HDAC2 Inhibits Hippocampal Neurogenesis and Impairs the Cognitive Function in Prenatally Stressed Adult Offspring / HDAC2 Inhibe la Neurogénesis del Hipocampo y Afecta la Función Cognitiva en la Descendencia Adulta Estresada Prenatalmente

SUMMARY: The objective of this study was to investigate the mechanism of prenatal stress on the cognitive function of offspring, and clarify the change of histone deacetylase 2 (HDAC2) expression in hippocampal neurons of offspring. 16 pregnant SD rats were randomly divided into control group and stress group, with eight rats in each group. The stress group received restrained stress from 15 to 21 days of pregnancy, while the control group did not receive any treatment. Anxiety-like behavior and spatial memory, learning and memory ability were detected in open field, elevated plus maze, novel object recognition test, and Barnes maze. Nissl staining was used to detect the function of hippocampal neurons. Western blot was used to detect the expression of HDAC2 protein in hippocampal neurons of adult offspring. Immunofluorescence staining was used to detect the expression of HDAC2 protein and hippocampal neurogenesis. The learning and memory ability of adult offspring was decreased. The prenatal stress damaged the function of hippocampal neurons , the expression of HDAC2 was down-regulated, and the number of neurons was reduced. Maternal prenatal stress can down- regulate the expression of HDAC2 in the hippocampus of offspring, inhibits hippocampal neurogenesis and impairs the cognitive function.

El objetivo de este estudio fue investigar el mecanismo del estrés prenatal en la función cognitiva de la descendencia y aclarar el cambio de la expresión de la histona desacetilasa 2 (HDAC2) en las neuronas del hipocampo de la descendencia. 16 ratas SD preñadas se dividieron aleatoriamente en un grupo de control y un grupo de estrés, con ocho ratas en cada grupo. El grupo de estrés recibió estrés durante 15 a 21 días de pre, preñez, mientras que el grupo de control no recibió ningún tratamiento. El comportamiento similar a la ansiedad y la memoria espacial, el aprendizaje y la capacidad de memoria se detectaron en campo abierto, laberinto en cruz elevado, prueba de reconocimiento de objetos novedosos y laberinto de Barnes. La tinción de Nissl se utilizó para detectar la función de las neuronas del hipocampo. Se utilizó Western blot para detectar la expresión de la proteína HDAC2 en las neuronas del hipocampo de la descendencia adulta. La tinción de inmunofluorescencia se utilizó para detectar la expresión de la proteína HDAC2 y la neurogénesis del hipocampo. La capacidad de aprendizaje y memoria de la descendencia adulta se redujo. El estrés prenatal dañó la función de las neuronas del hipocampo, se reguló negativamente la expresión de HDAC2 y se redujo el número de neuronas. El estrés prenatal materno puede regular a la baja la expresión de HDAC2 en el hipocampo de la descendencia, inhibe la neurogénesis del hipocampo y deteriora la función cognitiva.

Neurobehavioral assessment of Danio reriointoxicated by Mercury and the use of Mercurius solubilis

Mercury is used in various industrial. Part of Mercury's industrial waste is discharged into the environment, rivers and their tributaries, thus contaminating aquatic animals. Aim:to evaluate Mercury-induced behavioral changes in Zebrafish (Danio rerio) by the analysis of locomotor activity and parameters related to neurotoxicity and to verify whether ultra-diluted substances can decrease neurobehavioral effects and toxic. Methodology:The fishes were separated into 4 monitoring aquariums with 8 fishes each, with temperature, pH controlled, until the time of the toxicological experiments. 0.5 mL of Mercury 6cH, 30cH and distilled water (positive control) were added per liter of water in each aquarium containing 6 liters of water, then 3 mL of medication per aquarium, the white control received no medication and the toxic agent. After 1 hour the drugs were added, toxic mercury (200 µg/L), 4 mL per aquarium was added and remained so for 24 hours. All the experiment was run in blind, and the drugs identified by codes. The animals were subjected to behavioral tests (Open Field-locomotion; Vertical Open Field for neurotoxicity evaluation and Light and Dark Test), and each stage was recorded for later evaluation of movements and neurobehavioral changes. ANOVA was performed, followed by Tukey test, with p <0.05. Results: Mercury produced an anxiogenic effect in animals that were submitted to it without medication. In the vertical open field, there was an increase in erratic movements (1.25 ± 1.0) and tremors (0.87 ± 0.35) compared to the control (0.12 ± 0.35 and 0.25 ± 0.46 respectively), proving the toxic effect. Fishes which received the medication at 6 cH and 30 ch showed tremors and erratic movements similar to control. Conclusion:200 µg/L mercury in water can cause neurobehavioral disturbances in fishes, and animals receiving Mercurius6 cH and 30 cH ultra-diluted drug did not show neurotoxicity.

Antidepressant-like effect of caffeic acid: Involvement of the cellular signaling pathways

Abstract Caffeic acid is a phenolic compound widely distributed in plants and beverages such as coffee. Although its mechanism of action is poorly understood, caffeic acid reportedly induces antidepressant-like and neuroprotective effects. This study aimed to investigate the involvement of cellular signaling pathways in acute antidepressant-like effect induced by caffeic acid in mice. All procedures were approved by the Institutional Animal Ethics Committee of the UNIVALI n. 021/2013. Female Swiss mice were administered with vehicle, caffeic acid (5 mg/ kg, p.o.), inhibitor (H-89, U0126, chelerythrine, or PD9859, i.c.v.) or caffeic acid plus inhibitor. The behavioral effects were evaluated 1h after the administration of compounds to mice using tail suspension test (TST) and open field test (OFT). The results showed that the antidepressant- like effect of caffeic acid in mice was possibly mediated by the activation of PKA, MEK 1/2, PKC and MAPK (as assessed using TST), without compromising their locomotor activity (as assessed using OFT). Our results demonstrated, at least in part, the pathways involved in the neuroprotective and behavioral effects of caffeic acid.

Behavioral characterization of ayahuasca treatment on Wistar rats in the open field test

Abstract Ayahuasca (AYA) is a psychedelic beverage with therapeutic potential for many mood and anxiety disorders. Although there are some preclinical studies, no published reports have tested the behavioral effects of AYA gavage in animal models. This investigation aimed to characterize the behavior of Wistar rats after acute ingestion of AYA for 40 min in the open field test (OFT). The sample consisted of three experimental groups treated with different dosages of AYA (125, 250, or 500 mg kg-1) and a control group. Each group consisted of 10 participants. After gavage, the number of crossings of the OFT grid lines, latency to enter the central area of the device, grooming frequency, and time spent in the central perimeter of the device were immediately evaluated. Analyses were based on one-way ANOVA and a linear-regression mixture model for longitudinal data. AYA intake did not interfere with habituation. The 500 mg kg-1 group showed a decrease in the time spent in the center of the device and in the number of crossings compared to the control group in the last 10 min. These results suggest that gavage with AYA did not interfere with the results, and the behavioral effects were perceived only between 30 and 40 min after gavage. Taken together, the results indicate that three aspects should be considered in OFT studies of AYA acute effects: the moment when the observation starts, the observation period, and the AYA dosage.

Evaluation of subchronic formaldehyde exposure in rats with open field test / Evaluación de la exposición al formaldehído subcrónico en ratas con prueba de campo abierto

SUMMARY: Formaldehyde (FA), which is an indispensable chemical substance in anatomy and pathology, is a very harmful substance for living things. In our study, the purpose was to investigate the changes in behavior of rats exposed to subchronic formaldehyde with open field test. We divided 24 Wistar-Albino rats into 3 groups. The first group (n=8) was identified as the control group, and normal air breathing was ensured. Low-dose FA (mean 1 ppm) was inhaled in the second group, and high-dose FA (mean 10 ppm) was inhaled in the third group. FA exposure was done for 4 hours, 12 weeks, and 5 days a week. The rats were subjected to open field test during the first week and the last week of FA exposure. We observed significant decreases in the number of vertical movements and grooming in rats in the experimental group compared to the control group in the open field test (p 0.05). As a conclusion, we can argue that FA causes changes in the behaviors of rats regardless of dose and duration.

RESUMEN: El formaldehído (FA), una sustancia química indispensable en la anatomía y patología, pero es un elemento sumamente nocivo para todos los seres vivos., El objetivo de nuestro estudio fue investigar los cambios en el comportamiento de ratas expuestas a formaldehído subcrónico con prueba de campo abierto. Utilizamos 24 ratas Wistar-Albino divididas en 3 grupos. El primer grupo (n = 8) se identificó como el grupo de control y se aseguró una respiración normal de aire. En el segundo grupo se inhalaron dosis bajas de FA (media de 1 ppm) y en el tercer grupo se inhalaron dosis altas de FA (media de 10 ppm). La exposición a FA se realizó durante 4 horas, 12 semanas y 5 días a la semana. Las ratas fueron sometidas a una prueba de campo abierto durante la primera semana y la última semana de exposición a FA. Observamos disminuciones significativas en el número de movimientos verticales y acicalamiento en ratas en el grupo experimental en comparación con el grupo control en la prueba de campo abierto (p 0,05). Como conclusión, podemos argumentar que la AF provoca cambios en el comportamiento de las ratas independientemente de la dosis y la duración.

Efeitos do enriquecimento ambiental sobre padrões de comportamento e ansiedade no Status Epilepticus / Effects of environmental enrichment on behavioral and anxiety no Status Epilepticus

Introdução: O Enriquecimento ambiental (EA) tem sido estudado em reabilitação para diversas patologias. Objetivo: investigar os efeitos do EA em ratos wistar jovens submetidos ao status epilepticus, sobre os padrões de comportamento e ansiedade. Métodos: Estudo longitudinal com 40 ratos, submetidos às crises no 15º dia e enriquecimento ambiental e, posteriormente, aos testes labirinto em cruz elevado e campo aberto. Utilizou-se o teste ANOVA two-way, considerando como significante valor de p<0,05. Resultados: No teste do labirinto houve relação entre levantar em duas patas (p<0,01), comportamento de risco (p<0,01) tempo nos braços abertos (p<0,01), número de entradas nos braços fechados (p<0,01), tempo nos braços fechados (p<0,01) e o número de cruzamentos no campo aberto (p=0,01) com status epilepticus. Não houve relação entre os testes e o EA. Conclusão: O EA não reverteu os padrões de ansiedade e comportamento afetados pelo status epilepticus. (AU)

Background: Environmental Enrichment (EE) has been studied in rehabilitation for several pathologies. Objective: to investigate the effects of EE on young wistar rats submitted to status epilepticus, on behavior and anxiety patterns. Methods: Longitudinal study with 40 rats, submitted to seizures on the 15th day and environmental enrichment, and later to the labyrinth tests in high cross and open field. The two-way ANOVA test was used, considering a significant value of p <0.05. Results: In the labyrinth test, there was a relationship between two paws (p <0.01), risk behavior (p <0.01) in open arms (p <0.01), number of entries in closed arms (p <0.01), time in the closed arms (p <0.01) and the number of crosses in the open field (p = 0.01) with status epilepticus. There was no relationship between the tests and the EE. Conclusion: The EE did not reverse the behavior and anxiety patterns affected by the status epilepticus. (AU)