Upload
c-bouras
View
216
Download
0
Embed Size (px)
Citation preview
BioMed Central
Page 1 of 1(page number not for citation purposes)
Annals of General Hospital Psychiatry
Open AccessOral presentationImmunity and neuron: new evidence relating immunoglobulins to cytosceletal damageC Bouras*
Address: Professor, Head of service, Department of Psychiatry, Division of Neuropsychiatry, University Hospital of Geneva, Geneva Switzerland
* Corresponding author
Previous studies have suggested an increased activation ofhumoral immunity in neurodegenerative diseases, itremains unclear whether this phenomenon is secondaryto lesion formation or contributes directly to their devel-opment. Using stereotaxic injections in macaque monkeycerebral cortex, we studied the effects of human immu-noglobulins on the neuronal cytoskeleton. Under theseconditions, several MC-1-immunoreactive axons wereobserved in the vicinity of injection site. No MC-1 or TG-3 staining was detected in neuronal soma. Ultrastructur-ally, several axons in the same area displayed curly forma-tions and accumulation of twisted tubules but not pairedhelical filaments. These data suggest that Fc fragmentinduce conformational changes of tau and subtle struc-tural alterations in axons in this model. Immunocyto-chemical analyses in human autopsy materials revealedthe presence of human Fc fragments as well as Fc receptorsonly in large pyramidal neurons known to be vulnerablein brain aging and Alzheimer's disease, further supportinga possible role of immunoglobulins in neurodegenera-tion. Moreover, the influence of human immunoglobu-lins Ig in neuronal cytoskeleton stability was studied invitro. Here we show that human Ig and Fc fragments stim-ulate animal and human microtubule assembly by bind-ing to microtubules via tau isoforms. In presence of Igmicrotubules show increased aggregation twisting andrigidity. Non-immune Ig and Fc fragments promotemicrotubule assembly in temperature-dependent mannerand stabilize microtubules at a molecular ratio of Ig pertubulin dimers. These in vitro data provide an experimen-tal support for an immuno-mediated modulation of thecytoskeleton. These observations should be interpreted inconjunction with the consistent development of cytoskel-etal pathology in the aged human brain, raising the possi-
bility that nonspecific immune reactions may influencethe neuronal cytoskeleton and participate in structuralchanges in the early phases of neurodegeneration
from International Society on Brain and Behaviour: 1st International Congress on Brain and BehaviourHyatt Regency Hotel, Thessaloniki, Greece, 20–23 November, 2003
Published: 23 December 2003
Annals of General Hospital Psychiatry 2003, 2(Suppl 1):S19
Received: 1 November 2003<supplement> <title> <p>International Society on Brain and Behaviour: 1st International Congress on Brain and Behaviour</p> </title> <note>Meeting abstracts</note> </supplement>
This article is available from: http://www.general-hospital-psychiatry.com/content/2/S1/S19