Metformin impairs spatial memory and visual acuity in old male mice

Nopporn Thangthaeng, Margaret Rutledge, Jessica M. Wong, Philip H. Vann, Michael J. Forster, Nathalie Sumien

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Metformin is an oral anti-diabetic used as first-line therapy for type 2 diabetes. Because benefits of metformin extend beyond diabetes to other age-related pathology, and because its effect on gene expression profiles resembles that of caloric restriction, metformin has a potential as an anti-aging intervention and may soon be assessed as an intervention to extend healthspan. However, beneficial actions of metformin in the central nervous system have not been clearly established. The current study examined the effect of chronic oral metformin treatment on motor and cognitive function when initiated in young, middle-aged, or old male mice. C57BL/6 mice aged 4, 11, or 22 months were randomly assigned to either a metformin group (2 mg/ml in drinking water) or a control group. The mice were monitored weekly for body weight, as well as food and water intake and a battery of behavioral tests for motor, cognitive and visual function was initiated after the first month of treatment. Liver, hippocampus and cortex were collected at the end of the study to assess redox homeostasis. Overall, metformin supplementation in male mice failed to affect blood glucose, body weights and redox homeostasis at any age. It also had no beneficial effect on age-related declines in psychomotor, cognitive or sensory functions. However, metformin treatment had a deleterious effect on spatial memory and visual acuity, and reduced SOD activity in brain regions. These data confirm that metformin treatment may be associated with deleterious effect resulting from the action of metformin on the central nervous system.

Original languageEnglish
Pages (from-to)17-30
Number of pages14
JournalAging and Disease
Volume8
Issue number1
DOIs
StatePublished - 1 Jan 2017

Fingerprint

Metformin
Visual Acuity
Cognition
Oxidation-Reduction
Homeostasis
Central Nervous System
Body Weight
Spatial Memory
Therapeutics
Caloric Restriction
Inbred C57BL Mouse
Transcriptome
Drinking Water
Type 2 Diabetes Mellitus
Drinking
Blood Glucose
Hippocampus
Eating
Pathology
Control Groups

Keywords

  • Aging
  • Antidiabetic
  • Antioxidant enzymes
  • Cognition
  • Metformin
  • Redox stress
  • Visual function

Cite this

Thangthaeng, Nopporn ; Rutledge, Margaret ; Wong, Jessica M. ; Vann, Philip H. ; Forster, Michael J. ; Sumien, Nathalie. / Metformin impairs spatial memory and visual acuity in old male mice. In: Aging and Disease. 2017 ; Vol. 8, No. 1. pp. 17-30.
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Metformin impairs spatial memory and visual acuity in old male mice. / Thangthaeng, Nopporn; Rutledge, Margaret; Wong, Jessica M.; Vann, Philip H.; Forster, Michael J.; Sumien, Nathalie.

In: Aging and Disease, Vol. 8, No. 1, 01.01.2017, p. 17-30.

Research output: Contribution to journalArticle

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