Ana Paula Lima

Zinc as a therapy in a rat model of autism prenatally induced by valproic acid

ABSTRACT Autism is characterized by numerous behavioral impairments, such as in communication, socialization and cognition. Recent studies have suggested that valproic acid (VPA), an anti‐epileptic drug with teratogenic activity, is related to autism. In rodents, VPA exposure during pregnancy induces autistic‐like effects. Exposure to VPA may alter zinc metabolism resulting in a transient deficiency of zinc. Therefore, we selected zinc as a prenatal treatment to prevent VPA‐induced impairments in a rat model of autism. Wistar female rats received either saline solution or VPA (400mg/kg, i.p) on gestational day (GD) 12.5. To test the zinc supplementation effect, after 1h of treatment with saline or VPA, a dose of zinc (2mg/kg, s.c.) was injected. The offspring were tested for abnormal communication behaviors with an ultrasound vocalization task on postnatal day (PND) 11, repetitive behaviors and cognitive ability with a T‐maze task on PND 29, and social interaction with a play behavior task on PND 30. Tyrosine hydroxylase protein (TH) expression was evaluated in the striatum. Prenatal VPA decreased ultrasonic vocalization, induced repetitive/restricted behaviors and cognitive inflexibility, impaired socialization, and reduced striatal TH levels compared with control group. Zinc treatment reduced VPA‐induced autistic‐like behaviors. However, we found no evidence of an effect of zinc on the VPA‐induced reduction in TH expression. The persistence of low TH expression in the VPA‐Zn group suggests that Zn‐induced behavioral improvement in autistic rats may not depend on TH activity.

Beta-adrenergic antagonist prevents anxiety like behavior and natural killer cells migration to the spleen in a model of cohabitation with sick partners

Cohabitation for 11 days with two Ehrlich tumor bearing-mice: two mice from control group were treated with vehicle (experimental day 1) and the other mouse was kept undisturbed (companion of health partner). Between ED6 and ED11, CHP were treated with vehicle or propranolol. Two mice from experimental group were inoculated with Ehrlich tumor cells i.p. and the other was kept undisturbed (companion of sick partner). Between ED6 and ED11, CSP were treated with vehicle or propranolol. During psychological stress, catecholamines produced by the sympathetic nervous system (SNS) regulate the immune system and cohabitation for 11 days with two Ehrlich tumor bearing-mice induces psychological stress. Besides, the aversive effects in cohabitation with sick partners are related with the release of odor cues. After cohabitation with sick companions the open field test was used to measure behaviors characteristic of anxiety and indicated that the cohabitation increase in anxiety-like behavior was blocked by pre-treatment with the beta-adrenergic antagonist propranolol. Pre-treatment with the beta-adrenergic antagonist propranolol did not significantly alter corticosterone levels indicating no difference in activation of the hypothalamic-pituitary-adrenal (HPA) axis. Likewise propranolol pre-treatment abrogated the migration of natural killer (NK) cells to the spleen. Collectively, these data suggest that behavioral and immune changes in the model of cohabitation with sick partners occur through beta-adrenergic dependent signaling.