16/6-idiotype expressing antibodies induce brain inflammation and cognitive impairment in mice: the mosaic of central nervous system involvement in lupus

Shaye Kivity, Aviva Katzav, Maria Teresa Arango, Moran Landau-Rabi, Yaron Zafrir, Nancy Agmon-Levin, Miri Blank, Juan-Manuel Anaya, Edna Mozes, Joab Chapman, Yehuda Shoenfeld

Resultado de la investigación: Contribución a una revistaArtículo

17 Citas (Scopus)

Resumen

BACKGROUND: The 16/6-idiotype (16/6-Id) of the human anti-DNA antibody was found to induce experimental lupus in naïve mice, manifested by production of autoantibodies, leukopenia and elevated inflammatory markers, as well as kidney and brain involvement. We assessed behavior and brain pathology of naive mice injected intra-cerebra-ventricularly (ICV) with the 16/6-Id antibody.

METHODS: C3H female mice were injected ICV to the right hemisphere with the human 16/6-Id antibody or commercial human IgG antibodies (control). The mice were tested for depression by the forced swimming test (FST), locomotor and explorative activity by the staircase test, and cognitive functions were examined by the novel object recognition and Y-maze tests. Brain slices were stained for inflammatory processes.

RESULTS: 16/6-Id injected mice were cognitively impaired as shown by significant differences in the preference for a new object in the novel object recognition test compared to controls (P = 0.012). Similarly, the preference for spatial novelty in the Y-maze test was significantly higher in the control group compared to the 16/6-Id-injected mice (42% vs. 9%, respectively, P = 0.065). Depression-like behavior and locomotor activity were not significantly different between the16/6-Id-injected and the control mice. Immunohistochemistry analysis revealed an increase in astrocytes and microglial activation in the hippocampus and amygdala, in the 16/6-Id injected group compared to the control.

CONCLUSIONS: Passive transfer of 16/6-Id antibodies directly into mice brain resulted in cognitive impairments and histological evidence for brain inflammation. These findings shed additional light on the diverse mosaic pathophysiology of neuropsychiatric lupus.See related Commentary article: http://www.biomedcentral.com/1741-7015/11/91.

Idioma originalInglés estadounidense
Páginas (desde-hasta)90-98
Número de páginas9
PublicaciónBMC Medicine
Volumen11
N.º1
DOI
EstadoPublicada - abr 4 2013

Huella dactilar

Encephalitis
Central Nervous System
Antibodies
Brain
Cerebrum
Locomotion
Depression
Inbred C3H Mouse
Antinuclear Antibodies
Leukopenia
Cognitive Dysfunction
Amygdala
Astrocytes
Autoantibodies
Cognition
Hippocampus
Immunoglobulin G
Immunohistochemistry
Pathology
Kidney

Citar esto

Kivity, Shaye ; Katzav, Aviva ; Arango, Maria Teresa ; Landau-Rabi, Moran ; Zafrir, Yaron ; Agmon-Levin, Nancy ; Blank, Miri ; Anaya, Juan-Manuel ; Mozes, Edna ; Chapman, Joab ; Shoenfeld, Yehuda. / 16/6-idiotype expressing antibodies induce brain inflammation and cognitive impairment in mice : the mosaic of central nervous system involvement in lupus. En: BMC Medicine. 2013 ; Vol. 11, N.º 1. pp. 90-98.
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title = "16/6-idiotype expressing antibodies induce brain inflammation and cognitive impairment in mice: the mosaic of central nervous system involvement in lupus",
abstract = "BACKGROUND: The 16/6-idiotype (16/6-Id) of the human anti-DNA antibody was found to induce experimental lupus in na{\"i}ve mice, manifested by production of autoantibodies, leukopenia and elevated inflammatory markers, as well as kidney and brain involvement. We assessed behavior and brain pathology of naive mice injected intra-cerebra-ventricularly (ICV) with the 16/6-Id antibody.METHODS: C3H female mice were injected ICV to the right hemisphere with the human 16/6-Id antibody or commercial human IgG antibodies (control). The mice were tested for depression by the forced swimming test (FST), locomotor and explorative activity by the staircase test, and cognitive functions were examined by the novel object recognition and Y-maze tests. Brain slices were stained for inflammatory processes.RESULTS: 16/6-Id injected mice were cognitively impaired as shown by significant differences in the preference for a new object in the novel object recognition test compared to controls (P = 0.012). Similarly, the preference for spatial novelty in the Y-maze test was significantly higher in the control group compared to the 16/6-Id-injected mice (42{\%} vs. 9{\%}, respectively, P = 0.065). Depression-like behavior and locomotor activity were not significantly different between the16/6-Id-injected and the control mice. Immunohistochemistry analysis revealed an increase in astrocytes and microglial activation in the hippocampus and amygdala, in the 16/6-Id injected group compared to the control.CONCLUSIONS: Passive transfer of 16/6-Id antibodies directly into mice brain resulted in cognitive impairments and histological evidence for brain inflammation. These findings shed additional light on the diverse mosaic pathophysiology of neuropsychiatric lupus.See related Commentary article: http://www.biomedcentral.com/1741-7015/11/91.",
author = "Shaye Kivity and Aviva Katzav and Arango, {Maria Teresa} and Moran Landau-Rabi and Yaron Zafrir and Nancy Agmon-Levin and Miri Blank and Juan-Manuel Anaya and Edna Mozes and Joab Chapman and Yehuda Shoenfeld",
year = "2013",
month = "4",
day = "4",
doi = "10.1186/1741-7015-11-90",
language = "English (US)",
volume = "11",
pages = "90--98",
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Kivity, S, Katzav, A, Arango, MT, Landau-Rabi, M, Zafrir, Y, Agmon-Levin, N, Blank, M, Anaya, J-M, Mozes, E, Chapman, J & Shoenfeld, Y 2013, '16/6-idiotype expressing antibodies induce brain inflammation and cognitive impairment in mice: the mosaic of central nervous system involvement in lupus', BMC Medicine, vol. 11, n.º 1, pp. 90-98. https://doi.org/10.1186/1741-7015-11-90

16/6-idiotype expressing antibodies induce brain inflammation and cognitive impairment in mice : the mosaic of central nervous system involvement in lupus. / Kivity, Shaye; Katzav, Aviva; Arango, Maria Teresa; Landau-Rabi, Moran; Zafrir, Yaron; Agmon-Levin, Nancy; Blank, Miri; Anaya, Juan-Manuel; Mozes, Edna; Chapman, Joab; Shoenfeld, Yehuda.

En: BMC Medicine, Vol. 11, N.º 1, 04.04.2013, p. 90-98.

Resultado de la investigación: Contribución a una revistaArtículo

TY - JOUR

T1 - 16/6-idiotype expressing antibodies induce brain inflammation and cognitive impairment in mice

T2 - the mosaic of central nervous system involvement in lupus

AU - Kivity, Shaye

AU - Katzav, Aviva

AU - Arango, Maria Teresa

AU - Landau-Rabi, Moran

AU - Zafrir, Yaron

AU - Agmon-Levin, Nancy

AU - Blank, Miri

AU - Anaya, Juan-Manuel

AU - Mozes, Edna

AU - Chapman, Joab

AU - Shoenfeld, Yehuda

PY - 2013/4/4

Y1 - 2013/4/4

N2 - BACKGROUND: The 16/6-idiotype (16/6-Id) of the human anti-DNA antibody was found to induce experimental lupus in naïve mice, manifested by production of autoantibodies, leukopenia and elevated inflammatory markers, as well as kidney and brain involvement. We assessed behavior and brain pathology of naive mice injected intra-cerebra-ventricularly (ICV) with the 16/6-Id antibody.METHODS: C3H female mice were injected ICV to the right hemisphere with the human 16/6-Id antibody or commercial human IgG antibodies (control). The mice were tested for depression by the forced swimming test (FST), locomotor and explorative activity by the staircase test, and cognitive functions were examined by the novel object recognition and Y-maze tests. Brain slices were stained for inflammatory processes.RESULTS: 16/6-Id injected mice were cognitively impaired as shown by significant differences in the preference for a new object in the novel object recognition test compared to controls (P = 0.012). Similarly, the preference for spatial novelty in the Y-maze test was significantly higher in the control group compared to the 16/6-Id-injected mice (42% vs. 9%, respectively, P = 0.065). Depression-like behavior and locomotor activity were not significantly different between the16/6-Id-injected and the control mice. Immunohistochemistry analysis revealed an increase in astrocytes and microglial activation in the hippocampus and amygdala, in the 16/6-Id injected group compared to the control.CONCLUSIONS: Passive transfer of 16/6-Id antibodies directly into mice brain resulted in cognitive impairments and histological evidence for brain inflammation. These findings shed additional light on the diverse mosaic pathophysiology of neuropsychiatric lupus.See related Commentary article: http://www.biomedcentral.com/1741-7015/11/91.

AB - BACKGROUND: The 16/6-idiotype (16/6-Id) of the human anti-DNA antibody was found to induce experimental lupus in naïve mice, manifested by production of autoantibodies, leukopenia and elevated inflammatory markers, as well as kidney and brain involvement. We assessed behavior and brain pathology of naive mice injected intra-cerebra-ventricularly (ICV) with the 16/6-Id antibody.METHODS: C3H female mice were injected ICV to the right hemisphere with the human 16/6-Id antibody or commercial human IgG antibodies (control). The mice were tested for depression by the forced swimming test (FST), locomotor and explorative activity by the staircase test, and cognitive functions were examined by the novel object recognition and Y-maze tests. Brain slices were stained for inflammatory processes.RESULTS: 16/6-Id injected mice were cognitively impaired as shown by significant differences in the preference for a new object in the novel object recognition test compared to controls (P = 0.012). Similarly, the preference for spatial novelty in the Y-maze test was significantly higher in the control group compared to the 16/6-Id-injected mice (42% vs. 9%, respectively, P = 0.065). Depression-like behavior and locomotor activity were not significantly different between the16/6-Id-injected and the control mice. Immunohistochemistry analysis revealed an increase in astrocytes and microglial activation in the hippocampus and amygdala, in the 16/6-Id injected group compared to the control.CONCLUSIONS: Passive transfer of 16/6-Id antibodies directly into mice brain resulted in cognitive impairments and histological evidence for brain inflammation. These findings shed additional light on the diverse mosaic pathophysiology of neuropsychiatric lupus.See related Commentary article: http://www.biomedcentral.com/1741-7015/11/91.

U2 - 10.1186/1741-7015-11-90

DO - 10.1186/1741-7015-11-90

M3 - Article

C2 - 23556432

VL - 11

SP - 90

EP - 98

JO - BMC Medicine

JF - BMC Medicine

SN - 1741-7015

IS - 1

ER -