Maternal Hyperglycemia Leads to Gender-Dependent Deficits in Learning and Memory in Offspring

Abstract

Pregnancy in the diabetic woman has long been associated with an increased risk of congenital malformation in the offspring. However, little is known about the effects of maternal diabetes on development of the central nervous system. To begin to gain an understanding of this problem, diabetes was induced in adult female Sprague-Dawley rats by injection with streptozotocin. Only animals with serum glucose levels greater than 200 mg/dl were used. Diabetic and control females were bred, and all newborn pups were cross-fostered to nondiabetic mothers. At 60 days of age, pups were tested in an elevated plus-maze to assess differences in emotionality and anxiety. There were no significant differences between offspring of diabetic dams and controls on this measure. All pups were then housed individually, put on food restriction, and maintained at 85% of their ad libitum weight. They were then trained in a Lashley III maze, which assesses learning and retention capability. The female offspring of diabetic dams performed poorer than controls, a finding that was supported by inhibitory avoidance data from a separate group of animals. All animals were then trained in a radial-arm maze. Results failed to find differences between experimental and control animals. It was concluded that the diabetic intrauterine environment has gender-specific effects on central nervous system development.

Chronic maternal hyperglycemia induced during mid-pregnancy in rats increases RAGE expression, augments hippocampal excitability, and alters behavior of the offspring

“…We also noted an apparent increase in preference for novel location in the object-place paradigm without significant effects in object recognition memory. Previous studies have noted impairments in learning and memory in some paradigms, including the Lashley III maze and inhibitory avoidance paradigm in the offspring of dams diabetic for the entire pregnancy (Kinney et al, 2003). Interestingly, these effects were more pronounced in females.…”

“…Previous studies have noted increased anxiety-like behavior (Ramanathan et al, 2000) and no change in behavior on the elevated plus maze (Kinney et al, 2003) in the offspring of diabetic dams. However, in these previous studies, the dams were rendered diabetic before breeding.…”

“…When the long-term effects of maternal diabetes during pregnancy on the offspring are considered, a range of behavioral, neurochemical, and molecular abnormalities are observed (Boksa, 2004;Van Lieshout and Voruganti, 2008;Jawerbaum and White, 2010). Increased anxiety-like behavior, reduced social interaction, and impaired learning and memory (female offspring only) have been reported in the offspring of dams treated with STZ (Ramanathan et al, 2000;Kinney et al, 2003). Elevated levels of dopamine and norepinephrine in the hypothalamus (Plagemann et al, 1998) and decreased brain weight (Yamano et al, 1986) have also been reported in the offspring of STZ-treated dams.…”

Maternal-Fetal Outcome, Lipid Profile and Oxidative Stress of Diabetic Rats Neonatally Exposed to Streptozotocin

“…Animal models of experimentally induced hyperglycemia are helpful for specifi cally studying the long-range eff ects of maternal hyperglycemia on off spring. Among the models used in animals for hyperglycemia induction during pregnancy, STZ administration prior to pregnancy ( Eriksson et al, 1982 ;Caluwaerts et al, 2003 ;Kinney et al, 2003 ), during pregnancy ( Oh et al, 1991 ;Gelardi et al, 1990 Introduction ▼ Diabetic pregnancy causes reproductive abnormalities that enhance spontaneous abortion, congenital anomalies, and neonatal morbidity and mortality ( Van Assche et al, 1998 ; Eriksson et al, 2003 ). The high rate of birth defects associated with diabetic pregnancy is a signifi cant public health problem that results in congenital malformations in up to 10 % of newborn babies.…”

Consequences of gestational diabetes to the brain and behavior of the offspring

“…Studies which directly investigated whether intra-uterine exposure to hyperglycemia and hyperinsulinemia were associated to altered anxiety levels showed confounding results. While some of them report no differences in anxiety levels among rats born from GD dams when diabetes was induced before pregnancy (Kinney et al 2003, Ramanathan et al 2000, one study reported decreased anxiety levels in the offspring when STZ was administered during mid pregnancy (Chandna et al 2015), a condition which more closely resembles the time course of GD development in humans.…”