Neuropsychiatric Aspects of Cytokines Research: An Overview

Malek-Ahmadi, Parviz

doi:10.1016/0149-7634(95)00056-9

Cited by 26 publications

(10 citation statements)

References 76 publications

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“…In particular, altered expression of cytokines may play a role in the pathogenesis of neuropsychiatric diseases in childhood (Malek-Ahmadi, 1996). Although some studies have shown no difference in CSF cytokine profiles in schizophrenia (Baker et al, 1996;el-Mallakh et al, 1993), others have reported elevations of IL-1␤ or IL-2 in adult schizophrenics (Katila et al, 1994;McAllister et al, 1995).…”

Section: Behavior and Psychiatric Disordersmentioning

confidence: 97%

“…Systemic use of cytokines can cause neuropsychiatric side effects in psychiatrically healthy individuals (Hickie and Lloyd, 1995;Malek-Ahmadi, 1996;Triozzi et al, 1990). However, certain cytokines have been successfully used as therapeutic agents in neurologic disorders, while some psychotropic agents are capable of altering the production and release of cytokines (Gallicchio et al, 1984;Whicher and Evans, 1990).…”

Section: Roles Of Cytokines In Brain Injury and Neurodegenerationmentioning

confidence: 98%

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Involvement of cytokines in normal CNS development and neurological diseases: Recent progress and perspectives

1998

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Cytokines have been recognized to play an important role both in normal development of the brain, when they act as neurotrophic factors, as well as following injury. While both the cytokines and their receptors are synthesized and expressed in the brain normally (albeit at low levels), it has become clear that elevated levels are associated with many neurological disorders. In this review, we have chosen to present the data for only a few of the cytokines, including interleukin-1beta, interleukin-3, interleukin-6, interferon-gamma, transforming growth factor-beta, and tumor necrosis factor-alpha. Data are presented that suggest roles they may play in human disorders, including stroke, multiple sclerosis, Alzheimer's disease, and several psychiatric disorders. The results in human disease are compared with results obtained in a variety of transgenic animal models. The mouse models have very different disorders depending on whether a cytokine is overexpressed either peripherally or in either astrocytes or neurons. The potential significance of this to the understanding of human disease is discussed.

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Section: Behavior and Psychiatric Disordersmentioning

confidence: 97%

Section: Roles Of Cytokines In Brain Injury and Neurodegenerationmentioning

confidence: 98%

Involvement of cytokines in normal CNS development and neurological diseases: Recent progress and perspectives

1998

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“…As GDs 15-17 is a time when the entorhinal cortex, and the CA1 and CA3 fields undergo neurogenesis Bayer et al, , 1993, it is likely that poly I : C-induced maternal immune activation interfered with the normal development of these fetal sites. The precise mechanisms by which maternal immune response may affect the developing brain remain to be elucidated, but maternally generated cytokines are believed to be involved, because of the following reasons: (1) they can enter the fetal circulation and influence cytokine levels in the fetal brain; and (2) there is evidence from in vitro and in vivo studies that cytokines regulate brain development (Malek-Ahmadi, 1996;Marx et al, 2001;Medlock et al, 1993;Mehler and Kessler, 1998;Merrill, 1992;Patterson and Nawa, 1993;Rothwell and Hopkins, 1995;Urakubo et al, 2001). Particularly relevant in the present context are the findings that cytokines detrimentally affect the developing hippocampal neurons (Araujo and Cotman, 1995;Jarskog et al, 1997).…”

Section: Prenatal Immune Activation and Latent Inhibitionmentioning

confidence: 99%

Immune Activation During Pregnancy in Rats Leads to a PostPubertal Emergence of Disrupted Latent Inhibition, Dopaminergic Hyperfunction, and Altered Limbic Morphology in the Offspring: A Novel Neurodevelopmental Model of Schizophrenia

Zuckerman

Rehavi

Nachman

et al. 2003

Neuropsychopharmacol

442

355

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Prenatal exposure to infection is associated with increased liability to schizophrenia, and it is believed that such an association is mediated by the maternal immune response, in particular, the proinflammatory cytokines released by the maternal immune system, which may disrupt fetal brain development. Impaired capacity to ignore irrelevant stimuli is one of the central deficits in schizophrenia, and is manifested, among others, in loss of latent inhibition (LI), a phenomenon whereby repeated inconsequential pre-exposure to a stimulus impairs its subsequent capacity to signal significant consequences. We tested the effects of prenatal immune activation induced by peripheral administration of the synthetic cytokine releaser polyriboinosinic-polyribocytidilic acid (poly I : C) to pregnant dams, on LI in juvenile and adult offspring. Consistent with the characteristic maturational delay of schizophrenia, prenatal immune activation did not affect LI in the juvenile offspring, but led to LI disruption in adulthood. Both haloperidol (0.1 mg/kg) and clozapine (5 mg/kg) reinstated LI in the adult offspring. In addition, prenatal immune activation led to a postpubertal emergence of increased sensitivity to the locomotorstimulating effects of amphetamine and increased in vitro striatal dopamine release, as well as to morphological alterations in the hippocampus and the entorhinal cortex in the adult offspring, consistent with the well-documented mesolimbic dopaminergic and temporolimbic pathology in schizophrenia. These results suggest that prenatal poly I : C administration may provide a neurodevelopmental model of schizophrenia that reproduces a putative inducing factor; mimics the temporal course as well as some central abnormalities of the disorder; and predicts responsiveness to antipsychotic drugs.

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“…95 Conversely, impaired production and abnormal content of various cytokines are detected in schizophrenic patients (further information can be found in several reviews). 12,14,75,94 These and other studies highlight the potential influence of environmental events, such as peripheral infection, on brain function, with particular focus on brain cytokines. 12,14,90,96 Interaction between cytokines and neuronal differentiation factors in the brain As cited above, epidemiological studies have indicated that environmental factors such as the season of birth and prenatal viral infection are significant risk factors for schizophrenia.…”

Section: Neuronal Differentiation and Trophic Factors In Schizophreniamentioning

confidence: 99%

“…12 Indeed, there is a bi-directional communication between the brain and the immune system, such that alterations in one can lead to profound changes in the other, during development as well as in maturity. 13,14 In this review, we first summarize relevant pathological and molecular findings for schizophrenia and correlate them with abnormalities found in the neurotrophic factor/cytokine systems thus far. We draw attention to the roles of growth factors and cytokines in regulating brain development, and particularly the control of those proteins that are known to be altered in schizophrenia.…”

Section: Nutritionalmentioning

confidence: 99%

Cytokine and growth factor involvement in schizophrenia—support for the developmental model

2000

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Medical treatment with various cytokines can provoke psychiatric symptoms. Conversely, psychiatric patients can display abnormalities in cytokine and neurotrophic factor expression. Such observations have pointed to the potential contribution of cytokines and growth factors to schizophrenic pathology and/or etiology. The cellular targets of the relevant factors and the nature of their actions remain to be explored in mental illness, however. Recent physiological studies demonstrate that cytokines and neurotrophic factors can markedly influence synaptic transmission and plasticity upon acute or chronic application. Moreover, many of the molecular alterations observed in the schizophrenic brain are consistent with abnormalities in cytokine and neurotrophic factor regulation of these molecules. In this review, we summarize these molecular pathology findings for schizophrenia and highlight the neurodevelopmental activities of cytokines and neurotrophic factors that may contribute to the etiology or pathology of this illness. Molecular Psychiatry (2000) 5, 594-603.

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Neuropsychiatric Aspects of Cytokines Research: An Overview

Cited by 26 publications

References 76 publications

Involvement of cytokines in normal CNS development and neurological diseases: Recent progress and perspectives

Involvement of cytokines in normal CNS development and neurological diseases: Recent progress and perspectives

Immune Activation During Pregnancy in Rats Leads to a PostPubertal Emergence of Disrupted Latent Inhibition, Dopaminergic Hyperfunction, and Altered Limbic Morphology in the Offspring: A Novel Neurodevelopmental Model of Schizophrenia

Cytokine and growth factor involvement in schizophrenia—support for the developmental model

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