TY - JOUR

T1 - Anoxia ameliorates the dexamethasone-induced neurobehavioral alterations in the neonatal male rat pups

AU - Menshanov, Petr N.

AU - Bannova, Anita V.

AU - Dygalo, Nikolay N.

N1 - Publisher Copyright: © 2016 Elsevier Inc.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Glucocorticoids and hypoxia are two essential factors affecting the brain development during labor and delivery. In addition to the neurobehavioral alterations induced separately by these factors, glucocorticoids can attenuate the deleterious consequences of severe hypoxia-ischemia on the brain development, acting as a neuroprotective agent in combination with hypoxia. The role of hypoxia in the combined action with corticosteroids is less clear. Severe hypoxia-ischemia results in the massive activation of caspase-3, masking any other effects of hypoxia on the neonatal brain exposed to glucocorticoids. As a result, the effects of mild hypoxia on the developing brain pretreated with glucocorticoids remain unclear. To analyze this problem, 2-day-old male rats were treated with dexamethasone (DEX) before the subsequent exposure to mild 10-min anoxia or normoxia. The treatment with only DEX resulted in the delay in the development of the negative geotaxis reaction and in the decrease in locomotor activity of the neonatal male pups. The mild anoxic event attenuated these DEX-induced neurobehavioral alterations. The treatment with DEX, but not the mild anoxic exposure alone, resulted in the delayed upregulation of active caspase-3 in the prefrontal cortex and in the brainstem of the male pups. This glucocorticoid-induced upregulation of active caspase-3 was prevented by the anoxic event. The present findings evidence that mild anoxia is capable of ameliorating the glucocorticoid-induced neurodevelopmental alterations in the neonatal rats if the artificial or the naturally occurring increase in the levels of glucocorticoids occurred just before the episode of hypoxia.

AB - Glucocorticoids and hypoxia are two essential factors affecting the brain development during labor and delivery. In addition to the neurobehavioral alterations induced separately by these factors, glucocorticoids can attenuate the deleterious consequences of severe hypoxia-ischemia on the brain development, acting as a neuroprotective agent in combination with hypoxia. The role of hypoxia in the combined action with corticosteroids is less clear. Severe hypoxia-ischemia results in the massive activation of caspase-3, masking any other effects of hypoxia on the neonatal brain exposed to glucocorticoids. As a result, the effects of mild hypoxia on the developing brain pretreated with glucocorticoids remain unclear. To analyze this problem, 2-day-old male rats were treated with dexamethasone (DEX) before the subsequent exposure to mild 10-min anoxia or normoxia. The treatment with only DEX resulted in the delay in the development of the negative geotaxis reaction and in the decrease in locomotor activity of the neonatal male pups. The mild anoxic event attenuated these DEX-induced neurobehavioral alterations. The treatment with DEX, but not the mild anoxic exposure alone, resulted in the delayed upregulation of active caspase-3 in the prefrontal cortex and in the brainstem of the male pups. This glucocorticoid-induced upregulation of active caspase-3 was prevented by the anoxic event. The present findings evidence that mild anoxia is capable of ameliorating the glucocorticoid-induced neurodevelopmental alterations in the neonatal rats if the artificial or the naturally occurring increase in the levels of glucocorticoids occurred just before the episode of hypoxia.

KW - Anoxia

KW - Brain

KW - Brainstem

KW - Caspase-3

KW - Cortex

KW - Development

KW - Dexamethasone

KW - Glucocorticoids

KW - Hypoxia

KW - Perinatal

KW - Animals, Newborn

KW - Up-Regulation/drug effects

KW - Neuroprotection

KW - Rats, Wistar

KW - Locomotion/drug effects

KW - Rats

KW - Male

KW - Glucocorticoids/adverse effects

KW - Brain/drug effects

KW - Prefrontal Cortex/drug effects

KW - Animals

KW - Behavior, Animal/drug effects

KW - Hypoxia/physiopathology

KW - Dexamethasone/adverse effects

KW - APOPTOSIS

KW - ENVIRONMENT

KW - HYPOXIA

KW - HIPPOCAMPUS

KW - ACTIVE CASPASE-3

KW - ISCHEMIC BRAIN-DAMAGE

KW - LABOR

KW - CEREBELLAR

KW - HYDROCORTISONE

KW - EXPRESSION

UR - http://www.scopus.com/inward/record.url?scp=84997079823&partnerID=8YFLogxK

U2 - 10.1016/j.yhbeh.2016.11.013

DO - 10.1016/j.yhbeh.2016.11.013

M3 - Article

C2 - 27865789

AN - SCOPUS:84997079823

VL - 87

SP - 122

EP - 128

JO - Hormones and Behavior

JF - Hormones and Behavior

SN - 0018-506X

ER -