Schizophrenia associated sensory gating deficits develop after adolescent microglia activation

Eßlinger, Manuela; Wachholz, Simone; Manitz, Marie-Pierre; Plümper, Jennifer; Sommer, Rainer; Juckel, Georg; Friebe, Astrid

doi:10.1016/j.bbi.2016.05.018

Cited by 37 publications

(41 citation statements)

References 48 publications

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“…More recently combining MRI and genome-wide transcription or proteomics analysis suggests MIA induces myelin dysfunction, which will be important to explore in terms of our observations of increased white matter volume (Farrelly et al, 2015, Richetto et al, 2016). There is also evidence for decreased levels of in synaptic proteins in the hippocampus and PFC of POL-exposed mice (Giovanoli et al, 2015, Giovanoli et al, 2016), whilst evidence for microglial activation is equivocal (Giovanoli et al, 2015, Giovanoli et al, 2016; Mattei et al, 2014, Eßlinger et al, 2016). Further work to link neuroimaging and neuropathology in this model is therefore required.…”

Section: Discussionmentioning

confidence: 99%

Evolution of structural abnormalities in the rat brain following in utero exposure to maternal immune activation: A longitudinal in vivo MRI study

Crum

Sawiak

Chege

et al. 2017

Brain, Behavior, and Immunity

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Section: Discussionmentioning

confidence: 99%

Evolution of structural abnormalities in the rat brain following in utero exposure to maternal immune activation: A longitudinal in vivo MRI study

Crum

Sawiak

Chege

et al. 2017

Brain, Behavior, and Immunity

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“…Studies on animals infected by pathogenic bacteria, or treated with probiotic or antibiotic agents have suggested that gut microbiota may play a role in the genesis of multiple sclerosis, anxiety and depression (Berer et al, 2011; Cryan and Dinan, 2012). However, many psychiatric co-morbidities are thought to be the result of perinatal infections, and should be interpreted within the context of altered predisposition rather than microbiota-CNS communication (Buka et al, 2008; Eßlinger et al, 2016; Gilman et al, 2016). Since clear evidence of the role of gut microbiota in the development of these syndromes is still lacking, this subject is still the topic of debate.…”

Section: Microbial Neuro-immuno-endocrinology: How Gut Microbiota Andmentioning

confidence: 99%

The Neuro-endocrinological Role of Microbial Glutamate and GABA Signaling

2016

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Gut microbiota provides the host with multiple functions (e.g., by contributing to food digestion, vitamin supplementation, and defense against pathogenic strains) and interacts with the host organism through both direct contact (e.g., through surface antigens) and soluble molecules, which are produced by the microbial metabolism. The existence of the so-called gut–brain axis of bi-directional communication between the gastrointestinal tract and the central nervous system (CNS) also supports a communication pathway between the gut microbiota and neural circuits of the host, including the CNS. An increasing body of evidence has shown that gut microbiota is able to modulate gut and brain functions, including the mood, cognitive functions, and behavior of humans. Nonetheless, given the extreme complexity of this communication network, its comprehension is still at its early stage. The present contribution will attempt to provide a state-of-the art description of the mechanisms by which gut microbiota can affect the gut–brain axis and the multiple cellular and molecular communication circuits (i.e., neural, immune, and humoral). In this context, special attention will be paid to the microbial strains that produce bioactive compounds and display ascertained or potential probiotic activity. Several neuroactive molecules (e.g., catecholamines, histamine, serotonin, and trace amines) will be considered, with special focus on Glu and GABA circuits, receptors, and signaling. From the basic science viewpoint, “microbial endocrinology” deals with those theories in which neurochemicals, produced by both multicellular organisms and prokaryotes (e.g., serotonin, GABA, glutamate), are considered as a common shared language that enables interkingdom communication. With regards to its application, research in this area opens the way toward the possibility of the future use of neuroactive molecule-producing probiotics as therapeutic agents for the treatment of neurogastroenteric and/or psychiatric disorders.

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“…18 Recently, prenatal immune activation was shown to be associated with a shift towards the M1 pathway in adolescence, and subsequent adult sensory gating deficits. 19 …”

Section: The Immune System and Gliamentioning

confidence: 99%

“…26, 147 Second, it appears that pathological overactivation of microglia occurs early in the course of the illness. 19, 57, 65 Thus treatment may need to be given early, potentially during a prodromal period, to be effective and to prevent the secondary loss of synapses.…”

Section: Implications For Treatmentmentioning

confidence: 99%

Inflammation and the neural diathesis-stress hypothesis of schizophrenia: a reconceptualization

2017

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An interaction between external stressors and intrinsic vulnerability is one of the longest standing pathoaetiological explanations for schizophrenia. However, novel lines of evidence from genetics, preclinical studies, epidemiology and imaging have shed new light on the mechanisms that may underlie this, implicating microglia as a key potential mediator. Microglia are the primary immune cells of the central nervous system. They have a central role in the inflammatory response, and are also involved in synaptic pruning and neuronal remodeling. In addition to immune and traumatic stimuli, microglial activation occurs in response to psychosocial stress. Activation of microglia perinatally may make them vulnerable to subsequent overactivation by stressors experienced in later life. Recent advances in genetics have shown that variations in the complement system are associated with schizophrenia, and this system has been shown to regulate microglial synaptic pruning. This suggests a mechanism via which genetic and environmental influences may act synergistically and lead to pathological microglial activation. Microglial overactivation may lead to excessive synaptic pruning and loss of cortical gray matter. Microglial mediated damage to stress-sensitive regions such as the prefrontal cortex and hippocampus may lead directly to cognitive and negative symptoms, and account for a number of the structural brain changes associated with the disorder. Loss of cortical control may also lead to disinhibition of subcortical dopamine—thereby leading to positive psychotic symptoms. We review the preclinical and in vivo evidence for this model and consider the implications this has for treatment, and future directions.

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Schizophrenia associated sensory gating deficits develop after adolescent microglia activation

Cited by 37 publications

References 48 publications

Evolution of structural abnormalities in the rat brain following in utero exposure to maternal immune activation: A longitudinal in vivo MRI study

Evolution of structural abnormalities in the rat brain following in utero exposure to maternal immune activation: A longitudinal in vivo MRI study

The Neuro-endocrinological Role of Microbial Glutamate and GABA Signaling

Inflammation and the neural diathesis-stress hypothesis of schizophrenia: a reconceptualization

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