que están acompañadas de tumores gonadales y extra-gonadales.This investigation is focused in studying the gonadal and extra-gonadal effects that the human chorionic gonadotropin hormone (hCG) exerts on endocrine and reproductive functions, particularly under deregulated and persistent secretion conditions. Transgenic technology has turned out to be a fundamental tool when providing new evidences on the role of gonadotropins in reproductive physiopathology. In this sense, transgenic mice hCG hypersecretion has been an excellent model to perform these investigations. Characterization studies of the model have been developed to identify a great number of anomalies in different levels of endocrine regulation, which will be the center of attention in subsequent investigations. These have a considerable potential in the field of biomedicine and will help to identify the regulatory mechanisms affected by a disruptive stimulus, such as hormonal hypersecretion, and will enable the exploration of new therapeutic strategies to interfere with endocrine pathologies. Our investigations on the model of chronic hypersecretion of hCG in mice show clearly that high and persistent levels of this hormone promote manifold endocrine anomalies that are accompanied by gonadal and extra-gonadal tumorsNosso grupo de pesquisa está focado em estudar os efeitos gonadais e extra-gonadais que exerce o hormônio gonadotrofina coriônica humana (hCG) sobre a função endócrina e reprodutiva, particularmente em condições de secreção desregulada e persistente. A tecnologia transgênica tem resultado ser uma ferramenta fundamental na hora de fornecer novas evidências sobre o papel das gonadotrofinas na patofisiologia reprodutiva. Nesse sentido, os camundongos transgênicos hipersecretores de hCG têm resultado um excelente modelo para levar a cabo tais pesquisas. Temos realizado estudos de caracterização do modelo, que nos têm permitido ter um profundo conhecimento do mesmo e identificar um grande número de anomalias em diferentes níveis de regulação endócrina, que serão o foco de atenção em futuras pesquisas. As mesmas têm um considerável potencial no campo da biomedicina, visto que ajudarão a identificar os mecanismos regulatórios afetados por um estímulo disruptivo como pode ser uma hipersecreção hormonal, e permitirão a exploração de novas estratégias terapêuticas que interfiram nas patologias endócrinas associadas. Nossas pesquisas sobre o modelo de hipersecreção crônica de hCG em camundongos mostram claramente que níveis elevados e persistentes deste hormônio promovem múltiplas anomalias endócrinas que estão acompanhadas de tumores gonadais e extra-gonadais.Fil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Ratner, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Stevens, Guillermina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Pedunculopontine arousal system physiology—Effects of psychostimulant abuse

This review describes the interactions between the pedunculopontine nucleus (PPN), the ventral tegmental area (VTA), and the thalamocortical system. Experiments using modulators of cholinergic receptors in the PPN clarified its role on psychostimulant-induced locomotion. PPN activation was found to be involved in the animal?s voluntary search for psychostimulants. Every PPN neuron is known to generate gamma band oscillations. Voltage-gated calcium channels are key elements in the generation and maintenance of gamma band activity of PPN neurons. Calcium channels are also key elements mediating psychostimulant-induced alterations in the thalamic targets of PPN output. Thus, the PPN is a key substrate for maintaining arousal and REM sleep, but also in modulating psychostimulant self-administrationFil: Urbano Suarez, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Bisagno, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); ArgentinaFil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); ArgentinaFil: Rivero Echeto, Maria Celeste Solange. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Muñiz, Javier A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); ArgentinaFil: Luster, Brennon. University Of Arkansas For Medical Sciences; Estados UnidosFil: D'onofrio, Stasia. University Of Arkansas For Medical Sciences; Estados UnidosFil: Mahaffey, Susan. University Of Arkansas For Medical Sciences; Estados UnidosFil: Garcia Rill, E. University Of Arkansas For Medical Sciences; Estados Unido