Induction of Microglia Activation after Infection with the Non-Neurotropic A/CA/04/2009 H1N1 Influenza Virus

Sadasivan, Shankar; Zanin, Mark; O’Brien, Kevin; Schultz‐Cherry, Stacey; Smeyne, Richard J.

doi:10.1371/journal.pone.0124047

Cited by 88 publications

(97 citation statements)

References 65 publications

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“…Microglia were classified as activated if the cell body was visibly increased in diameter and the cell had shortened and thickened processes. Microglia were classified as resting if they had a small cell body (≤3μm) and longer, thinner processes [32]. The number of microglia in the right and left SNpc were summed to provide an estimate of the total number of resting and active microglia in the SNpc.…”

Section: Methodsmentioning

confidence: 99%

Assessment of the Effects of MPTP and Paraquat on Dopaminergic Neurons and Microglia in the Substantia Nigra Pars Compacta of C57BL/6 Mice

et al. 2016

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The neurotoxicity of paraquat dichloride (PQ) was assessed in two inbred strains of 9- or 16-week old male C57BL/6 mice housed in two different laboratories and compared to the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). PQ was administered by intraperitoneal injections; either once (20 mg/kg) or twice (10 mg/kg) weekly for 3 weeks, while MPTP-HCl was injected 4 times on a single day (20 mg/kg/dose). Brains were collected 8, 16, 24, 48, 96 or 168 hours after the last PQ treatment, and 48 or 168 hours after MPTP treatment. Dopamine neurons in the substantia nigra pars compacta (SNpc) were identified by antibodies to tyrosine hydroxylase (TH+) and microglia were identified using Iba-1 immunoreactivity. The total number of TH+ neurons and the number of resting and activated microglia in the SNpc at 168 hours after the last dose were estimated using model- or design-based stereology, with investigators blinded to treatment. In a further analysis, a pathologist, also blinded to treatment, evaluated the SNpc and/or striatum for loss of TH+ neurons (SNpc) or terminals (striatum), cell death (as indicated by amino cupric silver uptake, TUNEL and/or caspase 3 staining) and neuroinflammation (as indicated by Iba-1 and/or GFAP staining). PQ, administered either once or twice weekly to 9- or 16-week old mice from two suppliers, had no effect on the number of TH+ neurons or microglia in the SNpc, as assessed by two groups, each blinded to treatment, using different stereological methods. PQ did not induce neuronal cell loss or degeneration in the SNpc or striatum. Additionally, there was no evidence of apoptosis, microgliosis or astrogliosis. In MPTP-treated mice, the number of TH+ neurons in the SNpc was significantly decreased and the number of activated microglia increased. Histopathological assessment found degenerating neurons/terminals in the SNpc and striatum but no evidence of apoptotic cell death. MPTP activated microglia in the SNpc and increased the number of astrocytes in the SNpc and striatum.

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Section: Methodsmentioning

confidence: 99%

Assessment of the Effects of MPTP and Paraquat on Dopaminergic Neurons and Microglia in the Substantia Nigra Pars Compacta of C57BL/6 Mice

et al. 2016

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“…This suggests that H5N1 brain infection can lead to long-lasting effects that could contribute to pathological processes observed in diseases such as Parkinson’s disease. Recently, this same group has reported microglial activation in the CNS of mice infected with pandemic 2009 strains of H1N1 IAV in absence of CNS IAV infection (101). This may be a common outcome after systemic infection with any virus without neurotropism.…”

Section: Influenza a Virusmentioning

confidence: 99%

Emerging Infections of CNS: Avian Influenza A Virus, Rift Valley Fever Virus and Human Parechovirus

et al. 2015

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History is replete with emergent pandemic infections that have decimated the human population. Given the shear mass of humans that now crowd the earth, there is every reason to suspect history will repeat itself. We describe three RNA viruses that have recently emerged in the human population to mediate severe neurological disease. These new diseases are results of new mutations in the infectious agents or new exposure pathways to the agents or both. To appreciate their pathogenesis, we summarize the essential virology and immune response to each agent. Infection is described in the context of known host defenses. Once the viruses evade immune defenses and enter CNS cells, they rapidly co-opt host RNA processing to a cataclysmic extent. It is not clear why the brain is particularly susceptible to RNA viruses; but perhaps because of its tremendous dependence on RNA processing for physiological functioning, classical mechanisms of host defense (e.g. interferon disruption of viral replication) are diminished or not available. Effectiveness of immunity, immunization and pharmacological therapies is reviewed to contextualize the scope of the public health challenge. Unfortunately, vaccines that confer protection from systemic disease do not necessarily confer protection for the brain after exposure through unconventional routes.

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“…Influenza strain targets also differ. Notably, the H5N1 virus and other avianderived strains are neurotropic while H1N1 is thought not to be (76)(77)(78).…”

Section: Reconciling Maternal Infection With Influenza With the Neuromentioning

confidence: 99%

Schizophrenia and Influenza at the Centenary of the 1918-1919 Spanish Influenza Pandemic: Mechanisms of Psychosis Risk

et al. 2020

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Associations between influenza infection and psychosis have been reported since the eighteenth century, with acute "psychoses of influenza" documented during multiple pandemics. In the late 20 th century, reports of a season-of-birth effect in schizophrenia were supported by large-scale ecological and sero-epidemiological studies suggesting that maternal influenza infection increases the risk of psychosis in offspring. We examine the evidence for the association between influenza infection and schizophrenia risk, before reviewing possible mechanisms via which this risk may be conferred. Maternal immune activation models implicate placental dysfunction, disruption of cytokine networks, and subsequent microglial activation as potentially important pathogenic processes. More recent neuroimmunological advances focusing on neuronal autoimmunity following infection provide the basis for a model of infection-induced psychosis, potentially implicating autoimmunity to schizophrenia-relevant protein targets including the Nmethyl-D-aspartate receptor. Finally, we outline areas for future research and relevant experimental approaches and consider whether the current evidence provides a basis for the rational development of strategies to prevent schizophrenia.

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Induction of Microglia Activation after Infection with the Non-Neurotropic A/CA/04/2009 H1N1 Influenza Virus

Cited by 88 publications

References 65 publications

Assessment of the Effects of MPTP and Paraquat on Dopaminergic Neurons and Microglia in the Substantia Nigra Pars Compacta of C57BL/6 Mice

Assessment of the Effects of MPTP and Paraquat on Dopaminergic Neurons and Microglia in the Substantia Nigra Pars Compacta of C57BL/6 Mice

Emerging Infections of CNS: Avian Influenza A Virus, Rift Valley Fever Virus and Human Parechovirus

Schizophrenia and Influenza at the Centenary of the 1918-1919 Spanish Influenza Pandemic: Mechanisms of Psychosis Risk

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