Early life exposure to poly I:C impairs striatal DA-D2 receptor binding, myelination and associated behavioural abilities in rats

Singh, Brijendra; Dhuriya, Yogesh K.; Patro, Nisha; Thakur, M. K.; Khanna, Vinay K.; Patro, Nisha

doi:10.1016/j.jchemneu.2021.102035

Cited by 3 publications

(2 citation statements)

References 90 publications

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“…When neonatal rats were administered poly I:C intraperitoneally, reduced white matter density and slow myelin development were observed. Moreover, 12 weeks post-treatment, elevation of tnfa and downregulation of bdnf , arc (activity regulated cytoskeleton associated protein), and egr1 (early growth response 1) mRNA (associated with neurodevelopment) in the hippocampus was observed, resulting in poor memory, motor activity, and coordination [ 105 , 106 ]. One of the recent studies demonstrated that, in patients with schizophrenia having exposure to childhood trauma, IL-6 played a role in mediating the biological events leading to social cognitive deficits [ 107 ].…”

Section: The Role Of Toll-like Receptors In Schizophreniamentioning

confidence: 99%

Counting the Toll of Inflammation on Schizophrenia—A Potential Role for Toll-like Receptors

Patlola,

Donohoe,

McKernan

2023

Biomolecules

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Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRRs) that are ubiquitously expressed in the human body. They protect the brain and central nervous system from self and foreign antigens/pathogens. The immune response elicited by these receptors culminates in the release of cytokines, chemokines, and interferons causing an inflammatory response, which can be both beneficial and harmful to neurodevelopment. In addition, the detrimental effects of TLR activation have been implicated in multiple neurodegenerative diseases such as Alzheimer’s, multiple sclerosis, etc. Many studies also support the theory that cytokine imbalance may be involved in schizophrenia, and a vast amount of literature showcases the deleterious effects of this imbalance on cognitive performance in the human population. In this review, we examine the current literature on TLRs, their potential role in the pathogenesis of schizophrenia, factors affecting TLR activity that contribute towards the risk of schizophrenia, and lastly, the role of TLRs and their impact on cognitive performance in schizophrenia.

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Section: The Role Of Toll-like Receptors In Schizophreniamentioning

confidence: 99%

Counting the Toll of Inflammation on Schizophrenia—A Potential Role for Toll-like Receptors

Patlola,

Donohoe,

McKernan

2023

Biomolecules

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“… 37 In nonhuman primates and mouse models, maternal immune activation induces mild inflammation and is known to cause SZ-related behavior (in early adulthood), demyelination, and alterations in synaptic and oligodendrocyte-related gene expression. 57 , 58 In a meta-analysis, obstetric complications were shown to be a risk factor for SZ 59 and to be accompanied by white matter injury, inflammation, impaired OL maturation, and myelin damage. 60 In addition, disturbances in myelination caused by stress during neurodevelopment have been hypothesized to play an essential role in SZ.…”

Section: Introductionmentioning

confidence: 99%

Disturbed Oligodendroglial Maturation Causes Cognitive Dysfunction in Schizophrenia: A New Hypothesis

Falkai

Rossner

Raabe

et al. 2023

Schizophrenia Bulletin

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Background and Hypothesis Cognitive impairment is a hallmark of schizophrenia, but no effective treatment is available to date. The underlying pathophysiology includes disconnectivity between hippocampal and prefrontal brain regions. Supporting evidence comes from diffusion-weighted imaging studies that suggest abnormal organization of frontotemporal white matter pathways in schizophrenia. Study Design Here, we hypothesize that in schizophrenia, deficient maturation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes substantially contributes to abnormal frontotemporal macro- and micro-connectivity and subsequent cognitive deficits. Study Results Our postmortem studies indicate a reduced oligodendrocyte number in the cornu ammonis 4 (CA4) subregion of the hippocampus, and others have reported the same histopathological finding in the dorsolateral prefrontal cortex. Our series of studies on aerobic exercise training showed a volume increase in the hippocampus, specifically in the CA4 region, and improved cognition in individuals with schizophrenia. The cognitive effects were subsequently confirmed by meta-analyses. Cell-specific schizophrenia polygenic risk scores showed that exercise-induced CA4 volume increase significantly correlates with OPCs. From animal models, it is evident that early life stress and oligodendrocyte-related gene variants lead to schizophrenia-related behavior, cognitive deficits, impaired oligodendrocyte maturation, and reduced myelin thickness. Conclusions Based on these findings, we propose that pro-myelinating drugs (e.g., the histamine blocker clemastine) combined with aerobic exercise training may foster the regeneration of myelin plasticity as a basis for restoring frontotemporal connectivity and cognition in schizophrenia.

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THC improves behavioural schizophrenia-like deficits that CBD fails to overcome: a comprehensive multilevel approach using the Poly I:C maternal immune activation

Lamanna-Rama,

Romero-Miguel,

Casquero-Veiga

et al. 2024

Psychiatry Research

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Early life exposure to poly I:C impairs striatal DA-D2 receptor binding, myelination and associated behavioural abilities in rats

Cited by 3 publications

References 90 publications

Counting the Toll of Inflammation on Schizophrenia—A Potential Role for Toll-like Receptors

Counting the Toll of Inflammation on Schizophrenia—A Potential Role for Toll-like Receptors

Disturbed Oligodendroglial Maturation Causes Cognitive Dysfunction in Schizophrenia: A New Hypothesis

THC improves behavioural schizophrenia-like deficits that CBD fails to overcome: a comprehensive multilevel approach using the Poly I:C maternal immune activation

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