Glutaminase C overexpression in the brain induces learning deficits, synaptic dysfunctions, and neuroinflammation in mice

Yi Wang, Yuju Li, Runze Zhao, Beiqing Wu, Blaise Lanoha, Zenghan Tong, Justin Peer, Jianhui Liu, Huangui Xiong, Yunlong Huang, Jialin Zheng

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Glutaminolysis, a metabolic process that converts glutamine to glutamate, is particularly important for the central nervous system since glutamate is the major transmitter of excitatory synapses. Glutaminase is the mitochondrial enzyme that catalyzes the first step of glutaminolysis. Two genes encode at least four isoforms of glutaminase in humans. Gls1 gene encodes isoforms kidney-type glutaminase (KGA) and glutaminase C (GAC) through alternative splicing, whereas Gls2 gene encodes liver-type glutaminase isoforms. KGA and GAC have been associated with several neurological diseases. However, it remains unclear whether changes in their expressions can directly cause brain abnormalities. Using a transgenic approach, we generated mice that overexpressed GAC in the brain. The resulting transgenic mice had severe impairments in spatial and fear learning compared with littermate controls. The learning deficits were consistent with diminished hippocampal long-term potentiation in the hippocampal slices of the GAC transgenic mice. Furthermore, we found increases in astrocyte and microglia markers, inflammatory factors, and a decrease in synapse marker synaptophysin, suggesting neuroinflammation and synaptic changes in the GAC transgenic mouse brains. In conclusion, these findings provide the first evidence that GAC overexpression in the brain has deleterious effects on learning and synaptic integrity in vivo.

Original languageEnglish (US)
Pages (from-to)135-145
Number of pages11
JournalBrain, Behavior, and Immunity
StatePublished - Nov 2017


  • Excitotoxicity
  • Glutaminase
  • Inflammation
  • Learning and memory
  • Neurodegeneration
  • Synaptic transmission
  • Transgenic model

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


Dive into the research topics of 'Glutaminase C overexpression in the brain induces learning deficits, synaptic dysfunctions, and neuroinflammation in mice'. Together they form a unique fingerprint.

Cite this