Juvenile Exposure to BPA Alters the Estrous Cycle and Differentially Increases Anxiety-like Behavior and Brain Gene Expression in Adult Male and Female Rats.

Perinatal exposure to bisphenol A (BPA) in murine models has been reported to affect social behavior and increase anxiety. However, there is little information about the effects of BPA exposure during puberty, a period in which sex hormones influence the maturation and differentiation of the brain. In this work, we evaluated the effect of BPA administration during the juvenile stage (PND 21-50) on anxiety in male and female rats. Newly weaned Wistar rats were treated with BPA (0, 50, or 500 µg/kg/day) for 30 days. To compare the intra- and inter-sex behavioral profiles, rats were evaluated using four different anxiety models: the Open field test (OFT), the Elevated plus maze (EPM), the Light-dark box test (LDBT), and the Defensive burying test (DBT). Males exhibited a clear-cut anxious profile at both doses in all four tests, while no clear behavioral effect of BPA exposure was observed in female rats. The latter showed an altered estrous cycle that initiated earlier in life and had a shorter duration, with the estrous phase predominating. Moreover, the expression of ESR1, ESR2, GABRA1, GRIN1, GR, MR, and AR genes increased in the hippocampus and hypothalamus of male rats treated with 50 µg/kg, but not in females. Our results indicate that BPA consistently induces a higher anxiety profile in male than in female rats, as evidenced predominantly by an increase in passive-coping behaviors and changes in brain gene expression, highlighting the importance of sex in peripubertal behavioral toxicology studies.

Short-term memory reactivation of a weak CS-US association promotes long-term memory persistence in conditioned odor aversion.

In conditioned odor aversion (COA), the association of a tasteless odorized solution (the conditioned stimulus [CS]) with an intraperitoneal injection of LiCl (the unconditioned stimulus [US[), which produces visceral malaise, results in its future avoidance. The strength of this associative memory is mainly dependent on two parameters, that is, the strength of the US and the interstimuli interval (ISI). In rats, COA has been observed only with ISIs of ≤15 min and LiCl (0.15 M) doses of 2.0% of bodyweight, when tested 48 h after acquisition (long-term memory [LTM]). However, we previously reported a robust aversion in rats trained with ISIs up to 60 min when tested 4 h after acquisition (short-term memory [STM]). Since memories get reactivated during retrieval, in the current study we hypothesized that testing for STM would reactivate this COA trace, strengthening its LTM. For this, we compared the LTM of rats trained with long ISIs or low doses of LiCl initially tested for STM with that of rats tested for LTM only. Interestingly, rats conditioned under parameters sufficient to produce STM, but not LTM, showed a reliable LTM when first tested for STM. These observations suggest that under suboptimal training conditions, such as long ISIs or low US intensities, a CS-US association is established but requires reactivation in the short-term in order to persist in the long-term.

Cyclic changes and actions of progesterone and allopregnanolone on cognition and hippocampal basal (stratum oriens) dendritic spines of female rats.

Ovarian steroids modulate the neuronal structure and function during the estrous cycle, contrasting peak effects during the proestrus cycle and low effects during the metestrus cycle. An ovariectomy (OVX) decreases gonadal hormones and tests the effects of substitutive therapies. We studied female rats with a normal estrous cycle and we also studied the effects of systemic progesterone (P4, 4.0 mg/kg) or its reduced metabolite allopregnanolone (ALLO, 4.0 mg/kg, both for 10 days) in females who had had an OVX 16.5 weeks prior to the study (long-term OVX) with the novel object recognition test (NORT) for associative memory. The dendritic shape and spine density in Golgi-impregnated basal dendrites (stratum oriens) of hippocampal pyramidal neurons was also studied. Proestrus females had a better performance than metestrus or OVX females in short-term memory (tested 1 h after the acquisition phase). Proestrus and metestrus females showed better results than OVX females for long-term memory (24 h after the initial phase). Both P4 and ALLO recovered the cognitive impairment induced by long-term OVX. Also, proestrus females had a higher density of dendritic spines than metestrus females, OVX reduced the density of spines when compared to intact females, whereas both P4 and ALLO treatments increased the dendritic spine density, number of dendritic branches along the dendritic length, and branching order compared to vehicle. These data add the dendrites of the stratum oriens as an additional site for naturally occurring changes in spine density during the estrous cycle and evidence the actions of progestins in both behavioral recovery and the structural dendritic rearrangement of hippocampal pyramidal neurons in long-term OVX female rats.

Potencial antidiarreico in vitro, in vivo y antibacteriano de los extractos orgánicos de hoja, corteza y fruto de Vitex pyramidata B.L. Rob. (Lamiaceae) usada en la medicina tradicional mexicana / In vitro, in vivo and antibacterial antidiarrheal potential of the organic extracts of leaf, bark and fruit of Vitex pyramidata B.L. Rob. (Lamiaceae) used in traditional Mexican medicine

La diarrea es un trastorno sumamente frecuente en todo el mundo que sigue siendo causa frecuente de morbimortalidad en países en desarrollo, en particular en niños. La Organización Mundial de la Salud reporta que es uno de los cinco principales problemas de salud pública y la segunda causa de muerte infantil mundial. En México es la segunda causa de morbilidad y principal causa de consulta externa y hospitalaria en menores de cinco años. Los estudios etnobotánicos de plantas medicinales, pueden ser fuente de información para encontrar compuestos bioactivos, su uso ha hecho posible el desarrollo de un gran número de medicamentos para uso clínico. Una gran variedad de especies del género Vitex se usan como remedios por el pueblo mexicano y ha sido motivo de estudios en diversos países, aún así, solo 28 especies han sido estudiadas. El presente trabajo representa el primer estudio farmacológico de Vitex pyramidata utilizada en la medicina tradicional mexicana. Se evaluó el potencial antidiarreico in vitro, in vivo y antibacteriano de los extractos orgánicos hexánico, diclorometánico y metanólico de hoja, corteza y fruto. Se ensayaron los extractos en un modelo in vitro con intestino aislado de rata a una concentración de 150Sg/ml. Seis de los nueve extractos disminuyeron significativamente la frecuencia de los movimientos peristálticos. Tres de estos extractos: hexánico de hoja y los metanólicos de hoja y corteza, mostraron mayor actividad. En el modelo in vivo se analizaron estos tres extractos a una concentración de 250mg/kg, sin embargo no se encontraron diferencias significativas que pudieran considerarse relevantes. En las pruebas microbiológicas los extractos diclorometánico y metanólico de corteza, y hexánico y metanólico de hoja presentaron actividad. Las trece cepas bacterianas ensayadas fueron sensibles al menos frente a uno de estos extractos a una concentración máxima de 8 mg/ml, considerada como una actividad antibacteriana significativa, y nueve cepas presentaron inhibición a concentraciones menores o iguales a 2 mg/ml en al menos un extracto. Los resultados obtenidos en este estudio validan el conocimiento y uso medicinal tradicional que se tiene de V. pyramidata como antidiarreico.