LPS-dependent suppression of social exploration is augmented in type 1 diabetic mice

Keng I. Lin, Daniel R. Johnson, Gregory G. Freund

Research output: Contribution to journalArticlepeer-review


We have previously shown that type 2 diabetes (T2D) in the mouse is associated with increased responsivity to innate immune challenge. Here we demonstrate that in a mouse model of type 1 diabetes (T1D) LPS-dependent suppression of social exploration (SE) is augmented and dependent on hyperglycemia. T1D was induced in mice with intraperitoneal (i.p.) streptozotocin (STZ). After 4 d, STZ treated mice had blood glucose levels of 417 ± 34 mg/dl compared to 160 ± 11 mg/dl in non-STZ treated mice. When these diabetic mice were challenged with i.p. lipopolysaccharide (LPS), LPS-induced depression of SE was nearly 2.7-fold greater in diabetic mice at 2 h than in non-diabetic mice. Examination of peritoneal proinflammatory cytokine levels 2 h after LPS administration showed that diabetic mice had 4-, 2.5- and 3.6-fold greater concentrations of IL-1β, IL-6 and TNF-α, respectively, when compared to non-diabetic mice. Control of blood glucose levels with injected insulin in diabetic mice improved 2 h post LPS-induced loss of SE by 3.9-fold. Interestingly, insulin given intracerebroventricularly to diabetic mice did not impact LPS-induced loss of SE but did increase basal SE 8, 12 and 24 h later. Finally, administration of STZ to hyperglycemic/hyperinsulinemic db/db mice did not alter LPS-induced loss of SE. Taken together these findings indicate that mice with T1D have augmented loss of SE in response to LPS and this is due to hyperglycemia and not to insulin.

Original languageEnglish (US)
Pages (from-to)775-782
Number of pages8
JournalBrain, Behavior, and Immunity
Issue number6
StatePublished - Aug 2007


  • Cytokines
  • Lipopolysaccharide
  • Neuroimmunity
  • Sickness behavior
  • Social exploration
  • Social withdrawal
  • Type 1 diabetes

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


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