Taurine and N-acetylcysteine treatments prevent memory impairment and metabolite profile alterations in the hippocampus of high-fat diet-fed female mice

Nutr Neurosci. 2023 Nov;26(11):1090-1102. doi: 10.1080/1028415X.2022.2131062. Epub 2022 Oct 12.

Abstract

Background: Obesity constitutes a risk factor for cognitive impairment. In rodent models, long-term exposure to obesogenic diets leads to hippocampal taurine accumulation. Since taurine has putative cyto-protective effects, hippocampal taurine accumulation in obese and diabetic models might constitute a counteracting response to metabolic stress. Objective: We tested the hypothesis that treatment with taurine or with N-acetylcysteine (NAC), which provides cysteine for the synthesis of taurine and glutathione, prevent high-fat diet (HFD)-associated hippocampal alterations and memory impairment. Methods: Female mice were fed either a regular diet or HFD. Some mice had access to 3%(w/v) taurine or 3%(w/v) NAC in the drinking water. After 2 months, magnetic resonance spectroscopy (MRS) was used to measure metabolite profiles. Memory was assessed in novel object and novel location recognition tests. Results: HFD feeding caused memory impairment in both tests, and reduced concentration of lactate, phosphocreatine-to-creatine ratio, and the neuronal marker N-acetylaspartate in the hippocampus. Taurine and NAC prevented HFD-induced memory impairment and N-acetylaspartate reduction. NAC, but not taurine, prevented the reduction of lactate and phosphocreatine-to-creatine ratio. MRS revealed NAC/taurine-induced increase of hippocampal glutamate and GABA levels. Conclusion: NAC and taurine can prevent memory impairment, while only NAC prevents alterations of metabolite concentrations in HFD-exposed female mice.

Keywords: MRS; N-acetylaspartate; Obesity; diabetes; lactate; metabolism; neurochemical profile; neuroprotection.

MeSH terms

  • Acetylcysteine* / pharmacology
  • Acetylcysteine* / therapeutic use
  • Animals
  • Creatine / metabolism
  • Diet, High-Fat* / adverse effects
  • Female
  • Hippocampus / metabolism
  • Lactates / metabolism
  • Memory Disorders / etiology
  • Memory Disorders / prevention & control
  • Mice
  • Mice, Inbred C57BL
  • Obesity / metabolism
  • Phosphocreatine / metabolism

Substances

  • Acetylcysteine
  • Creatine
  • Phosphocreatine
  • Lactates