Higher GABA concentration in the medial prefrontal cortex of Type 2 diabetes patients is associated with episodic memory dysfunction

Jan Willem Thielen*, Sofiya Gancheva, Donghyun Hong, Seyedmorteza Rohani Rankouhi, Bixia Chen, Maria Apostolopoulou, Evrim Anadol-Schmitz, Michael Roden, David G. Norris, Indira Tendolkar

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

Type 2 diabetes (T2D) is associated with an accelerated episodic memory decline, but the underlying pathophysiological mechanisms are not well understood. Hallmarks of T2D comprise impairment of insulin secretion and insulin sensitivity. Insulin signaling modulates cerebral neurotransmitter activity, including the excitatory glutamate and inhibitory gamma-aminobutyric acid (GABA) systems. Here we tested the hypothesis that the glutamate and GABA systems are altered in T2D patients and this relates to memory decline and insulin resistance. Using 1H-magnetic resonance spectroscopy (MRS), we examined glutamate and GABA concentrations in episodic memory relevant brain regions (medial prefrontal cortex and precuneus) of T2D patients and matched controls. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamps and memory performance was assessed using a face-profession associations test. T2D patients exhibited peripheral insulin resistance and had a decreased memory for face-profession associations as well as elevated GABA concentration in the medial prefrontal cortex but not precuneus. In addition, medial prefrontal cortex GABA concentration was negatively associated with memory performance suggesting that abnormal GABA levels in the medial prefrontal cortex are linked to the episodic memory decline that occurs in T2D patients.

Original languageEnglish
Pages (from-to)4287-4295
Number of pages9
JournalHuman brain mapping
Volume40
Issue number14
Early online date2 Jul 2019
DOIs
Publication statusPublished - 1 Oct 2019

Keywords

  • diabetes
  • magnetic resonance spectroscopy
  • Memory

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    Thielen, J. W., Gancheva, S., Hong, D., Rohani Rankouhi, S., Chen, B., Apostolopoulou, M., ... Tendolkar, I. (2019). Higher GABA concentration in the medial prefrontal cortex of Type 2 diabetes patients is associated with episodic memory dysfunction. Human brain mapping, 40(14), 4287-4295. https://doi.org/10.1002/hbm.24702