Adolescent hyperactivity of offspring after maternal protein restriction during the second half of gestation and lactation periods in rats

Abstract

-To clarify the effect of systemic growth retardation on behavior, pregnant rats were fed a synthetic diet with either a normal (20% casein) or low (10% casein) protein concentration from gestational day 10 to postnatal day (PND) 21 at weaning. Offspring were examined for sensory and reflex functions, detailed clinical observations, manipulative test, grip strength, motor activity and water-filled multiple T-maze test. Lowering trend in the air righting reflex index during lactation period and a decrease in grip strength on PND 72 were observed in the low protein diet group showing suppression of systemic growth. However, they were simply the reflection of delayed systemic growth, because parameters on impaired reflex function, disturbance of motor function and paralysis were unaffected. On the other hand, low protein diet resulted in increased motor activity in female offspring. Thus, malnutrition due to maternal protein restriction may cause adolescent hyperactivity.

Programming the brain: Common outcomes and gaps in knowledge from animal studies of IUGR

“…Axonal density ↓ left hemispheric anxiety and memory pathways [117] Axonal degeneration + cingulate and somatosensory cortices, internal capsule, pontocerebellar tract [115] Microstructural reorganisation + [163] MYELINATION Cerebrum = [162] ↓ [117] Corpus callosum = [222] ↓ d60 [40] Cingulum ↓ d60 [112] Internal and external capsule = d60 [112] Astrogliosis Hippocampus ↑CA1 [113,115] Dentate gyrus ↑ [113,115] Entorhinal cortex ↑ [113,115] Cingulum ↑ [113,115] = [94] Fornix ↑ [113] Motor cortex = [115] Somatosensory cortex ↑ [115] Neonatal neurobehaviour = reflexes [79] ↓ righting reflex, d3-4 males, d3 females [87] ↓cliff avoidance, d7 females, d8, both sexes [87] ↓negative geotaxis, d7-8 males [87] = reflexes d10-21 [165] ↓surface righting, d2-9 ↓ negative geotaxis d 4-15 [129] ↓righting reflexes, locomotion, head turning and smell test scores as d1 neonates [116] Neuromotor ↓ grip strength adult males [165] ↓ motor learning, males [129] ↓motor learning, adults [222] Spatial learning = adult males [95] = adults [97,165] = adult males [167] ↓initial simple maze tests (lambs) [122] = extended simple maze testing, obstacle course tasks, tmaze tasks (lambs) [122] ↓initial simple maze tests (male lambs and young adults) [150] Revers...…”

“…Behavioural anxiety = male pups [79] =/↑ adult males [93,94] ↓ adults [98,216] ↑ reactivity to physical restraint and surprise, adults [84] ↑ adolescent females = adolescent males [131] ↑ adults [117] ↑ low birth weight female lambs [150] Spontaneous ambulation = adult males [94,95] ↑ females [165] ↑ in isolation tasks, adults [84] ↑ adults [113][114][115] ↓ adult males [160] ↓ Hyperactivity ↑ adult females [165] ↑adults [113][114][115] Exploratory behaviour ↑adult females [216] ↑adults [113][114][115] ↓ adults [117,163] Response to novelty ↓novelty seeking, adults [84] = adults [113] …”

“…Effects on fetal nutrient supply and metabolism also differ 164 between the various models of IUGR (Table 1). For example, fetal blood glucose does not appear to 165 be reduced by maternal protein restriction in rats [104,105], but is reduced in other models of 166 IUGR, such as utero-placental ligation in the guinea pig and in both utero-placental embolisation 167 and carunclectomy-induced placental restriction in sheep [11,[106][107][108][109][110][111]. 168 169 One particular limitation of models of maternal nutrient restriction in rodents is that the restriction 170 is imposed only during earlier stages of neurodevelopment than are affected by IUGR in humans.…”

Developmental programming of energy balance regulation: is physical activity more ‘programmable’ than food intake?

“…In this manner, the study demonstrated that maternal undernutrition during pregnancy caused reduced physical activity in the offspring shortly after weaning, and this persisted to adulthood. Two subsequent studies examined variants of another rat model of gestational undernutrition, assigning pregnant dams to a normal or low-protein diet during gestation ( 37 ) or gestation through weaning ( 38 ) . In the first study, offspring of control and undernourished dams were cross-fostered at birth to control dams to limit the exposure (undernutrition) to prenatal development.…”

“…Both male and female offspring of undernourished dams engaged in much less voluntary exercise than control offspring ( 37 ) . The other study of maternal low-protein diet ( 38 ) differed from the first in that the exposure started at day 10 of gestation and continued through the end of the suckling period. Rather than reduced physical activity, this study reported increased motor activity in adult (P72) offspring of undernourished dams.…”