Pharmacological and proteomic analyses of neonatal polyI:C-treated adult mice

Kitagawa, Kanako; Nagai, Taku; Yamada, Kiyofumi

doi:10.1016/j.neures.2018.10.007

Cited by 8 publications

(6 citation statements)

References 43 publications

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“…repeated injection with on GD15-17 Decrease pre-synaptic protein expression and altered electrophysiological synaptic functions in juvenile offspring McColl et al, 2019 [183] i.p. injection with poly(I:C) on GD14 Increased mRNA expression of several amino acid transporters in the placenta and fetal brain; decrease in protein levels of ASCT1 and EAAT2 in placenta; decrease of protein levels of SNAT5, EAAT1, and GLYT1 in fetal brain Kitagawa et al, 2019 [160] repeated s.c. injection with poly(I:C) on post-natal days 2-6 PPI deficit, emotional and cognitive dysfunction in the offspring; changes in the protein expression of ALDH1L1 and CRMP5 (astrocyte-neuron interaction molecules) in the hippocampus Ozawa et al, 2005 [174] repeated i.p. injection with poly(I:C) from E12 to E17…”

Section: Animal Inflammatory Models Of Schizophreniamentioning

confidence: 99%

“…PPI deficits are therefore assumed to be a hallmark feature of animal models of schizophrenia and are evident in both adult and juvenile MIA animals [ 158 ]. Furthermore, to support the relevance of MIA models to the pathophysiology of schizophrenia, it has been observed that PPI deficits are reversed by acute or chronic antipsychotic treatment with haloperidol, olanzapine, risperidone, and clozapine in adolescent or adult rodents [ 159 , 160 ]. Similarly, another measure of information gating, also known as “latent inhibition,” appears to be disrupted in the adult offspring of dams challenged with poly(I:C).…”

Section: Animal Inflammatory Models Of Schizophreniamentioning

confidence: 99%

“…Moreover, microglia activation following maternal poly(I:C) challenges may be more pronounced in male than female offspring, mirroring the higher incidence of schizophrenia in males as well as more severe clinical features [ 167 , 168 ]. Proteomic analysis of poly(I:C)-treated rodents showed significant changes in the protein expression of 10-formyltetrahydrofolate dehydrogenase (ALDH1L1) and collapsin response mediator protein 5 (CRMP5) [ 160 ]. More specifically, ALDH1L1 is an enzyme converting 10-formyl-tetrahydrofolate to tetrahydrofolate and carbon dioxide in a NADP + -dependent reaction, which is expressed in glial cells and astrocytes and has been found to increase in schizophrenia patients [ 169 ].…”

Section: Animal Inflammatory Models Of Schizophreniamentioning

confidence: 99%

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Linking Inflammation, Aberrant Glutamate-Dopamine Interaction, and Post-synaptic Changes: Translational Relevance for Schizophrenia and Antipsychotic Treatment: a Systematic Review

Bartolomeis¹,

Barone²,

Vellucci³

et al. 2022

Mol Neurobiol

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Evidence from clinical, preclinical, and post-mortem studies supports the inflammatory/immune hypothesis of schizophrenia pathogenesis. Less evident is the link between the inflammatory background and two well-recognized functional and structural findings of schizophrenia pathophysiology: the dopamine-glutamate aberrant interaction and the alteration of dendritic spines architecture, both believed to be the “quantal” elements of cortical-subcortical dysfunctional network. In this systematic review, we tried to capture the major findings linking inflammation, aberrant glutamate-dopamine interaction, and post-synaptic changes under a direct and inverse translational perspective, a paramount picture that at present is lacking. The inflammatory effects on dopaminergic function appear to be bidirectional: the inflammation influences dopamine release, and dopamine acts as a regulator of discrete inflammatory processes involved in schizophrenia such as dysregulated interleukin and kynurenine pathways. Furthermore, the link between inflammation and glutamate is strongly supported by clinical studies aimed at exploring overactive microglia in schizophrenia patients and maternal immune activation models, indicating impaired glutamate regulation and reduced N-methyl-D-aspartate receptor (NMDAR) function. In addition, an inflammatory/immune-induced alteration of post-synaptic density scaffold proteins, crucial for downstream NMDAR signaling and synaptic efficacy, has been demonstrated. According to these findings, a significant increase in plasma inflammatory markers has been found in schizophrenia patients compared to healthy controls, associated with reduced cortical integrity and functional connectivity, relevant to the cognitive deficit of schizophrenia. Finally, the link between altered inflammatory/immune responses raises relevant questions regarding potential new therapeutic strategies specifically for those forms of schizophrenia that are resistant to canonical antipsychotics or unresponsive to clozapine.

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Section: Animal Inflammatory Models Of Schizophreniamentioning

confidence: 99%

Section: Animal Inflammatory Models Of Schizophreniamentioning

confidence: 99%

Section: Animal Inflammatory Models Of Schizophreniamentioning

confidence: 99%

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Linking Inflammation, Aberrant Glutamate-Dopamine Interaction, and Post-synaptic Changes: Translational Relevance for Schizophrenia and Antipsychotic Treatment: a Systematic Review

Bartolomeis¹,

Barone²,

Vellucci³

et al. 2022

Mol Neurobiol

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“…In this context, studies have shown that the prefrontal cortex and hippocampus microglia are activated in the offspring of PolyI:C rat models, which indicates that microglial activation may contribute to the pathogenesis of schizophrenia (Li et al, 2018). Another recent study has found increase in the expression of aldehyde dehydrogenase family 1 member L1 (ALDH1L1) while the expression of collagen response mediator protein 5 (CRMP5) has decreased in the hippocampus of mice treated with PolyI:C, suggesting that astrocytes are associated with the interaction of neurons, which play a role in the pathophysiology of neurodevelopmental disorders induced by immune activation in neonates (Kitagawa, Nagai, & Yamada, 2019). It is worth noting that the PolyI:C model has also been utilized to study other psychiatric diseases such as autism but it lacks specificity for those diseases.…”

Section: Neurodevelopmental Animal Experimental Modelmentioning

confidence: 99%

Application of animal experimental models in the research of schizophrenia

Wang

Zhao

et al. 2021

American J of Med Genetics Pt B

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Schizophrenia is a relatively common but serious mental illness that results in a heavy burden to patients, their families, and society. The disease can be triggered by multiple factors, while the specific pathogenesis remains unclear. The development of effective therapeutic drugs for schizophrenia relies on a comprehensive understanding of the basic biology and pathophysiology of the disease. Therefore, effective animal experimental models play a vital role in the study of schizophrenia. Based on different molecular mechanisms and modeling methods, the currently used experimental animal experimental models of schizophrenia can be divided into four categories that can better simulate the clinical symptoms and the interplay between susceptible genes and the environment: neurodevelopmental, drug‐induced, genetic‐engineering, and genetic‐environmental interaction of animal experimental models. Each of these categories contains multiple subtypes, which has its own advantages and disadvantages and therefore requires careful selection in a research application. The emergence and utilization of these models are promising in the prediction of the risk of schizophrenia at the molecular level, which will shed light on effective and targeted treatment at the genetic level.

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“…To elucidate the relationships between these behavioral changes in sH-2D-expressing mice and the clinical symptoms of mental diseases, the effects of clozapine (5.0 mg/kg; oral administration), an atypical antipsychotic drug, were analyzed. sH-2D-expressing mice were treated with clozapine 60 min before the tasks [35]. In the social interaction test, clozapine signi cantly attenuated dysfunctions in social activity in sH-2D-expressing mice, while the same treatment had negligible effects on social behavior in control mice (group, F(1, 33) = 17.4, p < 0.0001; trials, F(3, 99) = 88.3, p < 0.0001; treatment, F(1, 33) = 1.15, p = 0.2911; trials × AAV-type, F(3, 99) = 10.7, p < 0.0001; trials × Treatment, F(3, 99) = 0.44, p = 0.6100; group × treatment, F(1, 33) = 12.6, p < 0.0001); trials × group × treatment, F(3, 99) = 6.11, p < 0.0001; Fig.…”

Section: Effects Of Clozapine On Behavioral De Cits In Sh-2dexpressinmentioning

confidence: 99%

Overexpression of Astroglial Major Histocompatibility Complex Class I in the Medial Prefrontal Cortex Impairs Visual Discrimination Learning in Mice

Wulaer

Hada

Sobue

et al. 2020

Preprint

Self Cite

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Background Immune molecules, such as cytokines, complement, and major histocompatibility complex (MHC) proteins, in the central nervous system are often associated with neuropsychiatric disorders. Neuronal MHC class I (MHCI), such as H-2D, regulate neurite outgrowth, the establishment and function of cortical connections, and activity-dependent refinement in mice. We previously established mice expressing MHCI specifically in astrocytes of the media prefrontal cortex (mPFC) using the adeno-associated virus (AAV) vector under the control of the glial fibrillary acidic protein (GFAP) promoter. Mice expressing the soluble form of H-2D (sH-2D) in the mPFC (sH-2D-expressing mice) showed abnormal behaviors, including social interaction deficits and cognitive dysfunctions. However, the pathophysiological significance of astroglial MHCI on higher brain functions remains unclear. Therefore, cognitive function in mice expressing sH-2D in astrocytes of the mPFC was tested using the visual discrimination (VD) task to assess the impact of the astrocyte pathology and resulting behavioral changes.Methods Three separate batches of mice were used in the present study. sH-2D-expressing mice were subjected to the VD and reversal learning tasks, morphological analyses, and pharmacological intervention using clozapine in the social interaction and novel object recognition tasks.Results In pretraining, the performance of sH-2D-expressing mice was normal in response phase sessions (stages 1–4), but impaired in the punish phase session (stage 5). The total numbers of sessions, trials, normal trials, and correction trials to reach the VD criterion were significantly higher in sH-2D-expressing mice than in control mice. A morphological study showed that dendritic complexity was significantly reduced in the dorsal striatum of sH-2D-expressing mice. A treatment with clozapine ameliorated decreased social behavior as well as impaired object recognition memory in sH-2D-expressing mice.Conclusion Collectively, the present results suggest that the overexpression of astroglial MHCI in the mPFC results in impaired VD learning, which may be accompanied by decreased dendritic complexity in the dorsal striatum and mPFC.

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Pharmacological and proteomic analyses of neonatal polyI:C-treated adult mice

Cited by 8 publications

References 43 publications

Linking Inflammation, Aberrant Glutamate-Dopamine Interaction, and Post-synaptic Changes: Translational Relevance for Schizophrenia and Antipsychotic Treatment: a Systematic Review

Linking Inflammation, Aberrant Glutamate-Dopamine Interaction, and Post-synaptic Changes: Translational Relevance for Schizophrenia and Antipsychotic Treatment: a Systematic Review

Application of animal experimental models in the research of schizophrenia

Overexpression of Astroglial Major Histocompatibility Complex Class I in the Medial Prefrontal Cortex Impairs Visual Discrimination Learning in Mice

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