Cytokines and olfactory bulb microglia in response to bacterial challenge in the compromised primary olfactory pathway

Herbert, Rosalind P.; Harris, Julie A.; Chong, Kim Pei; Chapman, Jamie; West, Adrian K.; Chuah, Mi

doi:10.1186/1742-2094-9-109

Cited by 56 publications

(59 citation statements)

References 44 publications

(54 reference statements)

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“…However, following mild detergent damage to the nasal epithelium of C57BL/6 mice, intranasally delivered S. aureus was detected in the olfactory epithelium, olfactory nerve, and olfactory bulb, as early as 6 h postinfection (325). Indeed, damage to the olfactory epithelium within the nasal cavity appears to be an important and common event in bacterial spread to the CNS via the olfactory nerve (324)(325)(326)(327).…”

Section: Protecting the Cns From Microbial Invasion Via The Nasal Cavitymentioning

confidence: 99%

Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion

et al. 2014

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SUMMARY The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis.

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Section: Protecting the Cns From Microbial Invasion Via The Nasal Cavitymentioning

confidence: 99%

Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion

et al. 2014

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“…Hence, this potential Achilles `heel of the central nervous system is equipped with effective neuroprotective strategies to fight pathogens (Mellert et al, 1992) and to quickly regenerate after mechanical or chemical injury by rebuilding the olfactory epithelium from stem cells (Beites et al, 2005). In addition, viruses and bacteria that manage to penetrate into the olfactory bulb are efficiently detained from spreading by surrounding microglia (Kalinke et al, 2011, Herbert et al, 2012. During the course of aging, however, accumulating injuries to the olfactory system, e.g.…”

Section: Olfactory-limbic Pathways and Admentioning

confidence: 99%

Decisive role of Reelin signaling during early stages of Alzheimer’s disease

et al. 2013

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Alzheimer's disease (AD) is one of the largest unmet medical concerns of our society. Around 25 million patients worldwide together with their families are still waiting for an effective treatment. We have recently initiated a re-evaluation of our knowledge of the molecular and cellular mechanisms underlying sporadic AD. Based on the existing literature, we have proposed a mechanistic explanation of how the late-onset form of the disease may evolve on the cellular level. Here, we expand this hypothesis by addressing the pathophysiological changes underlying the early and almost invariant appearance of the neurofibrillary tangles, the only reliable correlate of the cognitive status, in distinct brain areas and their consistent "spread" along interconnected neurons as the disease advances. In this review we present and discuss novel evidence that the extracellular signaling protein Reelin, expressed along the olfactory and limbic pathways in the adult brain, might hold a key to understand the earliest steps of the disease, highlighting the olfactory pathway as the brain's Achilles heel involved in the initiation of the pathophysiological characteristic of late-onset AD. AbstractAlzheimer`s disease (AD) is one of the largest unmet medical needs of our society. Around 25 million patients worldwide together with their families are still waiting for an effective treatment. We have recently initiated a re-evaluation of our knowledge of the molecular and cellular mechanisms underlying sporadic AD. Based on the existing literature, we have proposed a mechanistic explanation of how the late-onset form of the disease may evolve on the cellular level. Here, we expand this hypothesis by addressing the pathophysiological changes underlying the early and almost invariant appearance of the neurofibrillary tangles (NFTs), the only reliable correlate of the cognitive status, in distinct brain areas and their consistent "spread" along interconnected neurons as the disease advances. In this review we present and discuss novel evidence that the extracellular signaling protein Reelin, expressed along the olfactory and limbic pathways in the adult brain, might hold a key to understand the earliest steps of the disease, highlighting the olfactory pathway as the brain's Achilles heel involved in the initiation of the pathophysiology characteristic of late-onset AD.3

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“…12 Microglia cells, the brain cells which first sense this danger, are also able to defend the brain from it. 13 Under physiological conditions, the main function of these neural cells is to provide protective patrolling of the brain; however, in the presence of endotoxins such as LPS, they adopt the characteristics of brain macrophages in which Figure 1. Caspase-1 activation by inflammagenic nanoparticles.…”

mentioning

confidence: 99%

Caspase-1 Activity in Microglia Stimulated by Pro-Inflammagen Nanocrystals

Moquin¹,

Hutter

Choi

et al. 2013

ACS Nano

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These authors share equal first authorship.A n acute inflammatory response to an insult is largely a protective cellular response. An unopposed acute inflammatory process persists, leading to the characteristic chronic inflammation. Commonly, the sequel would be a deterioration of physiological function. An early intervention is therefore important to reduce or eliminate this undesirable consequence. To this end, several biomarkers of inflammation have been measured and tested; these biomarkers are mainly the products of enzymatic reactions. Caspase-1 is one of the most prominent of the enzymes involved in inflammation. 1 Inflammation can be induced by numerous exogenous agents, including airborne particles, biological aggregates, nanocrystals (quantum dots (QDs)) and lipopolysaccharides (LPS). 2 These inflammagens are recognized by macrophages and microglia and some of them bind to cell surface receptors such as Toll-like receptors (TLR). In particular, endotoxins, including LPS, bind TLR-4 and trigger receptor dimerization at the plasma membrane, which, in turn, activate signal transduction cascades to induce inflammation. 1 TLR-4 activation initiates both genomic and nongenomic inflammatory responses (i) by activating the transcription factor NF-κB, which translocates to the nucleus and induces the expression of pro-inflammatory cytokines (e.g., pro-interleukins), and (ii) by internalizing the bound endotoxin stimuli, fusing with lysosomes and triggering the formation of inflammasomes ( Figure 1A). Nod-like receptor protein-3 (NLRP-3) inflammasome 3À6 is one of the most wellstudied inflammasomes and contains the precursor pro-caspase-1, which is cleaved following inflammatory stimuli and releases its active form, caspase-1. 7 Caspase-1 is a cysteine protease which converts * Address correspondence to dusica.maysinger@mcgill.ca.Received for review January 14, 2013 and accepted October 9, 2013. Published online 10.1021/nn404473gABSTRACT Although caspase-1 is a key participant in inflammation, there is no sensitive assay to measure its enzymatic activity in real time in cells or animals. Here we describe a nanosensor for caspase-1 ratiometric measurements, consisting of a rhodamine-labeled, caspase-1 cleavable peptide linked to quantum dots (QDs). Microglia cells were stimulated by lipopolysaccharide (LPS) and by hybrid nanoparticles LPSÀQDs. These stimuli activated caspase-1 in microglia monolayers and in the mouse brain, while a selected caspase inhibitor markedly reduced it. LPSÀQDs entered into the lysosomal compartment and led to an enlargement of these cellular organelles in the exposed microglia. Both lysosomal swelling and mitochondrial impairment contributed to caspase-1 activation and to the consequent interleukin-1β release. The results from these studies highlight how the unique properties of QDs can be used to create versatile biotools in the study of inflammation in real time in vivo.

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Cytokines and olfactory bulb microglia in response to bacterial challenge in the compromised primary olfactory pathway

Cited by 56 publications

References 44 publications

Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion

Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion

Decisive role of Reelin signaling during early stages of Alzheimer’s disease

Caspase-1 Activity in Microglia Stimulated by Pro-Inflammagen Nanocrystals

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