β2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis. (Nature medicine. 2015 doi:10.1038/nm.3898 (published online)

報告日期: 2015/12/04
報告時間: 4:00/4:50
報告學生: 蔡宗志
講評老師: 郭余民
附件下載: 下載[1533-1443056245-1.pdf] 

β2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis

Smith, L.K. et al. Nat. Med. 21, 932–937 (2015).

Speaker: 蔡宗志

Date:2015/12/04

Commentator:郭余民教授

Place: Room 602

    Aging makes cognitive function and neurogenesis decline in adult brain, especially in hippocampus. Previous studies showed that old mice could rejuvenate after injection with young mice blood plasma. Heterochronic parabiosis is a common aging animal model that two different age mice share the same circulatory systems. In this model, rejuvenation could be found in the multiple tissue in old mice such as heart, muscle, liver, pancreas, and brain. In 2011, Villeda found the levels of β2-microglobulin (B2M) were increased with age. B2M binds with MHC class I heavy chain to form MHC class I complex. In classical adaptive immunity, transporter associated with antigen processing (TAP) complex could promote MHC class I with antigen peptide to induce cytotoxic T cell immune response. Some studies have showed that high B2M concentration is correlated with cognitive dysfunction in the Alzheimer’s disease, HIV-associated dementia and chronic dialysis for kidney disease. However, the relationship between high elevated B2M with age and cognition function as well as neurogenesis is still unelucidated. In this study, the authors confirmed that B2M is elevated with age in circulating system and cerebral spinal fluid. Furthermore, administration B2M and heterochronic parabiosis both show the same impact on neurogenesis or hippocampal-dependent memory, but no effects were formed in Tap1-/- mice. In contrast, the loss of endogenous B2M could reverse poor cognitive performance and regenerative ability in old mice. In conclusion, the increased systemic B2M with age would decrease cognitive function and neurogenesis in adult brain through the MHC I complex.

References:

  1. Villeda, S.A. et al. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature 477, 90–94 (2011).
  2. Villeda, S.A. et al. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat. Med. 20, 659–663 (2014).