Sirtuin 1 overexpression mice show a reference memory deficit, but not neuroprotection

Biochem Biophys Res Commun. 2009 Oct 2;387(4):784-8. doi: 10.1016/j.bbrc.2009.07.119. Epub 2009 Jul 28.


Sirtuin 1 (SIRT1) is the closest mammalian homologue of yeast silent information regulator 2 (Sir2) and has a role in lifespan modulation. Reportedly, SIRT1 is also linked to neurodegenerative diseases. However, there are limited studies that report the relation between SIRT1 and neurodegenerative diseases using in vivo transgenic (Tg) methods. In the present study, we generated neuron-specific enolase (NSE) SIRT1 Tg mice that overexpress human SIRT1 in neurons. We examined possible neuroprotective effects of SIRT1 overexpression and compared their higher brain functions with those of wild-type (WT) mice. Overexpression of SIRT1 did not have any neuroprotective effects against the neuronal damage induced by ischemia or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, SIRT1 Tg mice exhibited a reference memory deficit. These findings suggest that an excessive expression of SIRT1 might induce the memory deficit in mice, but not neuroprotective effects.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
  • Animals
  • Brain Ischemia / complications
  • Memory Disorders / genetics*
  • Memory Disorders / physiopathology
  • Mice
  • Mice, Transgenic
  • Neurodegenerative Diseases / chemically induced
  • Neurodegenerative Diseases / etiology
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / physiopathology*
  • Neurons / enzymology*
  • Neurons / physiology
  • Neurotoxins / toxicity
  • Sirtuin 1
  • Sirtuins / genetics*
  • Sirtuins / metabolism


  • Neurotoxins
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • SIRT1 protein, human
  • Sirtuin 1
  • Sirtuins