The quantitative relationship between nutritional effects on preweaning growth and behavioral development in mice

Abstract

Our objective was to establish whether nutritional effects on the behavioral development of preweaning mouse pups were linearly related to effects on body and brain growth or whether there was a threshold effect, with behavior being affected only by nutritional extremes. We also used a standardized scale of development to compare the relative magnitude of such effects on morphological and behavioral measures. The level of nutrient availability was manipulated continuously by rearing the pups in litter sizes ranging from 3 to 12. On Day 32 post-conception, measures were taken of body weight, brain weight, thickness of the cerebellar external granular layer (EGL), and behavioral development. The relationship between litter size and body weight, brain weight, and behavioral development was best described by a linear regression model; no threshold effect was apparent. By comparing measures on animals from different litter sizes at the same age (32 days) to standard developmental curves over a wide range of ages, we found that for every additional pup in a litter, body growth was retarded by the equivalent of 1.28 days, brain weight by 0.44 day, and behavioral development by 0.07 day. Although the variation in nutrient availability provided by this range of litter sizes does result in a linear relationship between growth and behavioral development, there is nevertheless considerable sparing of function.

Advantages of mixed effects models over traditional ANOVA models in developmental studies: A worked example in a mouse model of fetal alcohol syndrome

“…The inverse relation seen in the untreated groups reflects the effects of normal variation in litter size on growth. As such, it is consistent with the findings of a previous study in which we varied litter size systematically and measured brain and behavioral development (Wainwright, Pelkman, & Wahlsten, 1989). However, in the ethanol groups, litter size is an indication of the effects of ethanol on pup survival, where the number of surviving pups is an indication of the overall severity of the treatment, that is, the smaller the litter, the more drastic the effects of the ethanol treatment on the remaining pups in the litter in terms of behavioral development and brain weight.…”

Assessment of Developmental Milestones in Rodents

“…That is to say that litters with fewer pups will have pups that weigh more, on average, than litters with larger numbers of pups. Wainwright et al (1989) showed that for every additional pup in a litter, body growth was retarded by the equivalent of 1.28 days, brain weight by 0.44 days, and behavioral development by 0.07 days. Therefore, it is sug-gested that litters of equal size be used whenever possible.…”

Timing and origin of the first cortical axons to project through the corpus callosum and the subsequent emergence of callosal projection cells in mouse

“…To describe the developmental stage of a mouse embryo or fetus, its chronological age (E16, for example) is conventionally used. However, because the prenatal growth rate of individuals varies substantially depending strongly on embryonic genotype and maternal environment (Wahlsten and Wainwright, 1977), the chronological age is not perfectly related to brain development (Wainwright et al, 1989). Previous studies have found that prior to birth, the body weight of a mouse is a better indicator of morphological maturity than age (Wahlsten and Smith, 1989;Bulman-Fleming and Wahlsten, 1991) and that more consistent results can be obtained by comparing brains of mice at the same body weight (Wahlsten, 1987;Wahlsten, 1992, 1993).…”