Neonatal Anoxia Impacts Rats’ Maternal Behavior and Offspring Development due to Ultrasonic Vocalization’s Impairment

Abstract

Hypoxic-ischemic encephalopathy is a severe clinical condition, among others, affecting the brain after offspring exposure to neonatal anoxia, which causes persistent sensorimotor and cognitive deficits. During peripartum, maternal behaviors are crucial for the healthy development of the offspring. In rats, the vocalization of newborns, around 40 kHz, corresponds to separation calls that encourage their mothers to retrieve them. Alterations in this pattern affect the maternal behavior addressed to the offspring. This study aimed to evaluate the maternal behavior of primiparous rats whose offspring were exposed to neonatal Anoxia in P2 (postpartum day) during the lactation period, to assess mother-pup interactions through the pups' vocalization from P3 to P18. It also intends to quantify eventual neuronal alterations in the mothers' medial preoptic area (MPOA) after the last weaning (P21) through FOS protein expression. Anoxia offspring were found to reduce maternal behaviors towards them, increased frequency of separation calls in the male anoxia group, and reduced vocalization rate in the female anoxia group compared to their respective controls. Body weight gain reduction of males' and females' anoxia was observed. We concluded that anoxia exerts deleterious effects on the vocalization patterns of the pups, with sex differences that alter maternal behavior towards them. Impaired USV makes an additional negative impact on the already noxious effects of neonatal anoxia. Understanding those phenomena apply/contributes to guiding procedures and strategies to mitigate the deleterious outcomes and orient research concerning the complexity of neonatal anoxia events and the influence of maternal care quality concerning the pups, which should also be considered sex differences.

Pathophysiological aspects of neonatal anoxia and temporal expression of S100β in different brain regions

“…(2013) [4], astrocytes undergo a rapid period of maturation in the first postnatal weeks, which is marked by increased GFAP-positive cells, mainly in the hippocampal region. These data are corroborated by studies of our group which suggested a significant relationship between the hippocampus perinatal development, as well as the structures related to neurovegetative functions, in comparison to the cerebral cortex [3,5]; behavioral alterations in spatial memory [6]; neonatal vocalization [7], sex-dependent sensorimotor impairments [40,41] and metabolic disturbances [10].…”

“…The outcomes of this condition were explored in our laboratory with a neonatal anoxia model adapted and validated for rats [3] The anoxic stimulus used, by being global and noninvasive, simulates the preterm baby of 6 months who experienced lack of oxygen [3,4]. The research data found with this model revealed cell death, by necrosis and apoptosis in hippocampus [5]; behavioral alterations in spatial memory [6]; in neonates' vocalization [7]; and in nociceptive responses [8]; sex-dependent sensorimotor impairments [9], as well as metabolic disturbances due to the anoxic condition [10]. Among others, these results and the prevalence of the neonatal anoxic injury in neonatal clinics claims for research exploring suitable biomarkers along with strategies to avoid or minimize its deleterious effects.…”