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Cited by 29Diabetes Management and ResearchStress Responses and CortisolPancreatic function and diabetes

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

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Moore, Holly, Craft, Tara K.S., Grimaldi, Lisa M., Babic, Bruna, Brunelli, Susan A., Vannucci, Susan J.·2010·Brain, Behavior, and Immunity
DOI 10.1016/j.bbi.2009.11.013PMC PMC2885529
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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.

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Authors
Moore, H., Craft, T. K. S., Grimaldi, L. M., Babic, B., Brunelli, S. A., & Vannucci, S. J.
Affiliations
  • Columbia University Irving Medical Center (US)
  • New York State Psychiatric Institute (US)
  • Morgan Stanley Children's Hospital (US)
Corresponding author
  • Moore, Holly
  • Vannucci, Susan J.
ORCID
Venue
Brain, Behavior, and Immunity
Publisher
Elsevier BV
Published
2010-07
Volume
24
Issue
5
Pages
839-849
ISSN
0889-1591 (ISSN-L)
DOI
10.1016/j.bbi.2009.11.013
PMC
PMC2885529
OpenAlex
W1975989979
Cited by
29
References
88
Citations by year
2024: 1 · 2022: 3 · 2020: 3 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 4 · 2015: 3 · 2014: 1 · 2013: 3 · 2012: 3
FWCI
1.46
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Behavior and Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Neurological Disorders and Stroke (R21NS045837, NS045837)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
recurrent hypoglycemia, insulin-induced hypoglycemia, emotional behavior, fear-potentiated startle, acoustic startle response, restraint stress, stress reactivity, social play, maternal separation, sex differences, developmental origins of behavior
MeSH terms
Analysis of Variance, Animals, Behavior, Animal, Blood Glucose, Female, Hypoglycemia, Insulin, Male, Maternal Deprivation, Motor Activity, Random Allocation, Recurrence, Restraint, Physical, Social Behavior, Stress, Physiological, Stress, Psychological, Rats, Sensory Gating

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