Poly I:C‐induced maternal immune challenge reduces perineuronal net area and raises spontaneous network activity of hippocampal neurons in vitro

Wegrzyn, David; Manitz, Marie-Pierre; Kostka, Michael; Freund, Nadja; Juckel, Georg; Faissner, Andréas

doi:10.1111/ejn.14934

Cited by 13 publications

(12 citation statements)

References 96 publications

(128 reference statements)

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“…Similarly, a reduced firing frequency and increased amplitudes of miniature excitatory postsynaptic currents (mEPSPs) in the hippocampal CA1-region of mice derived from Poly I:C- treated dams could be observed in hippocampal slices [ 206 ]. In addition, dissociated hippocampal neurons isolated from embryonic mice of Poly I:C-treated dams developed a network hyperactivity and disruptions of perineuronal nets (PNNs), as well as reduced soma areas of PNN-wearing neurons in vitro [ 207 ]. PNNs are a specialized and condensed form of the extracellular matrix (ECM) that stabilize synaptic contacts but prevent the formation of new connections [ 208 ].…”

Section: Structural and Functional Hippocampus Deviations In Animal M...mentioning

confidence: 99%

Structural and Functional Deviations of the Hippocampus in Schizophrenia and Schizophrenia Animal Models

Wegrzyn

Juckel

Faissner

2022

IJMS

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Schizophrenia is a grave neuropsychiatric disease which frequently onsets between the end of adolescence and the beginning of adulthood. It is characterized by a variety of neuropsychiatric abnormalities which are categorized into positive, negative and cognitive symptoms. Most therapeutical strategies address the positive symptoms by antagonizing D2-dopamine-receptors (DR). However, negative and cognitive symptoms persist and highly impair the life quality of patients due to their disabling effects. Interestingly, hippocampal deviations are a hallmark of schizophrenia and can be observed in early as well as advanced phases of the disease progression. These alterations are commonly accompanied by a rise in neuronal activity. Therefore, hippocampal formation plays an important role in the manifestation of schizophrenia. Furthermore, studies with animal models revealed a link between environmental risk factors and morphological as well as electrophysiological abnormalities in the hippocampus. Here, we review recent findings on structural and functional hippocampal abnormalities in schizophrenic patients and in schizophrenia animal models, and we give an overview on current experimental approaches that especially target the hippocampus. A better understanding of hippocampal aberrations in schizophrenia might clarify their impact on the manifestation and on the outcome of this severe disease.

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Section: Structural and Functional Hippocampus Deviations In Animal M...mentioning

confidence: 99%

Structural and Functional Deviations of the Hippocampus in Schizophrenia and Schizophrenia Animal Models

Wegrzyn

Juckel

Faissner

2022

IJMS

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“…The culturing of primary hippocampal neurons was performed, as previously described (Gottschling et al, 2016;Wegrzyn et al, 2020). The hippocampi of embryonic stage 15.5 (E15.5) mice were isolated and collected in 1 ml dissection medium [(HBSS, Thermo Fisher Scientific Inc.;Cat.…”

Section: Culturing Of Primary Hippocampal Neuronsmentioning

confidence: 99%

“…PNN area sizes were quantified using the "Freehand Selections" tool in ImageJ after defining a distance length depending on the scale bar. The fluorescence intensity of PNNs was analyzed by measuring the mean gray value and on the other hand by determining the total corrected total cell fluorescence (CTCF), as previously described (McCloy et al, 2014;Wegrzyn et al, 2020).…”

Section: Data Quantificationmentioning

confidence: 99%

Poly I:C Activated Microglia Disrupt Perineuronal Nets and Modulate Synaptic Balance in Primary Hippocampal Neurons in vitro

Wegrzyn

Freund

Faissner

et al. 2021

Front. Synaptic Neurosci.

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Perineuronal nets (PNNs) are specialized, reticular structures of the extracellular matrix (ECM) that can be found covering the soma and proximal dendrites of a neuronal subpopulation. Recent studies have shown that PNNs can highly influence synaptic plasticity and are disrupted in different neuropsychiatric disorders like schizophrenia. Interestingly, there is a growing evidence that microglia can promote the loss of PNNs and contribute to neuropsychiatric disorders. Based on this knowledge, we analyzed the impact of activated microglia on hippocampal neuronal networks in vitro. Therefore, primary cortical microglia were cultured and stimulated via polyinosinic-polycytidylic acid (Poly I:C; 50 μg/ml) administration. The Poly I:C treatment induced the expression and secretion of different cytokines belonging to the CCL- and CXCL-motif chemokine family as well as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In addition, the expression of matrix metalloproteinases (MMPs) could be verified via RT-PCR analysis. Embryonic hippocampal neurons were then cultured for 12 days in vitro (DIV) and treated for 24 h with microglial conditioned medium. Interestingly, immunocytochemical staining of the PNN component Aggrecan revealed a clear disruption of PNNs accompanied by a significant increase of glutamatergic and a decrease of γ-aminobutyric acid-(GABA)ergic synapse numbers on PNN wearing neurons. In contrast, PNN negative neurons showed a significant reduction in both, glutamatergic and GABAergic synapses. Electrophysiological recordings were performed via multielectrode array (MEA) technology and unraveled a significantly increased spontaneous network activity that sustained also 24 and 48 h after the administration of microglia conditioned medium. Taken together, we could observe a strong impact of microglial secreted factors on PNN integrity, synaptic plasticity and electrophysiological properties of cultured neurons. Our observations might enhance the understanding of neuron-microglia interactions considering the ECM.

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“…Wegrzyn et al. (2020) from the Faissner group provide insights into the ECM and cellular mechanisms of the maternal immune system during gestation, which is well known to be linked to neuropsychiatric diseases like schizophrenia. By using behavioral tests, primary astrocytic and neuronal cell cultures, immunocytochemistry and electrophysiological recordings, the researchers observed that treatment with polyinosinic‐polycytidylic acid sodium salt (Poly I:C), a model of viral infection, resulted in impairment of prepulse inhibition, a significantly reduced axonal complexity and a significant reduction of the major ECM molecule aggrecan with regard to staining intensity, area and soma size.…”

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confidence: 99%

Brain extracellular matrix: An upcoming target in neurological and psychiatric disorders

Dityatev

Seidenbecher

Morawski

2021

Eur J of Neuroscience

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Poly I:C‐induced maternal immune challenge reduces perineuronal net area and raises spontaneous network activity of hippocampal neurons in vitro

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 13 publications

References 96 publications

Structural and Functional Deviations of the Hippocampus in Schizophrenia and Schizophrenia Animal Models

Structural and Functional Deviations of the Hippocampus in Schizophrenia and Schizophrenia Animal Models

Poly I:C Activated Microglia Disrupt Perineuronal Nets and Modulate Synaptic Balance in Primary Hippocampal Neurons in vitro

Brain extracellular matrix: An upcoming target in neurological and psychiatric disorders

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