Mice lacking interleukin-18 gene display behavioral changes in animal models of psychiatric disorders: Possible involvement of immunological mechanisms

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Mice lacking interleukin-18 gene display behavioral changes in animal models of psychiatric disorders : Possible involvement of immunological mechanisms. / Lisboa, S F; Issy, A C; Biojone, C; Montezuma, K; Fattori, V; Del-Bel, E A; Guimarães, F S; Cunha, F Q; Verri, W A; Joca, S R L.

In: Journal of Neuroimmunology, Vol. 314, 15.01.2018, p. 58-66.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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Lisboa, SF, Issy, AC, Biojone, C, Montezuma, K, Fattori, V, Del-Bel, EA, Guimarães, FS, Cunha, FQ, Verri, WA & Joca, SRL 2018, 'Mice lacking interleukin-18 gene display behavioral changes in animal models of psychiatric disorders: Possible involvement of immunological mechanisms', Journal of Neuroimmunology, vol. 314, pp. 58-66. https://doi.org/10.1016/j.jneuroim.2017.11.008

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CBE

Lisboa SF, Issy AC, Biojone C, Montezuma K, Fattori V, Del-Bel EA, Guimarães FS, Cunha FQ, Verri WA, Joca SRL. 2018. Mice lacking interleukin-18 gene display behavioral changes in animal models of psychiatric disorders: Possible involvement of immunological mechanisms. Journal of Neuroimmunology. 314:58-66. https://doi.org/10.1016/j.jneuroim.2017.11.008

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Lisboa, S F ; Issy, A C ; Biojone, C ; Montezuma, K ; Fattori, V ; Del-Bel, E A ; Guimarães, F S ; Cunha, F Q ; Verri, W A ; Joca, S R L. / Mice lacking interleukin-18 gene display behavioral changes in animal models of psychiatric disorders : Possible involvement of immunological mechanisms. In: Journal of Neuroimmunology. 2018 ; Vol. 314. pp. 58-66.

Bibtex

@article{da43b18507fb420bb7c2148b062996a6,
title = "Mice lacking interleukin-18 gene display behavioral changes in animal models of psychiatric disorders: Possible involvement of immunological mechanisms",
abstract = "Preclinical and clinical evidence suggests pro-inflammatory cytokines might play an important role in the neurobiology of schizophrenia and stress-related psychiatric disorders. Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines and it is widely expressed in brain regions involved in emotional regulation. Since IL-18 involvement in the neurobiology of mental illnesses, including schizophrenia, remains unknown, this work aimed at investigating the behavior of IL-18 null mice (KO) in different preclinical models: 1. the prepulse inhibition test (PPI), which provides an operational measure of sensorimotor gating and schizophrenic-like phenotypes; 2. amphetamine-induced hyperlocomotion, a model predictive of antipsychotic activity; 3. resident-intruder test, a model predictive of aggressive behavior. Furthermore, the animals were submitted to models used to assess depressive- and anxiety-like behavior. IL-18KO mice showed impaired baseline PPI response, which was attenuated by d-amphetamine at a dose that did not modify PPI response in wild-type (WT) mice, suggesting a hypodopaminergic prefrontal cortex function in those mice. d-Amphetamine, however, induced hyperlocomotion in IL-18KO mice compared to their WT counterparts, suggesting hyperdopaminergic activity in the midbrain. Moreover, IL-18KO mice presented increased basal levels of IL-1β levels in the hippocampus and TNF-α in the prefrontal cortex, suggesting an overcompensation of IL-18 absence by increased levels of other proinflammatory cytokines. Although no alteration was observed in the forced swimming or in the elevated plus maze tests in na{\"i}ve IL-18KO mice, these mice presented anxiogenic-like behavior after exposure to repeated forced swimming stress. In conclusion, deletion of the IL-18 gene resembled features similar to symptoms observed in schizophrenia (positive and cognitive symptoms, aggressive behavior), in addition to increased susceptibility to stress. The IL-18KO model, therefore, could provide new insights into how changes in brain immunological homeostasis induce behavioral changes related to psychiatric disorders, such as schizophrenia.",
keywords = "Journal Article",
author = "Lisboa, {S F} and Issy, {A C} and C Biojone and K Montezuma and V Fattori and Del-Bel, {E A} and Guimar{\~a}es, {F S} and Cunha, {F Q} and Verri, {W A} and Joca, {S R L}",
note = "Copyright {\circledC} 2017 Elsevier B.V. All rights reserved.",
year = "2018",
month = "1",
day = "15",
doi = "10.1016/j.jneuroim.2017.11.008",
language = "English",
volume = "314",
pages = "58--66",
journal = "Journal of Neuroimmunology",
issn = "0165-5728",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - Mice lacking interleukin-18 gene display behavioral changes in animal models of psychiatric disorders

T2 - Possible involvement of immunological mechanisms

AU - Lisboa, S F

AU - Issy, A C

AU - Biojone, C

AU - Montezuma, K

AU - Fattori, V

AU - Del-Bel, E A

AU - Guimarães, F S

AU - Cunha, F Q

AU - Verri, W A

AU - Joca, S R L

N1 - Copyright © 2017 Elsevier B.V. All rights reserved.

PY - 2018/1/15

Y1 - 2018/1/15

N2 - Preclinical and clinical evidence suggests pro-inflammatory cytokines might play an important role in the neurobiology of schizophrenia and stress-related psychiatric disorders. Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines and it is widely expressed in brain regions involved in emotional regulation. Since IL-18 involvement in the neurobiology of mental illnesses, including schizophrenia, remains unknown, this work aimed at investigating the behavior of IL-18 null mice (KO) in different preclinical models: 1. the prepulse inhibition test (PPI), which provides an operational measure of sensorimotor gating and schizophrenic-like phenotypes; 2. amphetamine-induced hyperlocomotion, a model predictive of antipsychotic activity; 3. resident-intruder test, a model predictive of aggressive behavior. Furthermore, the animals were submitted to models used to assess depressive- and anxiety-like behavior. IL-18KO mice showed impaired baseline PPI response, which was attenuated by d-amphetamine at a dose that did not modify PPI response in wild-type (WT) mice, suggesting a hypodopaminergic prefrontal cortex function in those mice. d-Amphetamine, however, induced hyperlocomotion in IL-18KO mice compared to their WT counterparts, suggesting hyperdopaminergic activity in the midbrain. Moreover, IL-18KO mice presented increased basal levels of IL-1β levels in the hippocampus and TNF-α in the prefrontal cortex, suggesting an overcompensation of IL-18 absence by increased levels of other proinflammatory cytokines. Although no alteration was observed in the forced swimming or in the elevated plus maze tests in naïve IL-18KO mice, these mice presented anxiogenic-like behavior after exposure to repeated forced swimming stress. In conclusion, deletion of the IL-18 gene resembled features similar to symptoms observed in schizophrenia (positive and cognitive symptoms, aggressive behavior), in addition to increased susceptibility to stress. The IL-18KO model, therefore, could provide new insights into how changes in brain immunological homeostasis induce behavioral changes related to psychiatric disorders, such as schizophrenia.

AB - Preclinical and clinical evidence suggests pro-inflammatory cytokines might play an important role in the neurobiology of schizophrenia and stress-related psychiatric disorders. Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines and it is widely expressed in brain regions involved in emotional regulation. Since IL-18 involvement in the neurobiology of mental illnesses, including schizophrenia, remains unknown, this work aimed at investigating the behavior of IL-18 null mice (KO) in different preclinical models: 1. the prepulse inhibition test (PPI), which provides an operational measure of sensorimotor gating and schizophrenic-like phenotypes; 2. amphetamine-induced hyperlocomotion, a model predictive of antipsychotic activity; 3. resident-intruder test, a model predictive of aggressive behavior. Furthermore, the animals were submitted to models used to assess depressive- and anxiety-like behavior. IL-18KO mice showed impaired baseline PPI response, which was attenuated by d-amphetamine at a dose that did not modify PPI response in wild-type (WT) mice, suggesting a hypodopaminergic prefrontal cortex function in those mice. d-Amphetamine, however, induced hyperlocomotion in IL-18KO mice compared to their WT counterparts, suggesting hyperdopaminergic activity in the midbrain. Moreover, IL-18KO mice presented increased basal levels of IL-1β levels in the hippocampus and TNF-α in the prefrontal cortex, suggesting an overcompensation of IL-18 absence by increased levels of other proinflammatory cytokines. Although no alteration was observed in the forced swimming or in the elevated plus maze tests in naïve IL-18KO mice, these mice presented anxiogenic-like behavior after exposure to repeated forced swimming stress. In conclusion, deletion of the IL-18 gene resembled features similar to symptoms observed in schizophrenia (positive and cognitive symptoms, aggressive behavior), in addition to increased susceptibility to stress. The IL-18KO model, therefore, could provide new insights into how changes in brain immunological homeostasis induce behavioral changes related to psychiatric disorders, such as schizophrenia.

KW - Journal Article

U2 - 10.1016/j.jneuroim.2017.11.008

DO - 10.1016/j.jneuroim.2017.11.008

M3 - Journal article

C2 - 29195684

VL - 314

SP - 58

EP - 66

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

SN - 0165-5728

ER -