Long Term Hippocampal and Cortical Changes Induced by Maternal Deprivation and Neonatal Leptin Treatment in Male and Female Rats

Maternal deprivation (MD) during neonatal life has diverse long-term behavioral effects and alters the development of the hippocampus and frontal cortex, with several of these effects being sexually dimorphic. MD animals show a marked reduction in their circulating leptin levels, not only during the MD period, but also several days later (PND 13). A neonatal leptin surge occurs in rodents (beginning around PND 5 and peaking between PND 9 and 10) that has an important neurotrophic role. We hypothesized that the deficient neonatal leptin signaling of MD rats could be involved in the altered development of their hippocampus and frontal cortex. Accordingly, a neonatal leptin treatment in MD rats would at least in part counteract their neurobehavioural alterations. MD was carried out in Wistar rats for 24 h on PND 9. Male and female MD and control rats were treated from PND 9 to 13 with rat leptin (3 mg/kg/day sc) or vehicle. In adulthood, the animals were submitted to the open field, novel object memory test and the elevated plus maze test of anxiety. Neuronal and glial population markers, components of the glutamatergic and cannabinoid systems and diverse synaptic plasticity markers were evaluated by PCR and/or western blotting. Main results include: 1) In some of the parameters analyzed, neonatal leptin treatment reversed the effects of MD (eg., mRNA expression of hippocampal IGF1 and protein expression of GFAP and vimentin) partially confirming our hypothesis; 2) The neonatal leptin treatment, per se, exerted a number of behavioral (increased anxiety) and neural effects (eg., expression of the following proteins: NG2, NeuN, PSD95, NCAM, synaptophysin). Most of these effects were sex dependent. An adequate neonatal leptin level (avoiding excess and deficiency) appears to be necessary for its correct neuro-programing effect

Long-term effects of intermittent adolescent alcohol exposure in male and female rats

Alcohol is a serious public health concern that has a differential impact on individuals depending upon age and sex. Patterns of alcohol consumption have recently changed: heavy episodic drinking—known as binge-drinking—has become most popular among the youth. Herein, we aimed to investigate the consequences of intermittent adolescent alcohol consumption in male and female animals. Thus, Wistar rats were given free access to ethanol (20% in drinking water) or tap water for 2-h sessions during 3 days, and for an additional 4-h session on the 4th day; every week during adolescence, from postnatal day (pnd) 28–52. During this period, animals consumed a moderate amount of alcohol despite blood ethanol concentration (BEC) did not achieve binge-drinking levels. No withdrawal signs were observed: no changes were observed regarding anxiety-like responses in the elevated plus-maze or plasma corticosterone levels (pnd 53–54). In the novel object recognition (NOR) test (pnd 63), a significant deficit in recognition memory was observed in both male and female rats. Western Blot analyses resulted in an increase in the expression of synaptophysin in the frontal cortex (FC) of male and female animals, together with a decrease in the expression of the CB2R in the same brain region. In addition, adolescent alcohol induced, exclusively among females, a decrease in several markers of dopaminergic and serotonergic neurotransmission, in which epigenetic mechanisms, i.e., histone acetylation, might be involved. Taken together, further research is still needed to specifically correlate sex-specific brain and behavioral consequences of adolescent alcohol exposure

Diferencias individuales en las capacidades de aprendizaje y memoria, y en la vulnerabilidad al deterioro cognitivo inducido por estrés en la rata relación con los niveles de ansiedad y prevención con un péptido sintético mimético de la molécula de adhesión celular neural

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, Departamento de Fisiología Animal II, leída el 25-04-2008Depto. de Genética, Fisiología y MicrobiologíaFac. de Ciencias BiológicasTRUEProQuestpu

Shedding of neurexin 3β ectodomain by ADAM10 releases a soluble fragment that affects the development of newborn neurons.

Neurexins are transmembrane synaptic cell adhesion molecules involved in the development and maturation of neuronal synapses. In the present study, we report that Nrxn3β is processed by the metalloproteases ADAM10, ADAM17, and by the intramembrane-cleaving protease γ-secretase, producing secreted neurexin3β (sNrxn3β) and a single intracellular domain (Nrxn3β-ICD). We further completed the full characterization of the sites at which Nrxn3β is processed by these proteases. Supporting the physiological relevance of the Nrxn3β processing, we demonstrate in vivo a significant effect of the secreted shedding product sNrxn3β on the morphological development of adult newborn neurons in the mouse hippocampus. We show that sNrxn3β produced by the cells of the dentate gyrus increases the spine density of newborn neurons whereas sNrxn3β produced by the newborn neuron itself affects the number of its mossy fiber terminal extensions. These results support a pivotal role of sNrxn3β in plasticity and network remodeling during neuronal development

Long-Term Effects of Intermittent Adolescent Alcohol Exposure in Male and Female Rats

Alcohol is a serious public health concern that has a differential impact on individuals depending upon age and sex. Patterns of alcohol consumption have recently changed: heavy episodic drinking¿known as binge-drinking¿has become most popular among the youth. Herein, we aimed to investigate the consequences of intermittent adolescent alcohol consumption in male and female animals. Thus, Wistar rats were given free access to ethanol (20% in drinking water) or tap water for 2-h sessions during 3 days, and for an additional 4-h session on the 4th day; every week during adolescence, from postnatal day (pnd) 28¿52. During this period, animals consumed a moderate amount of alcohol despite blood ethanol concentration (BEC) did not achieve binge-drinking levels. No withdrawal signs were observed: no changes were observed regarding anxiety-like responses in the elevated plus-maze or plasma corticosterone levels (pnd 53¿54). In the novel object recognition (NOR) test (pnd 63), a significant deficit in recognition memory was observed in both male and female rats. Western Blot analyses resulted in an increase in the expression of synaptophysin in the frontal cortex (FC) of male and female animals, together with a decrease in the expression of the CB2R in the same brain region. In addition, adolescent alcohol induced, exclusively among females, a decrease in several markers of dopaminergic and serotonergic neurotransmission, in which epigenetic mechanisms, i.e., histone acetylation, might be involved. Taken together, further research is still needed to specifically correlate sex-specific brain and behavioral consequences of adolescent alcohol exposure

Neuritogenic and Neuroprotective Properties of Peptide Agonists of the Fibroblast Growth Factor Receptor

Fibroblast growth factor receptors (FGFRs) interact with their cognate ligands, FGFs, and with a number of cell adhesion molecules (CAMs), such as the neural cell adhesion molecule (NCAM), mediating a wide range of events during the development and maintenance of the nervous system. Determination of protein structure, in silico modeling and biological studies have recently resulted in the identification of FGFR binding peptides derived from various FGFs and NCAM mimicking the effects of these molecules with regard to their neuritogenic and neuroprotective properties. This review focuses on recently developed functional peptide agonists of FGFR with possible therapeutic potential

Facilitation of AMPA Receptor Synaptic Delivery as a Molecular Mechanism for Cognitive Enhancement

A small peptide from a neuronal cell adhesion molecule enhances synaptic plasticity in the hippocampus and results in improved cognitive performance in rats

Informe final del Ejercicio Profesional Supervisado, realizado en la Dirección Municipal de la Mujer, de la municipalidad de San Pedro Carchá, Alta Verapaz

El Ejercicio Profesional Supervisado (EPS) de la Carrera de Trabajo Social del Centro Universitario del Norte (CUNOR), se realizó en la Direccion Municipal de la Mujer (DMM) de la Municipalidad de San Pedro Carchá, departamento de Alta Verapaz, durante el periodo del 15 de febrero a 15 de octubre del año dos mil diecisiete, se aplicó la metodología del Centro Latinoamericano de Trabajo Social (CELATS), la cual consta de cuatro momentos: Definición problema objeto intervención (POI), selección de alternativas de acción, ejecución y evaluación, el proceso orienta a delimitar que aspectos de una necesidad social son susceptibles de modificar con nuestra intervención profesional. A través de la aplicación de la metodología del CELATS, se estableció que la necesidad social de las mujeres es de protección y participación, puesto que el incremento de la violencia física, sexual, psicológica y económica es constante se definió que el problema objeto de intervención es la desorganización y falta de coordinación interinstitucional para el fortalecimiento de las mujeres en el Municipio de Carchá. Se incidió en el problema mediante la realización del proceso de fortalecimiento a 1,497 mujeres integrantes de Comités Femeninos de primer nivel en temas de prevención de violencia, organización comunitaria y gestión de proyectos para el desarrollo de las mujeres en áreas urbanas y rurales del Municipio; se realizaron dos charlas con presidentes de COCODE de 20 Microrregiones enfocados a la dignificación de los derechos y equidad de género y así incentivar la participación e inclusión del sector femenino en la toma de decisiones a nivel comunitario y municipal; asimismo se realizaron 5 talleres prácticos-productivos con presidentas de II nivel de comités femeninos de veinte Microrregiones, durante la ejecución de los talleres se orientó sobre la importancia de replicar todo lo nuevo que aprendieron (teórico, práctico) en las comunidades de donde son lideresas. Durante el proceso de intervención se realizaron vínculos con instituciones públicas y privadas para la obtención de los recursos necesarios, entre ellos: personal técnico, materiales, financiero y transporte. Se realizaron acciones de apoyó a la DMM, basadas en la formulación de instrumentos y documentos administrativos, se participó e incidió en la Comisión Municipal de la Mujer, se fortalecieron las reuniones mensuales con presidentas de II nivel de los comités femeninos y se brindó atención y acompañamiento de casos de violencia contra la mujer en el Municipio. Las actividades desarrollas en el Ejercicio Profesional Supervisado Multidisciplinario, fueron a través de los epesistas de las carreras de: Trabajo Social, Pedagogía, Derecho, Medicina, Psicología, Ingeniería en Agronomía, Ingeniería en Gestión Ambiental Local y Arquitectura, los cuales se enfocaron a potencializar las habilidades y conocimientos de los pobladores de la Microrregión 6 Cojaj del Municipio de San Pedro Carchá, bajo los ejes de educación, salud, medio ambiente y organización comunitaria; en respuesta a los cuatro ejes de trabajo, fueron implementados los proyectos de Ambiente Limpio, Vida Saludable y Seguridad Alimentaria Nutricional con énfasis en la diversificación de cultivos. La ejecución de las diferentes actividades tuvo resultados satisfactorios por medio de la participación de la población objeto de intervención, asimismo el apoyo de instituciones públicas y privadas para el desarrollo de cada una de las actividades incluidas dentro de los dos proyectos antes descritos

Maternal immune activation in rats is associated with a lower number of dopamine receptor 3-expressing granulocytes in the male offspring with no alterations in cocaine reward, resistance to extinction or cue-induced reinstatement

ABSTRACTThere is evidence for increased rates of drug use among schizophrenic patients. However, the causality in this relationship remains unclear. In addition, biomarkers of schizophrenia are vital, given the heterogeneous nature of the disorder that can lead to difficulties in the early diagnosis. In the present work, we use a maternal immune activation model to experimentally test whether animals at high risk of developing a schizophrenia-like condition are more prone to acquire cocaine self-administration, show enhanced sensitivity to the reinforcing actions of cocaine or if they are resistant to extinction or vulnerable to relapse. Pregnant rats were injected with lipopolysaccharide (LPS) (2 mg/kg s.c.) or saline every other day during pregnancy, and the offspring was tested for sensorimotor gating (prepulse inhibition –PPI-). After this test, one group of rats was submitted to cocaine self-administration (0.5 mg/kg) under fixed and progressive ratio schedules, dose-response testing, extinction and cue-induced drug-seeking. Another group was sacrificed to study potential biomarkers in the immune blood cells by flow cytometry. While rats born to LPS-treated mothers showed impaired PPI, there were no differences in cocaine self-administration acquisition, responsiveness to dose shifts, extinction or cue-induced reinstatement. Finally, there were fewer DRD3+ granulocytes in the LPS-offspring and an exciting trend for CNR2+ lymphocytes to be more abundant in LPS-exposed rats. Our results indicate that the higher prevalence of cocaine abuse among people with schizophrenia is not due to a pre-existing pathology and suggest that DRD3+ granulocytes and possibly CNR2+ lymphocytes could be potential biomarkers of schizophrenia.</jats:p