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Moderate recurrent hypoglycemia during early development leads to persistent changes in affective behavior in the rat.

ABSTRACT: Recurrent hypoglycemia is a common problem among infants and children that is associated with several metabolic disorders and insulin-dependent diabetes mellitus. Although studies have reported a relationship between a history of juvenile hypoglycemia and psychological health problems, the direct effects of recurrent moderate hypoglycemia have not been fully determined. Thus, in this study, we used an animal model to examine the effects of recurrent hypoglycemia during the juvenile period on affective, social, and motor function (assessed under euglycemic conditions) across development. To model recurrent hypoglycemia, rats were administered 5 U/kg of insulin or saline twice per day from postnatal day (P)10 to P19. Body weight gain was retarded in insulin-treated rats during the treatment period, but recovered by the end of treatment. However, insulin-treated rats displayed increases in affective reactivity that emerged early during treatment and persisted after treatment into early adulthood. Specifically, insulin-treated pups showed increased maternal separation-induced vocalizations as infants, and an exaggerated acoustic startle reflex as juveniles and young adults. Moreover, young adult rats with a history of recurrent juvenile hypoglycemia exhibited increased fear-potentiated startle and increases in behavioral and hormonal responses to restraint stress. Some of these effects were sex-dependent. The changes in affective behavior in insulin-exposed pups were accompanied by decreases in adolescent social play behavior. These results provide evidence that recurrent, transient hypoglycemia during juvenile development can lead to increases in fear-related behavior and stress reactivity. Importantly, these phenotypes are not reversed with normalization of blood glucose and may persist into adulthood.

SUBMITTER: Moore H

PROVIDER: S-EPMC2885529 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Moderate recurrent hypoglycemia during early development leads to persistent changes in affective behavior in the rat.

Moore Holly H Craft Tara K S TK Grimaldi Lisa M LM Babic Bruna B Brunelli Susan A SA Vannucci Susan J SJ

Brain, behavior, and immunity 20091126 5

Recurrent hypoglycemia is a common problem among infants and children that is associated with several metabolic disorders and insulin-dependent diabetes mellitus. Although studies have reported a relationship between a history of juvenile hypoglycemia and psychological health problems, the direct effects of recurrent moderate hypoglycemia have not been fully determined. Thus, in this study, we used an animal model to examine the effects of recurrent hypoglycemia during the juvenile period on aff ...[more]

PMID: 19944751

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Project description:Diet has been shown to have a significant impact on microbial community composition in the rumen and could potentially be used to manipulate rumen microbiome structure to achieve specific outcomes. There is some evidence that a window may exist in early life, while the microbiome is being established, where manipulation through diet could lead to long-lasting results. The aim of this study was to test the hypothesis that dietary supplementation in early life will have an effect on rumen microbial composition that will persist even once supplementation is ceased. Twenty-seven new-born lambs were allocated to one of three dietary treatments; a control group receiving standard lamb meal, a group receiving lamb meal supplemented with 40 g kg-1 DM of linseed oil and a group receiving the supplement pre-weaning and standard lamb meal post-weaning. The supplement had no effect on average daily feed intake or average daily weight gain of lambs. Bacterial and archaeal community composition was significantly (p = 0.033 and 0.005, respectively) different in lambs fed linseed oil throughout the study compared to lambs on the control diet. Succinivibrionaceae, succinate producers, and Veillonellaceae, propionate producers, were in a higher relative abundance in the lambs fed linseed oil while Ruminococcaceae, a family linked with high CH4 emitters, were in a higher relative abundance in the control group. The relative abundance of Methanobrevibacter was reduced in the lambs receiving linseed compared to those that didn't. In contrast, the relative abundance of Methanosphaera was significantly higher in the animals receiving the supplement compared to animals receiving no supplement (40.82 and 26.67%, respectively). Furthermore, lambs fed linseed oil only in the pre-weaning period had a bacterial community composition significantly (p = 0.015) different to that of the control group, though archaeal diversity and community structure did not differ. Again, Succinivibrionaceae and Veillonellaceae were in a higher relative abundance in the group fed linseed oil pre-weaning while Ruminococcaceae were in a higher relative abundance in the control group. This study shows that lambs fed the dietary supplement short-term had a rumen microbiome that remained altered even after supplementation had ceased.

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Moderate recurrent hypoglycemia during early development leads to persistent changes in affective behavior in the rat.

Publications

Moderate recurrent hypoglycemia during early development leads to persistent changes in affective behavior in the rat.

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