RESUMO
Individuals with post-traumatic stress disorder (PTSD) show increased rates of several serious metabolic diseases. However, little is known about pre-existing metabolic diseases and the development of PTSD. Therefore, we aimed to evaluate the course of post-traumatic stress disorder (PTSD) development in rats with preexisting diabetes. In addition, we quantified glial fibrillary acidic protein (GFAP) in the hippocampus of the experimental animals. For this, we used male Wistar rats and divided them into two groups: saline and alloxan (150 mg/Kg, i.p.). The animals were weighed, and plasma glucose was measured after 48 h of diabetes induction by alloxan. The animals were either exposed to inescapable footshocks or not, followed by social isolation. After 14 days, the animals were re-exposed to the box, and the freezing time was evaluated for 10 min. Over the following days, the animals were tested on the open field, social interaction and forced swimming tests. In another group of animals, elevated plus maze and object recognition tests were performed. Our results demonstrated that animals with diabetes had more pronounced PTSD-like symptoms as a reduction in social interaction, an increase in immobility time in forced swimming, a reduction in permanence in the open arms of the elevated plus maze, and a deficit in the object recognition index more accentuated. However, this did not reflect astrocyte activation in the hippocampus. In conclusion, diabetes accentuates post-traumatic stress disorder-like symptoms but not astrocyte activation in the hippocampus.
Assuntos
Astrócitos/metabolismo , Diabetes Mellitus Experimental/metabolismo , Hipocampo/metabolismo , Transtornos de Estresse Pós-Traumáticos/metabolismo , Animais , Diabetes Mellitus Experimental/complicações , Proteína Glial Fibrilar Ácida/metabolismo , Masculino , Ratos , Ratos Wistar , Transtornos de Estresse Pós-Traumáticos/complicaçõesRESUMO
AIMS: We assessed the influence of maternal overweight on the behavioral neurodevelopment of male and female offspring in prepubertal age by reducing the litter size. MAIN METHODS: To reduce litter size in Wistar rats, the offspring of generation 0 (G0) were culled for 12 pups (6 males and 6 females: normal litter, NL-G1) or 4 pups (2 males and 2 females: small litter, SL-G1). In G1 dams, overweight was characterized, maternal behavior and locomotor activity were assessed. At G2, we quantified the ultrasonic vocalizations in post-natal day 5 (PND5); we evaluated olfactory discrimination in the homing behavior test on PND13; and in PND28-32 (prepubertal age), we performed the following tests: social play behavior, hole board, object recognition, and open field. At the end of the experiments, hippocampus and prefrontal cortex were dissected to quantify the synaptophysin by western blotting. KEY FINDINGS: Our data demonstrated that a reduction in litter size was able to induce maternal overweight without altering the parameters related to overweight in the offspring. The SL-G2 offspring showed deficits in early social communication, olfactory discrimination, social play behavior, and the exploration of objects, in addition to increasing repetitive and stereotyped movements. There were also changes in the synaptophysin levels in the hippocampus and prefrontal cortex of the offspring from reduced litter dams. In conclusion, maternal overweight caused by litter reduction impairs behavioral neurodevelopment, inducing autism-like symptoms in the offspring. SIGNIFICANCE: This study alerts the public about the negative consequences of maternal overweight in the descendants.
Assuntos
Comportamento Materno/fisiologia , Transtornos do Neurodesenvolvimento/etiologia , Sobrepeso/fisiopatologia , Animais , Animais Recém-Nascidos , Peso Corporal , Encéfalo/metabolismo , Feminino , Hipocampo/metabolismo , Tamanho da Ninhada de Vivíparos/fisiologia , Masculino , Transtornos do Neurodesenvolvimento/fisiopatologia , Fenômenos Fisiológicos da Nutrição/fisiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos WistarRESUMO
Exposure to stressful environmental events during the perinatal period can increase vulnerability to psychopathologies that cause neuroendocrine changes associated with deficits in emotional behavior that can appear early in life. Post-traumatic stress disorder (PTSD) is a frequent, chronic, and disabling disorder that negatively impacts the emotional, social, and cognitive behaviors of affected individuals. Thus, we induced PTSD in pregnant rats by applying inescapable footshocks and then investigated the behavioral parameters similar to anxiety in offspring at prepubertal age, in addition to the plasma levels of maternal and offspring corticosterone and expression of glucocorticoid receptors (GR) in the offspring's hippocampus. With the dams, maternal behavior, open field, and object recognition tests were performed. With the male and female offspring, we performed the following: quantification of ultrasonic vocalizations, elevated plus-maze test, evaluation of exploratory activity in the open field, and hole board test, as well as plasma corticosterone measurements and Western blotting for GR. Our results showed that gestational PTSD affected maternal behavior, led to anxiety-like symptoms, increased corticosterone levels, and increased GR expression in the offspring's hippocampus. Therefore, our data can contribute to the understanding of the onset of early (childhood and juvenile/pre-pubertal phases) anxiety owing to exposure to a traumatic event during the gestation period.