Evidence for activation of microglia in patients with psychiatric illnesses

doi:10.1016/S0304-3940(99)00545-5

Neuroscience Letters

Volume 271, Issue 2, 20 August 1999, Pages 126-128

https://doi.org/10.1016/S0304-3940(99)00545-5 Get rights and content

Abstract

Activation of microglia/macrophages is a key event in response to pathological changes in the CNS. HLA-DR is a valuable immunohistochemical marker that specifically reacts with activated microglia cells. In order to elucidate a potential role of microgliosis in severe psychiatric illnesses, post-mortem frontal cortex and hippocampus of patients with schizophrenia (n=14) and affective disorder (n=6) and control specimens (n=13) were studied. Additionally Alzheimer's disease cases (n=8) were included as a human model system with typical neurodegenerative alterations and microglia activation. All patient groups revealed subjects with abundant microglia immunostaining (schizophrenia, three patients; affective disorder, one patient; Alzheimer's disease, four patients) in both gray and white matter. This finding provides evidence for distinct neuropathological changes in brains of patients with schizophrenia and affective disorder. The activation of microglia cells, which represent a major part of the brain immune response, may help to unravel the pathophysiological processes in severe psychiatric illnesses.

Section snippets

Acknowledgements

The Vada and Theodore Stanley Foundation have supported the present study. The technical support of Ulrich Klatt is gratefully acknowledged. We thank Professor Dr. O.D. Wiestler for generous supply of paraffin-embedded human brain material.

References (20)

G.W. Kreutzberg
Microglia: a sensor for pathological events in the CNS
Trends Neurosci.
(1996)
J.L. Ridet et al.
Reactive astrocytes: cellular and molecular cues to biological function
Trends Neurosci.
(1997)
G.W. Roberts et al.
Is there gliosis in schizophrenia? Investigation of the temporal lobe
Biol. Psychiatry
(1987)
G.W. Roberts et al.
Gliosis in schizophrenia: a survey
Biol. Psychiatry
(1986)
American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders. In A.P. Association (Eds.),...
S.E. Arnold et al.
Glial fibrillary acidic protein-immunoreactive astrocytosis in elderly patients with schizophrenia and dementia
Acta Neuropathol. (Berlin)
(1996)
S.E. Arnold et al.
Recent advances in defining the neuropathology of schizophrenia
Acta Neuropathol. (Berlin)
(1996)
S.E. Arnold et al.
Absence of neurodegeneration and neural injury in the cerebral cortex in a sample of elderly patients with schizophrenia
Arch. Gen. Psychiatry
(1998)
H. Braak et al.
Neuropathological staging of Alzheimer-related changes
Acta Neuropathol.
(1991)
E.Y. Chen et al.
Prefrontal neuropsychological impairment and illness duration in schizophrenia: a study of 204 patients in Hong Kong
Acta Psychiatr. Scand.
(1996)

There are more references available in the full text version of this article.

Cited by (288)

Maternal infection during pregnancy aggravates the behavioral response to an immune challenge during adolescence in female rats
2023, Behavioural Brain Research
Prenatal and early postnatal infection have been associated with changes in microglial activity and the development of psychiatric disorders. Here, we investigated the effect of prenatal immune activation and postnatal immune challenge, alone and combined, on behavior and microglial cell density in female Wistar rats. Pregnant rats were injected with poly I:C to induce a maternal immune activation (MIA). Their female offspring were subsequently exposed to a lipopolysaccharide (LPS) immune challenge during adolescence. Anhedonia, social behavior, anxiety, locomotion, and working memory were measured with the sucrose preference, social interaction, open field, elevated-plus maze, and Y-maze test, respectively. Microglia cell density was quantified by counting the number of Iba-1 positive cells in the brain cortex. Female MIA offspring were more susceptible to the LPS immune challenge during adolescence than control offspring as demonstrated by a more pronounced reduction in sucrose preference and body weight on the days following the LPS immune challenge. Furthermore, only the rats exposed to both MIA and LPS showed long-lasting changes in social behavior and locomotion. Conversely, the combination MIA and LPS prevented the anxiety induced by MIA alone during adulthood. MIA, LPS, or their combination did not change microglial cell density in the parietal and frontal cortex of adult rats. The results of our study suggest that the maternal immune activation during pregnancy aggravates the response to an immune challenge during adolescence in female rats.
Human stem cell-based models to study synaptic dysfunction and cognition in schizophrenia: A narrative review
2023, Schizophrenia Research
Cognitive impairment is the strongest predictor of functional outcomes in schizophrenia and is hypothesized to result from synaptic dysfunction. However, targeting synaptic plasticity and cognitive deficits in patients remains a significant clinical challenge. A comprehensive understanding of synaptic plasticity and the molecular basis of learning and memory in a disease context can provide specific targets for the development of novel therapeutics targeting cognitive impairments in schizophrenia. Here, we describe the role of synaptic plasticity in cognition, summarize evidence for synaptic dysfunction in schizophrenia and demonstrate the use of patient derived induced-pluripotent stem cells for studying synaptic plasticity in vitro. Lastly, we discuss current advances and future technologies for bridging basic science research of synaptic dysfunction with clinical and translational research that can be used to predict treatment response and develop novel therapeutics.
Beyond the neuron: Role of non-neuronal cells in stress disorders
2022, Neuron
Stress disorders are leading causes of disease burden in the U.S. and worldwide, yet available therapies are fully effective in less than half of all individuals with these disorders. Although to date, much of the focus has been on neuron-intrinsic mechanisms, emerging evidence suggests that chronic stress can affect a wide range of cell types in the brain and periphery, which are linked to maladaptive behavioral outcomes. Here, we synthesize emerging literature and discuss mechanisms of how non-neuronal cells in limbic regions of brain interface at synapses, the neurovascular unit, and other sites of intercellular communication to mediate the deleterious, or adaptive (i.e., pro-resilient), effects of chronic stress in rodent models and in human stress-related disorders. We believe that such an approach may one day allow us to adopt a holistic “whole body” approach to stress disorder research, which could lead to more precise diagnostic tests and personalized treatment strategies.
Brain targeting drug delivery systems for the management of brain disorders: molecular targets and nanotechnological strategies
2022, Multifunctional Nanocarriers
Brain disorders can be defined as injury or inflammation in neuronal circuits. Under the umbrella of brain disorders, Alzheimer's disease (AD), Parkinson's disease (PD), Multiple Sclerosis (MS), migraine, epilepsy, depression, motor nerve cell disorders, stroke, or Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, brain infection, and brain cancer are mostly covered. In brain disorders, the blood-brain barrier (BBB) defensive mechanism is harshly damaged. The scientific fraternity has discovered drugs of several categories for the management of brain disorders, however; owing to poor physicochemical attributes, drugs usually do not cross BBB to attain targeted drug delivery in the brain. Moreover, impaired transportation pathway of drugs during disease condition may change the both nonspecific and specific transport mechanisms. Recently, nanotechnology has provided many technical advances including invasive and noninvasive techniques directly targeting the brain with high efficiency and accuracy. Therefore, here, we have reviewed brain anatomy and physiology, routes of drug administration to brain, drug transport mechanisms, pathophysiology of brain disorders and their molecular targets, brain targeting drug delivery systems as well as management of brain disorders using nanotechnological approaches. Moreover, special attention has been emphasized on preclinical and clinical status of brain targeting drug delivery strategies.
T cell responses in depressed mice induced by chronic unpredictable mild stress
2022, Journal of Affective Disorders
The relationship between depression and adaptive immunity has gradually attracted increasing attentions. However, no consistent conclusions have been drawn about alterations in adaptive immunity in depression.
Eight-week-old weight-matched male C57BL/6 mice were randomly divided into a chronic unpredictable mild stress (CUMS) model group and a control group, with twelve mice in each group. After 8-week CUMS modeling duration and depressive behavioral tests, T cell responses were evaluated at the cell, cytokine, and cell-specific transcription factor levels. Lymphocytes in the spleen were detected by flow cytometry; serum cytokines were assessed by enzyme-linked immunosorbent assays; expression levels of cytokines and cell-specific transcription factors in the hippocampus were determined by quantitative PCR.
CUMS exposure induced depression-like behaviors with decreased sucrose preference and longer immobility time in the tail suspension test and forced swim test. The CUMS group had a lower proportion of CD4⁺ T cells than the control group. A decreased number of T helper 17 (Th17) cells in the spleen and down regulated serum interleukin (IL)-17 and hippocampal retinoid-related orphan receptor-γt levels were detected in the CUMS group. Depressed mice in the CUMS group showed increases in serum IL-1β and IL-6 and hippocampal IL-6 and IL-4 levels.
The study was based on a mouse model. Further studies are needed to determine whether the results are applicable to patients with depression.
CUMS exposure can induce depression-like behaviors and decrease Th17 cell counts.
SARS-CoV-2-associated cytokine storm during pregnancy as a possible risk factor for neuropsychiatric disorder development in post-pandemic infants
2021, Neuropharmacology
A strong association between perinatal viral infections and neurodevelopmental disorders has been established. Both the direct contact of the virus with the developing brain and the strong maternal immune response originated by viral infections can impair proper neurodevelopment. Coronavirus disease 2019 (COVID-19), caused by the highly-infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently responsible for a large global outbreak and is a major public health issue. While initial studies focused on the viral impact on the respiratory system, increasing evidence suggest that SARS-CoV-2 infects other organs and tissues including the mature brain. While studies continue to determine the neuropathology associated to COVID-19, the consequences of SARS-CoV-2 infection to the developing brain remain largely unexplored. The present review discusses evidence suggesting that SARS-CoV-2 infection may have persistent effects on the course of pregnancy and on brain development. Studies have shown that several proinflammatory mediators which are increased in the SARS-CoV-2-associated cytokine storm, are also modified in other viral infections known to increase the risk of neurodevelopmental disorders. In this sense, further studies should assess the genuine effects of SARS-CoV-2 infection during pregnancy and delivery along with an extended follow-up of the offspring, including neurocognitive, neuroimaging, and electrophysiological examination. It also remains to be determined whether and by which mechanisms SARS-CoV-2 intrauterine and early life infection could lead to an increased risk of developing neuropsychiatric disorders, such as autism (ASD) and schizophrenia (SZ), in the offspring.
This article is part of the special Issue on ‘Cross Talk between Periphery and the Brain’.

View all citing articles on Scopus

View full text

Evidence for activation of microglia in patients with psychiatric illnesses

Abstract

Section snippets

Acknowledgements

Trends Neurosci.

Trends Neurosci.

Biol. Psychiatry

Biol. Psychiatry

Glial fibrillary acidic protein-immunoreactive astrocytosis in elderly patients with schizophrenia and dementia

Acta Neuropathol. (Berlin)

Recent advances in defining the neuropathology of schizophrenia

Acta Neuropathol. (Berlin)

Absence of neurodegeneration and neural injury in the cerebral cortex in a sample of elderly patients with schizophrenia

Arch. Gen. Psychiatry

Neuropathological staging of Alzheimer-related changes

Acta Neuropathol.

Prefrontal neuropsychological impairment and illness duration in schizophrenia: a study of 204 patients in Hong Kong

Acta Psychiatr. Scand.