Neuronal overexpression of Glo1 or amygdalar microinjection of methylglyoxal is sufficient to regulate anxiety-like behavior in mice

K. M J McMurray, Xue-Liang Du, M. Brownlee, A. A. Palmer

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

GLO1 (Glyoxalase1) is a ubiquitous cellular enzyme that detoxifies methylglyoxal (MG), which is a byproduct of glycolysis. Previously, we showed that ubiquitous overexpression of Glo1 reduced concentrations of MG and increased anxiety-like behavior, whereas systemic injection of MG reduced anxiety-like behavior. We further showed that MG is a competitive partial agonist at GABA-A receptors. Based on those data we hypothesized that modulation of GABAergic signaling by MG underlies Glo1 and MG's effects on anxiety-like behavior.As previous studies used ubiquitous overexpression, we sought to determine whether neuronal Glo1 overexpression was sufficient to increase anxiety-like behavior. We generated ROSA26 knock-in mice with a floxed-stop codon upstream from human Glo1 (FLOXGlo1KI) and bred them with mice expressing CRE recombinase under the direction of the S. ynapsin 1 promoter (Syn-CRE) to limit overexpression of Glo1 specifically to neurons.Furthermore, since previous administration of MG had been systemic, we sought to determine if direct microinjection of MG into the basolateral amygdala (BLA) was sufficient to reduce anxiety-like behavior. Thus, we performed bilateral microinjections of saline, MG (12. μM or 24. μM), or the positive control midazolam (4. mM) directly into the BLA.FLOXGlo1KIxSyn-CRE mice showed significantly increased anxiety-like behavior compared to their FLOXGLO1xWT littermates. In addition, bilateral microinjection of MG and midazolam significantly decreased anxiety-like behavior compared to saline treated mice. These studies suggest that anatomically specific manipulations of Glo1 and MG are sufficient to induce changes in anxiety-like behavior.

Original languageEnglish (US)
Pages (from-to)119-123
Number of pages5
JournalBehavioural Brain Research
Volume301
DOIs
StatePublished - Mar 15 2016

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Pyruvaldehyde
Microinjections
Anxiety
Midazolam
GABA-A Receptor Agonists
Recombinases
Terminator Codon
Glycolysis

Keywords

  • Anxiety
  • GLO1
  • Glyoxalase 1
  • Methylglyoxal
  • MG

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Neuronal overexpression of Glo1 or amygdalar microinjection of methylglyoxal is sufficient to regulate anxiety-like behavior in mice. / McMurray, K. M J; Du, Xue-Liang; Brownlee, M.; Palmer, A. A.

In: Behavioural Brain Research, Vol. 301, 15.03.2016, p. 119-123.

Research output: Contribution to journalArticle

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