Cognition and Immunity

  • Kowal C
  • DeGiorgio L
  • Nakaoka T
  • et al.
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Patients with lupus (SLE) experience progressive cog- nitive loss without evidence of CNS vascular disease or inflammation. SLE patients produce anti-DNA anti- bodies that crossreact with NMDA receptors and are capable of mediating excitotoxic death. We now show that mice induced by antigen to express these anti- bodies have no neuronal damage until breakdown of the blood-brain barrier occurs. Following administra- tion of lipopolysaccharide (LPS) to immunized mice, antibodies gain access to the brain. They bind pref- erentially to hippocampal neurons and cause neuronal death with resulting cognitive dysfunction and altered hippocampalmetabolismon magnetic resonance spec- troscopy. Memantine, an NMDA receptor antagonist, given prior to LPS administration, prevents neuronal damage.Thus, systemicimmuneresponses cancause cognitive impairment in the absence of an inflamma- tory cascade, implicating the immune system in yet another arena of human pathobiology. Furthermore, NMDA receptor antagonists prevent antibody-medi- ated damage and may constitute a new approach to therapy in SLE.




Kowal, C., DeGiorgio, L. A., Nakaoka, T., Hetherington, H., Huerta, P. T., Diamond, B., & Volpe, B. T. (2004). Cognition and Immunity. Immunity, 21(2), 179–188.

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