Decreased Neuron Number and Synaptic Plasticity in SIRT3-Knockout Mice with Poor Remote Memory

Neurochem Res. 2019 Mar;44(3):676-682. doi: 10.1007/s11064-017-2417-3. Epub 2017 Oct 26.


The sirtuin family of proteins consists of nicotinamide adenine dinucleotide-dependent deacetylases that are involved in the response to calorie restriction and various physiological phenomena, such as aging and cognition. One of these proteins, sirtuin 3 (SIRT3), is localized in the mitochondria and protects the cell against oxidative or metabolic stress. Sirtuin protein deficiencies have been shown to accelerate neurodegeneration in neurotoxic conditions. The mechanisms underlying the involvement of SIRT3 in cognition remain unclear. Interestingly, SIRT1, another member of the sirtuin family, has been reported to modulate synaptic plasticity and memory formation. To learn more about these proteins, we examined the behavior and cognitive functions of Sirt3-knockout mice. The mice exhibited poor remote memory. Consistent with this, long-term potentiation was impaired in the Sirt3-knockout mice, and they exhibited decreased neuronal number in the anterior cingulate cortex, which seemed to contribute to their memory deficiencies.

Keywords: Neurodegeneration; Remote memory; Sirtuin; Synaptic plasticity.

MeSH terms

  • Animals
  • Long-Term Potentiation / genetics
  • Long-Term Potentiation / physiology*
  • Memory / physiology
  • Memory, Long-Term / physiology*
  • Mice, Knockout
  • Mitochondria / metabolism
  • Neuronal Plasticity / genetics
  • Neuronal Plasticity / physiology*
  • Neurons / metabolism*
  • Sirtuin 1 / genetics
  • Sirtuin 3 / deficiency*


  • Sirt3 protein, mouse
  • Sirtuin 1
  • Sirtuin 3