Prenatal hypoxia modifies working memory and the activity of hippocampal polyphosphoinositide system in rats

Abstract

The aim of the present study was to explore spatial learning abilities in the Morris water maze (working memory) as well as hippocampal levels of phosphatidylinositol 4,5-diphosphates (TPI), phosphatidylinositol 4-phosphates (DPI), phosphotidylinositols (MPI), and expression of the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) in rats exposed to severe hypobaric hypoxia (ascent to 11 km, 3 h) on prenatal days 14-16 (group 1) or 17-19 (group 2). Exposure to severe hypoxia led to significant elevation of TPI and DPI hippocampal levels in juvenile and adult rats in group 1, however these changes were more pronounced in juvenile rats than in adults. In group 2, hypoxia upregulated TPI and DPI hippocampal levels in juvenile rats, but in adult animals of this group only a small TPI level upregulation was detected. Activation of IP3R1 expression was found to occur in the hippocampus both of juvenile and adult rats in groups 1 and 2. These data are consistent with our findings on impaired spatial learning ability in the Morris water maze indicative of a working memory deficit in the rat offspring exposed to hypobaric hypoxia during the first half of the last week of pregnancy.

Role of Prenatal Hypoxia in Brain Development, Cognitive Functions, and Neurodegeneration

“…For example, various types of rat memory (working, short and long-term memory) assessed by 8-arm maze and novel object recognition were compromised and correlated with the structural changes observed in the hippocampus (Zhuravin et al, 2011 ; Nalivaeva et al, 2012 ; Cunha-Rodrigues et al, 2018 ). Some studies link working memory impairment observed both in juvenile and adult rats subjected to prenatal hypobaric hypoxia with increased levels of phosphatidylinositol 4,5-diphosphates and phosphatidylinositol 4-phosphates in the hippocampus and upregulated expression of the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) (Tyul'kova et al, 2015 ). Maternal hypoxia on days 15–21 was shown to result in increased activity of metalloproteinases and significant cell death in the hippocampus of rat pups on days 0–7 after birth, which correlated with worsened development of their neurobehavioral functions (Tong et al, 2010 ).…”

Prenatal hypoxia–ischemia decreases spatial memory and increases aggression during adolescence

“…The degeneration and necrosis in the prefrontal cortex and hippocampus were observed to be proportional with the duration of HI (4). A study by Dubrovskaia and Zhuravin (9) on rats revealed that prenatal HI during embryonic days 14 and 18 impaired short-and long-term memory, as shown in other studies (13,19,30). Chronic prenatal HI condition has been considered to be associated with the disruption in neuron production during the late fetal life, but this effect did not last until the postnatal period (28).…”