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BioMed Central Page 1 of 1 (page number not for citation purposes) Annals of General Hospital Psychiatry Open Access Oral presentation Immunity and neuron: new evidence relating immunoglobulins to cytosceletal damage C 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 of humoral immunity in neurodegenerative diseases, it remains unclear whether this phenomenon is secondary to lesion formation or contributes directly to their devel- opment. Using stereotaxic injections in macaque monkey cerebral cortex, we studied the effects of human immu- noglobulins on the neuronal cytoskeleton. Under these conditions, several MC-1-immunoreactive axons were observed 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 paired helical filaments. These data suggest that Fc fragment induce conformational changes of tau and subtle struc- tural alterations in axons in this model. Immunocyto- chemical analyses in human autopsy materials revealed the presence of human Fc fragments as well as Fc receptors only in large pyramidal neurons known to be vulnerable in brain aging and Alzheimer's disease, further supporting a possible role of immunoglobulins in neurodegenera- tion. Moreover, the influence of human immunoglobu- lins Ig in neuronal cytoskeleton stability was studied in vitro. 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 Ig microtubules show increased aggregation twisting and rigidity. Non-immune Ig and Fc fragments promote microtubule assembly in temperature-dependent manner and stabilize microtubules at a molecular ratio of Ig per tubulin dimers. These in vitro data provide an experimen- tal support for an immuno-mediated modulation of the cytoskeleton. These observations should be interpreted in conjunction with the consistent development of cytoskel- etal pathology in the aged human brain, raising the possi- bility that nonspecific immune reactions may influence the neuronal cytoskeleton and participate in structural changes in the early phases of neurodegeneration from International Society on Brain and Behaviour: 1st International Congress on Brain and Behaviour Hyatt 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

Immunity and neuron: new evidence relating immunoglobulins to cytosceletal damage

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Page 1: Immunity and neuron: new evidence relating immunoglobulins to cytosceletal damage

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