Beta N-acetylglucosaminyltransferase V (Mgat5) deficiency reduces the depression-like phenotype in mice

Genes Brain Behav. 2008 Apr;7(3):334-43. doi: 10.1111/j.1601-183X.2007.00358.x. Epub 2007 Sep 18.

Abstract

The central nervous system (CNS) is rich in glycoconjugates, located on cell surface and in extracellular matrix. The products of Golgi UDP-GlcNAc:N-acetylglucosaminyltransferases (encoded by Mgat1, Mgat2, Mgat4 and Mgat5) act sequentially to generate the GlcNAc-branched complex-type N-glycans on glycoprotein receptors. While elimination of all the branched N-glycans in Mgat1(-/-) mouse embryos is lethal at neural tube fold stage, decreased branching is associated with late developmental defects similar to type 2 of congenital disorders of glycosylation, with developmental and psychomotor abnormalities. To study the role of complex-type N-glycans in brain function, we tested Mgat5(-/-) mice in a battery of neurological and behavioral tests. Despite the absence of tri- and tetra-antennary products, Mgat5(-/-) mice were not different from their wild-type littermates in physical and neurological assessments, anxiety level, startle reactivity and sensorimotor gating. However, they displayed a robust decrease in the immobility time in the forced swim test and the tail suspension test independent of locomotor activity, interpreted as a change in depression-like behavior. This effect was accentuated after chronic mild stress. Comparable increase in plasma corticosterone of Mgat5(+/+) and Mgat5(-/-) mice in response to acute stress shows an intact function of the hypothalamus-pituitary-adrenal axis. A change in social interactions was also observed. Our results indicate that Mgat5 modification of complex-type N-glycans on CNS glycoproteins is involved in the regulation of depression-like behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Behavior, Animal
  • Depression / enzymology
  • Depression / genetics*
  • Depression / prevention & control*
  • Emotions
  • Glycoproteins / metabolism
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity / drug effects
  • N-Acetylglucosaminyltransferases / deficiency*
  • Polysaccharides / metabolism
  • Reaction Time
  • Stress, Psychological / genetics
  • Swimming

Substances

  • Antidepressive Agents
  • Glycoproteins
  • Polysaccharides
  • N-Acetylglucosaminyltransferases
  • alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase