IMPACT OF MOTHER RAT’S PHYSIOLOGICAL STRESS RESPONSE ON OFFSPRING’S BODY WEIGHT 1 Department of Psychology and 2 Department of Neuroscience, University of New Mexico, Albuquerque, NM, USA Zhen Yang 1, Bethany C. Reeb 1, & Akaysha C. Tang 1,2 METHODS INTRODUCTION Neonatal Novelty Exposure REFERENCES DISCUSSION 1.Tang, A., Akers, K.G., Reeb, B.C., Romeo, R.D., & McEwen, B.S. (2006). Programming social, cognition, and neuroendocrine development by early exposure to novelty. PNAS, 103(42), Meaney, M.J., Aitken, D.H., Berkel, C.V., Bhatnagar, S., & Sapolsky, R.M. (1988). Effect of neonatal handling on age-related impairments associated with the hippocampus. Science, 239: Denenberg, V.H. (1997). Commentary: Is maternal stimulation the mediator of the handling effect in infancy? Developmental Psychobiology, 34 (1): Parker, K.J., Buckmaster, C.L., Sundlass, K., Schatzberg, A.F., & Lyons, D.M. (2006). Maternalmediation, stress inoculation, and the development of neuroendocrine stress resistance in primates, PNAS, 103: Benetti, F., de Araujo, P.A., Sanvitto, G.L., & Lucion, A.B. (2007). Effects of neonatal novelty exposure on sexual behavior, fear, and stress-response in adult rats. Developmental Psychobiology, 49 (3) : Panagiotaropoulos, T., Papaioannou, A., Pondiki, S., Prokopiou, A, et al. (2004). Effect of neonatal handling and sex on basal and chronic stress-induced corticosterone and leptin secretion. Neuroendocrinology, 79 (2): Silveira, P.P., Benetti, C.S., Ayres, C., Pederiva, F.Q., Portella, A.K., et al (2006). Satiety assessment in neonatally handled rats. Behavioural Brain Research, 173: male Long-Evans hooded rats from 14 litters. Animals RESULTS 1.Effect of neonatal novelty exposure was modulated by maternal physiological stress response (a)All 4 measures combined: F(1, 12)= , p = 0.027, f=0.729 (b)At weaning: F(1, 12)= , p = 0.004, f=1.012; (c)At Day 100: F(1, 12)=0.120, p=0.735, f= (d)12 month: F(1, 11)= 6.812, p = 0.024, f=0.786; (e)13 month: F(1, 12)= 4.161, p = 0.032, f=0.588 ; Using the rat as a model system for understanding cognitive and social development, we (Tang et al., PNAS 2006) and others (Meaney et al Science 1988) have found that seemingly mild neonatal stimulation can have long lasting impact on the adult offspring’s spatial and social memory and that these long-term impact involve changes in the stress response system. While the phenomenon of early stimulation effects is firmly established, the relative roles played by direct stimulation effects and maternal influence continue to receive heated debate (Denenberg, Dev Psychobio 1999; Parker et al., PNAS 2006; Tang et al., PNAS 2006; Benetti et al., Dev Psychobio 2007). Here using the adult-offspring body weight as an index for physical development, we aimed to test the hypothesis that maternal physiological stress response modulates the effect of neonatal stimulation on offspring’s body weight. We tested this hypothesis by exposing infant pups to a relatively novel non-home environment (neonatal novelty exposure) during the first 3 weeks of life and making multiple measures of body weight across life span. We found that effect of neonatal novelty exposure on offspring’s body weights is modulated by characteristics of their mother’s stress response profile. Weight measurements Data analysis Experiment Timeline From postnatal day 1-21, one half of a litter was exposed to a novel environment (N: Novel) for 3 min daily, while the rest of the litter remained in the home cage (H: Home) (split-litter design). Amount of experimenter handling was matched between N and H pups (Tang et al 2003). 1.Weaning: On PND 22, animals were weighed litter- by-litter as they were weaned between 2-6pm. 2. Day 100: On PND100, animals were weighed litter-by- litter between 2-3:30 pm Month: At 12 months of age, animals were weighed twice on 2 consecutive days to obtain an average weight measure. Daily food consumption was measured to partial out its contribution to the weight measure Month: At 13 month of age, animals were weighed once after 15 hours of food and water restriction to minimize weight variations due to food and water intake For each weight measure, a novelty effect score (NE) was computed for each litter: NE = Novel Litter Average Home Litter Average – Measure of Maternal Stress Response Basal level of corticosterone (CORTb) was measured 1 day before swim stress and stress level of corticosterone (CORTe) was measured at 5 min following 1-min swim stress. Maternal CORT stress response: CORTe – CORTb CORTb × Effect of neonatal novelty exposure at weaning does not predict those at adulthood but those at adulthood predict each other 3. Early weight predicts subsequent weight and predictive power decreases over time. Centered CORT increase Average CORT increase –= Analysis of Covariate (ANCOVA) 1. Litter-based analysis was used to reduce variations due to litter effect,. 2. Data were ranked due to heterogeneity of variance in the raw data. 3. Maternal stress response measure was centered: 4. Repeated measures ANCOVA was used on all four weight measures with Novelty as a within factor and maternal centered CORT as a covariate. In 12 month, food consumption was also taken as a covariate to partial out the influence of food intake. Correlations 1. Due to heterogeneity of variance in the raw data, NE and weights were cubic root transformed. 2. Correlations between all pairs of NEs and all pairs of weight measures were computed. Litter and group effects were partial out. r=.526, p=.053 r=-.005, p=.987 r=.309, p=.283 r=.056, p=.848 r=.526, p=.053 r=.810, p=.000 Cubic root transformed NE (g) weaning day month 13 month Cubic root transformed NE (g) r=.319, p=.012 r=.500, p=.000 r=.337, p=.007r=.693, p=.000 r=.617, p=.000r=.971, p=.000 weaningday month day month 13 month Cubic root transformed weight (g) 1.Effect of the neonatal novelty exposure on offspring body weight depends on maternal stress response profile. 2.If the mother can mount a rapid response to a stressor, then the offspring receiving early stimulation will weigh more than those without such stimulation. 3. If the mother mounts a sluggish stress response, the offspring receiving early stimulation will weigh less than those without stimulation. 4. This maternal modulation of body weight is greatest at weaning, absence around the onset of the adulthood, and re-emerges at later adulthood. 5. This discontinuity in maternal modulation is mirrored by a similar discontinuity in correlations between early stimulation effects on multiple points in time. 6. No uniform effect of neonatal stimulation on body weight was found. This is consistent with inconsistent literature which reports neonatal handling both increasing (Panagiotaropoulos, et al, Neuroendo, 2004) and having on effects (Silveira, et al, Behav. Brain Res., 2006) on body weights. D1-21 Maternal CORT D moPND22 Weight 1 13mo Weight 3Weight 4Weight 2 D100 Novelty Exposure 13 Month 12 month Day 100 Weaning Raw NE Score (g) Maternal CORT Stress Response (rank, % increase) Ranked NE Score Home Novel Home Novel Home Novel Home Novel Weight (rank)