P300 Repetitive magnetic stimulation reverses the synaptic phenotype of cultured rat CA1 pyramidal neurons in a maternal immune activation model of schizophrenia

2017 ◽  
Vol 128 (3) ◽  
pp. e157-e158
Author(s):  
C. Galanis ◽  
M. Lenz ◽  
V. Aliane ◽  
K. Funke ◽  
A. Vlachos
Keyword(s):  
Immune Activation ◽  
Magnetic Stimulation ◽  
Pyramidal Neurons ◽  
Activation Model ◽  
Maternal Immune Activation ◽  
Ca1 Pyramidal Neurons ◽  
Repetitive Magnetic Stimulation

scholarly journals Microglia mediate synaptic plasticity induced by 10 Hz repetitive magnetic stimulation

2021 ◽  
Author(s):  
Amelie Eichler ◽  
Dimitrios Kleidonas ◽  
Zsolt Turi ◽  
Matthias Kirsch ◽  
Dietmar Pfeifer ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Functional Properties ◽  
Magnetic Stimulation ◽  
Pyramidal Neurons ◽  
Therapeutic Effects ◽  
Tissue Cultures ◽  
Ca1 Pyramidal Neurons ◽  
Structural And Functional Properties ◽  
Repetitive Magnetic Stimulation

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that is widely used in clinical practice for therapeutic purposes. Nevertheless, the mechanisms that mediate its therapeutic effects remain poorly understood. Recent work implicates that microglia, the resident immune cells of the central nervous system, have a defined role in the regulation of physiological brain function, e.g. the expression of synaptic plasticity. Despite this observation, no evidence exists for a role of microglia in excitatory synaptic plasticity induced by rTMS. Here, we used repetitive magnetic stimulation of organotypic entorhino-hippocampal tissue cultures to test for the role of microglia in synaptic plasticity induced by 10 Hz repetitive magnetic stimulation (rMS). For this purpose, we performed PLX3397 (Pexidartinib) treatment to deplete microglia from tissue culture preparations. Using whole-cell patch-clamp recordings, live-cell microscopy, immunohistochemistry and transcriptome analysis, we assessed structural and functional properties of both CA1 pyramidal neurons and microglia to correlate the microglia phenotype to synaptic plasticity. PLX3397 treatment over 18 days reliably depletes microglia in tissue cultures, without affecting structural and functional properties of CA1 pyramidal neurons. Microglia-depleted cultures display defects in the ability of CA1 pyramidal neurons to express plasticity of excitatory synapses upon rMS. Notably, rMS induces a moderate release of proinflammatory and plasticity-promoting factors, while microglial morphology stays unaltered. We conclude that microglia play a crucial role in rMS-induced excitatory synaptic plasticity.

Repetitive magnetic stimulation induces plasticity of excitatory postsynapses on proximal dendrites of cultured mouse CA1 pyramidal neurons

2014 ◽  
Vol 220 (6) ◽  
pp. 3323-3337 ◽  
Author(s):  
Maximilian Lenz ◽  
Steffen Platschek ◽  
Viola Priesemann ◽  
Denise Becker ◽  
Laurent M. Willems ◽  
...  
Keyword(s):  
Magnetic Stimulation ◽  
Pyramidal Neurons ◽  
Ca1 Pyramidal Neurons ◽  
Repetitive Magnetic Stimulation

Impaired discrimination of a subanesthetic dose of ketamine in a maternal immune activation model of schizophrenia risk

2021 ◽  
pp. 026988112110297
Author(s):  
Wayne Meighan ◽  
Thomas W Elston ◽  
David Bilkey ◽  
Ryan D Ward
Keyword(s):  
Animal Models ◽  
Drug Discrimination ◽  
Immune Activation ◽  
Internal State ◽  
Nmda Receptor Antagonist ◽  
Activation Model ◽  
Data Link ◽  
Maternal Immune Activation ◽  
Internal States ◽  
Reliable Methods

Background: Animal models of psychiatric diseases suffer from a lack of reliable methods for accurate assessment of subjective internal states in nonhumans. This gap makes translation of results from animal models to patients particularly challenging. Aims/methods: Here, we used the drug-discrimination paradigm to allow rats that model a risk factor for schizophrenia (maternal immune activation, MIA) to report on the subjective internal state produced by a subanesthetic dose of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine. Results/outcomes: The MIA rats’ discrimination of ketamine was impaired relative to controls, both in the total number of rats that acquired and the asymptotic level of discrimination accuracy. This deficit was not due to a general inability to learn to discriminate an internal drug cue or internal state generally, as MIA rats were unimpaired in the learning and acquisition of a morphine drug discrimination and were as sensitive to the internal state of satiety as controls. Furthermore, the deficit was not due to a decreased sensitivity to the physiological effects of ketamine, as MIA rats showed increased ketamine-induced locomotor activity. Finally, impaired discrimination of ketamine was only seen at subanesthetic doses which functionally correspond to psychotomimetic doses in humans. Conclusion: These data link changes in NMDA responses to the MIA model. Furthermore, they confirm the utility of the drug-discrimination paradigm for future inquiries into the subjective internal state produced in models of schizophrenia and other developmental diseases.

scholarly journals Changes in Astroglial Markers in a Maternal Immune Activation Model of Schizophrenia in Wistar Rats are Dependent on Sex

2015 ◽  
Vol 9 ◽  
Author(s):  
Daniela F. de Souza ◽  
Krista M. Wartchow ◽  
Paula S. Lunardi ◽  
Giovana Brolese ◽  
Lucas S. Tortorelli ◽  
...  
Keyword(s):  
Immune Activation ◽  
Wistar Rats ◽  
Activation Model ◽  
Maternal Immune Activation

scholarly journals Maternal immune activation induces methylation changes in schizophrenia genes

2022 ◽  
Author(s):  
Tom Johnson ◽  
Defne Saatci ◽  
Lahiru Handunnetthi
Keyword(s):  
Environmental Risk ◽  
Immune Activation ◽  
Pyramidal Neurons ◽  
Fold Change ◽  
Adult Brain ◽  
Maternal Immune Activation ◽  
Differentially Methylated Genes ◽  
A Cell ◽  
Layer V ◽  
Upregulated Genes

Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Infection driven maternal immune activation (MIA) during pregnancy is a key environmental risk factor. However, little is known about how MIA during pregnancy could contribute to adult-onset schizophrenia. In this study, we investigated if maternal immune activation induces changes in methylation of genes linked to schizophrenia. We found that differentially expressed genes in schizophrenia brain were significantly enriched among MIA induced differentially methylated genes in the foetal brain in a cell-type-specific manner. Upregulated genes in layer V pyramidal neurons were enriched among hypomethylated genes at gestational day 9 (fold change = 1.57 , FDR = 0.049) and gestational day 17 (fold change = 1.97 , FDR = 0.0006). We also found that downregulated genes in GABAergic Rosehip interneurons were enriched among hypermethylated genes at gestational day 17 (fold change = 1.62, FDR= 0.03). Collectively, our results highlight a connection between MIA driven methylation changes during gestation and schizophrenia gene expression signatures in the adult brain. These findings carry important implications for early preventative strategies in schizophrenia.

scholarly journals The GABA Developmental Shift Is Abolished by Maternal Immune Activation Already at Birth

2018 ◽  
Vol 29 (9) ◽  
pp. 3982-3992 ◽  
Author(s):  
Amandine Fernandez ◽  
Camille Dumon ◽  
Damien Guimond ◽  
Roman Tyzio ◽  
Paolo Bonifazi ◽  
...  
Keyword(s):  
Immune Activation ◽  
Pyramidal Neurons ◽  
Experimental Studies ◽  
Network Activity ◽  
Hippocampal Pyramidal Neurons ◽  
Pairwise Correlation ◽  
Maternal Immune Activation ◽  
Postsynaptic Currents ◽  
Developmental Shift ◽  
Excitatory Action

Abstract Epidemiological and experimental studies suggest that maternal immune activation (MIA) leads to developmental brain disorders, but whether the pathogenic mechanism impacts neurons already at birth is not known. We now report that MIA abolishes in mice the oxytocin-mediated delivery γ-aminobutyric acid (GABA) shift from depolarizing to hyperpolarizing in CA3 pyramidal neurons, and this is restored by the NKCC1 chloride importer antagonist bumetanide. Furthermore, MIA hippocampal pyramidal neurons at birth have a more exuberant apical arbor organization and increased apical dendritic length than age-matched controls. The frequency of spontaneous glutamatergic postsynaptic currents is also increased in MIA offspring, as well as the pairwise correlation of the synchronized firing of active cells in CA3. These alterations produced by MIA persist, since at P14–15 GABA action remains depolarizing, produces excitatory action, and network activity remains elevated with a higher frequency of spontaneous glutamatergic postsynaptic currents. Therefore, the pathogenic actions of MIA lead to important morphophysiological and network alterations in the hippocampus already at birth.

NOX1/NADPH oxidase affects the development of autism-like behaviors in a maternal immune activation model

2021 ◽  
Vol 534 ◽  
pp. 59-66
Author(s):  
Xueqing Zhang ◽  
Masakazu Ibi ◽  
Ryu Haga ◽  
Kazumi Iwata ◽  
Misaki Matsumoto ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Immune Activation ◽  
Activation Model ◽  
Maternal Immune Activation
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