Intermittent systemic exposure to lipopolysaccharide-induced inflammation disrupts hippocampal long-term potentiation and impairs cognition in aging male mice

Engler-Chiurazzi, Elizabeth B.; Russell, Ashley E.; Povroznik, J.M.; McDonald, Katherine; Porter, Keyana N; Wang, D S; Hammock, J; Billig, B K; Felton, C C; Yilmaz, Aylin; Schreurs, Bernard G.; O'Callaghan, J D; Zwezdaryk, KJ; Simpkins, JW

doi:10.1016/j.bbi.2022.12.013

Cited by 12 publications

(6 citation statements)

References 124 publications

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“…An additional consideration associated with persistent inflammation is the increased likelihood of developing disease in the future. Chronically elevated inflammation has been associated with neurodegenerative diseases such as Parkinson’s, Alzheimer’s, and other dementias [ 10 , 11 , 12 , 61 , 62 , 63 ]. Although individuals with long COVID likely represent those with CNS inflammation and who are therefore at greater risk of future neurodegenerative disease, others with prior SARS-CoV-2 infections could also have an elevated risk.…”

Section: Discussionmentioning

confidence: 99%

Emerging Role of Kinin B1 Receptor in Persistent Neuroinflammation and Neuropsychiatric Symptoms in Mice Following Recovery from SARS-CoV-2 Infection

Sriramula,

Theobald,

Parekh

et al. 2023

Cells

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Evidence suggests that patients with long COVID can experience neuropsychiatric, neurologic, and cognitive symptoms. However, these clinical data are mostly associational studies complicated by confounding variables, thus the mechanisms responsible for persistent symptoms are unknown. Here we establish an animal model of long-lasting effects on the brain by eliciting mild disease in K18-hACE2 mice. Male and female K18-hACE2 mice were infected with 4 × 103 TCID50 of SARS-CoV-2 and, following recovery from acute infection, were tested in the open field, zero maze, and Y maze, starting 30 days post infection. Following recovery from SARS-CoV-2 infection, K18-hACE2 mice showed the characteristic lung fibrosis associated with SARS-CoV-2 infection, which correlates with increased expression of the pro-inflammatory kinin B1 receptor (B1R). These mice also had elevated expression of B1R and inflammatory markers in the brain and exhibited behavioral alterations such as elevated anxiety and attenuated exploratory behavior. Our data demonstrate that K18-hACE2 mice exhibit persistent effects of SARS-CoV-2 infection on brain tissue, revealing the potential for using this model of high sensitivity to SARS-CoV-2 to investigate mechanisms contributing to long COVID symptoms in at-risk populations. These results further suggest that elevated B1R expression may drive the long-lasting inflammatory response associated with SARS-CoV-2 infection.

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Section: Discussionmentioning

confidence: 99%

Emerging Role of Kinin B1 Receptor in Persistent Neuroinflammation and Neuropsychiatric Symptoms in Mice Following Recovery from SARS-CoV-2 Infection

Sriramula,

Theobald,

Parekh

et al. 2023

Cells

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“…Various clinical trials have found numerous changes in the brain that may explain the negative impact of unhealthy aging on cognitive abilities. Cognitive impairment during aging is associated with hormonal deficits ( Amore, 2005 ; Henderson, 2011 ; Winczyk et al, 2022 ), inflammation ( Engler-Chiurazzi et al, 2023 ; Teoh et al, 2023 ; Zhou et al, 2023 ), epigenetic modifications affecting gene expression and adult neurogenesis ( Zocher and Toda, 2023 ), and changes in the cholinergic, glutamatergic, dopaminergic, and histaminergic neurotransmission ( Gasiorowska et al, 2021 ). These changes reduce synaptic and brain plasticity and memory loss ( Shen and Barnes, 1996 ; Echeverria et al, 2017 ; Kumar et al, 2019b ; Gasiorowska et al, 2021 ; Sanchez-Sarasua et al, 2022 ).…”

Section: Memory Loss During Agingmentioning

confidence: 99%

Nicotinic acetylcholine receptors and learning and memory deficits in Neuroinflammatory diseases

2023

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Animal survival depends on cognitive abilities such as learning and memory to adapt to environmental changes. Memory functions require an enhanced activity and connectivity of a particular arrangement of engram neurons, supported by the concerted action of neurons, glia, and vascular cells. The deterioration of the cholinergic system is a common occurrence in neurological conditions exacerbated by aging such as traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), Alzheimer’s disease (AD), and Parkinson’s disease (PD). Cotinine is a cholinergic modulator with neuroprotective, antidepressant, anti-inflammatory, antioxidant, and memory-enhancing effects. Current evidence suggests Cotinine’s beneficial effects on cognition results from the positive modulation of the α7-nicotinic acetylcholine receptors (nAChRs) and the inhibition of the toll-like receptors (TLRs). The α7nAChR affects brain functions by modulating the function of neurons, glia, endothelial, immune, and dendritic cells and regulates inhibitory and excitatory neurotransmission throughout the GABA interneurons. In addition, Cotinine acting on the α7 nAChRs and TLR reduces neuroinflammation by inhibiting the release of pro-inflammatory cytokines by the immune cells. Also, α7nAChRs stimulate signaling pathways supporting structural, biochemical, electrochemical, and cellular changes in the Central nervous system during the cognitive processes, including Neurogenesis. Here, the mechanisms of memory formation as well as potential mechanisms of action of Cotinine on memory preservation in aging and neurological diseases are discussed.

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“…Peripheral injury induces activation of brain microglia and mast cells (including parenchymal and meningeal mast cells) and induces increased levels of inflammatory factors in the hypothalamus and hippocampus, decreased expression of hippocampal postsynaptic densin 95, and tight junction protein (Occludin) ( Yang J. et al, 2022 ). Sepsis induces activation of the pro-inflammatory environment and cognitive impairment in the zebrafish brain ( Nie et al, 2022 ), and prolonged intermittent LPS stimulation induces learning-memory dysfunction and elevated IL-6 expression in the frontal cortex of the brain as well as hippocampal tissues and a tendency to exhibit impaired learning in mice ( Engler-Chiurazzi et al, 2023 ). As well as silicosis model mice showed both lung inflammation and upregulation of pro-inflammatory cytokines in the mouse hippocampus, synaptic damage, Aβ accumulation, and memory impairment ( Suman et al, 2022 ).…”

Section: Mechanisms By Which Peripheral Inflammation Promotes Central...mentioning

confidence: 99%

Peripheral inflammation and neurocognitive impairment: correlations, underlying mechanisms, and therapeutic implications

Tan,

Chen,

Kong

et al. 2023

Front. Aging Neurosci.

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Cognitive impairments, such as learning and memory deficits, may occur in susceptible populations including the elderly and patients who are chronically ill or have experienced stressful events, including surgery, infection, and trauma. Accumulating lines of evidence suggested that peripheral inflammation featured by the recruitment of peripheral immune cells and the release of pro-inflammatory cytokines may be activated during aging and these conditions, participating in peripheral immune system-brain communication. Lots of progress has been achieved in deciphering the core bridging mechanism connecting peripheral inflammation and cognitive impairments, which may be helpful in developing early diagnosis, prognosis evaluation, and prevention methods based on peripheral blood circulation system sampling and intervention. In this review, we summarized the evolving evidence on the prevalence of peripheral inflammation-associated neurocognitive impairments and discussed the research advances in the underlying mechanisms. We also highlighted the prevention and treatment strategies against peripheral inflammation-associated cognitive dysfunction.

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Intermittent systemic exposure to lipopolysaccharide-induced inflammation disrupts hippocampal long-term potentiation and impairs cognition in aging male mice

Cited by 12 publications

References 124 publications

Emerging Role of Kinin B1 Receptor in Persistent Neuroinflammation and Neuropsychiatric Symptoms in Mice Following Recovery from SARS-CoV-2 Infection

Emerging Role of Kinin B1 Receptor in Persistent Neuroinflammation and Neuropsychiatric Symptoms in Mice Following Recovery from SARS-CoV-2 Infection

Nicotinic acetylcholine receptors and learning and memory deficits in Neuroinflammatory diseases

Peripheral inflammation and neurocognitive impairment: correlations, underlying mechanisms, and therapeutic implications

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