Alerted microglia and the sympathetic nervous system: A novel form of microglia in the development of hypertension

Kapoor, Komal; Bhandare, Amol M.; Farnham, Melissa M.J.; Pilowsky, Paul M.

doi:10.1016/j.resp.2015.11.015

Cited by 33 publications

(22 citation statements)

References 98 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the present study, we assessed microglial characteristics 24 h after the SH protocol. Therefore, it is possible that more pronounced morphological changes occurred in a time window before our evaluation (Kapoor et al 2016;Bhandare et al 2017). In fact, studies by Tadmouri et al (2014) using cluster differentiation 11 (CD11), a specific marker for activated microglia, showed that the number of activated microglia was increased in the NTS during the period between 6 and 24 h of exposure to SH and this increase was blunted by minocycline treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it is possible that more pronounced morphological changes occurred in a time window before our evaluation (Kapoor et al . ; Bhandare et al . ).…”

Section: Discussionmentioning

confidence: 99%

“…There is evidence that these cells have a high mobility and ability to change their morphology quickly (Cohen et al 2018). Previous studies showed that depending on the situation, microglia may acquire the 'alert microglia' phenotype, a state in which these cells are more activated than in their basal condition, but are not yet fully activated as in their amoeboid state; in this case, even if activated, these microglia cells may present a morphology quite similar to surveillance microglia (Hanisch & Kettenmann, 2007;Kettenmann et al 2011;Kapoor et al 2016).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Enhancement of excitatory transmission in NTS neurons projecting to ventral medulla of rats exposed to sustained hypoxia is blunted by minocycline

Lima‐Silveira

Accorsi‐Mendonça

Bonagamba

et al. 2019

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

Key points Rats subjected to sustained hypoxia (SH) present increases in arterial pressure (AP) and in glutamatergic transmission in the nucleus tractus solitarius (NTS) neurons sending projections to ventrolateral medulla (VLM). Treatment with minocycline, a microglial inhibitor, attenuated the increase in AP in response to SH. The increase in the amplitude of glutamatergic postsynaptic currents in the NTS‐VLM neurons, induced by postsynaptic mechanisms, was blunted by minocycline treatment. The number of microglial cells was increased in the NTS of vehicle‐treated SH rats but not in the NTS of minocycline‐treated rats. The data show that microglial recruitment/proliferation induced by SH is associated with the enhancement of excitatory neurotransmission in NTS‐VLM neurons, which may contribute to the observed increase in AP. Abstract Short‐term sustained hypoxia (SH) produces significant autonomic and respiratory adjustments and triggers activation of microglia, the resident immune cells in the brain. SH also enhances glutamatergic neurotransmission in the NTS. Here we evaluated the role of microglial activation induced by SH on the cardiovascular changes and mainly on glutamatergic neurotransmission in NTS neurons sending projections to the ventrolateral medulla (NTS‐VLM), using a microglia inhibitor (minocycline). Direct measurement of arterial pressure (AP) in freely moving rats showed that SH (24 h, fraction of inspired oxygen (FI,O2) 0.1) in vehicle and minocycline (30 mg/kg i.p. for 3 days)‐treated groups produced a significant increase in AP in relation to control groups under normoxic conditions, but this increase was significantly lower in minocycline‐treated rats. Whole‐cell patch‐clamp recordings revealed that the active properties of the membrane were comparable among the groups. Nevertheless, the amplitudes of glutamatergic postsynaptic currents, evoked by tractus solitarius stimulation, were increased in NTS‐VLM neurons of SH rats. Changes in asynchronous glutamatergic currents indicated that the observed increase in amplitude was due to postsynaptic mechanisms. These changes were blunted in the SH group previously treated with minocycline. Using immunofluorescence, we found that the number of microglial cells was increased in the NTS of vehicle‐treated SH rats but not in the NTS neurons of minocycline‐treated rats. Our data support the concept that microglial activation induced by SH is associated with the enhancement of excitatory neurotransmission in NTS‐VLM neurons, which may contribute to the increase in AP observed in this experimental model.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Therefore, it is possible that more pronounced morphological changes occurred in a time window before our evaluation (Kapoor et al . ; Bhandare et al . ).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Enhancement of excitatory transmission in NTS neurons projecting to ventral medulla of rats exposed to sustained hypoxia is blunted by minocycline

Lima‐Silveira

Accorsi‐Mendonça

Bonagamba

et al. 2019

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…They respond to all types of pathological stimulus, including seizures, through activation, and adoption of either a 'pro-inflammatory M1' or 'antiinflammatory M2' phenotype (Li et al, 2007;Lai and Todd, 2008;Loane and Byrnes, 2010;Kapoor et al, 2016a). Epileptic seizures cause extensive microglial activation in patients (Beach et al, 1995), and in animal models (Drage et al, 2002), but there is a considerable controversy surrounding the pro- (Shapiro et al, 2008) or antiinflammatory (Mirrione et al, 2010;Eyo et al, 2014) role of microglia during and following a seizure.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of microglial activation with minocycline at the intrathecal level attenuates sympathoexcitatory and proarrhythmogenic changes in rats with chronic temporal lobe epilepsy

et al. 2017

Self Cite

View full text Add to dashboard Cite

(2017) Inhibition of microglial activation with minocycline at the intrathecal level attenuates sympathoexcitatory and proarrhythmogenic changes in rats with chronic temporal lobe epilepsy. Neuroscience, 350 . pp. 23-38 Permanent WRAP URL: http://wrap.warwick.ac.uk/87504 Copyright and reuse:The Warwick Research Archive Portal (WRAP) makes this work by researchers of the University of Warwick available open access under the following conditions. Copyright © and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable the material made available in WRAP has been checked for eligibility before being made available.Copies of full items can be used for personal research or study, educational, or not-for-profit purposes without prior permission or charge. Provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. A note on versions:The version presented here may differ from the published version or, version of record, if you wish to cite this item you are advised to consult the publisher's version. Please see the 'permanent WRAP URL' above for details on accessing the published version and note that access may require a subscription. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Abstract:The incidence of sudden unexpected death in epilepsy ( SE and control rats. We did not notice changes in microglial morphology or changes in a number of M2 phenotype in epileptic nor control rats in the vicinity of RVLM neurons. Our findings establish that microglial activation, and not PACAP, at the IML accounts for higher SNA and proarrhythmogenic changes during chronic epilepsy in rats. This is the first experimental evidence to support a neurotoxic effect of microglia during chronic epilepsy, in contrast to their neuroprotective action during acute seizures.

show abstract

“…; Kapoor et al . ). TNF‐α and IL‐1β signalling activates NF‐κB, promoting cytokine synthesis and AT1 upregulation (Szczepanska‐Sadowska et al .…”

Section: Introductionmentioning

confidence: 97%

Neuroinflammation in heart failure: new insights for an old disease

Díaz

Toledo

Andrade

et al. 2019

The Journal of Physiology

View full text Add to dashboard Cite

Heart failure (HF) is a complex clinical syndrome affecting roughly 26 million people worldwide. Increased sympathetic drive is a hallmark of HF and is associated with disease progression and higher mortality risk. Several mechanisms contribute to enhanced sympathetic activity in HF, but these pathways are still incompletely understood. Previous work suggests that inflammation and activation of the renin-angiotensin system (RAS) increases sympathetic drive. Importantly, chronic inflammation in several brain regions is commonly observed in aged populations, and a growing body of evidence suggests neuroinflammation plays a crucial role in HF. In animal models of HF, central inhibition of RAS and pro-inflammatory cytokines normalizes Hugo S. Díaz H. S. Díaz and others J Physiol 598.1 sympathetic drive and improves cardiac function. The precise molecular and cellular mechanisms that lead to neuroinflammation and its effect on HF progression remain undetermined. This review summarizes the most recent advances in the field of neuroinflammation and autonomic control in HF. In addition, it focuses on cellular and molecular mediators of neuroinflammation in HF and in particular on brain regions involved in sympathetic control. Finally, we will comment on what is known about neuroinflammation in the context of preserved vs. reduced ejection fraction HF. Abstract figure legendIntegrative physiology of heart failure progression: Heart failure (HF) is characterized by chronic inflammation, renin-angiotensin system (RAS) overactivity, sympathoexcitation and cardiac dysfunction. Sympathoexcitation and RAS activation occur early in HF progression as a compensatory response to haemodynamic challenges. Chronic activation of these compensatory mechanisms becomes maladaptive and has toxic effects on cardiac muscle leading to electrophysiological abnormalities and initiation of fibrotic processes. RAS activation also enhances chemoreflex sensitivity (further exacerbating sympathetic activation) and promotes diffuse inflammation. Both systemic and brain RAS and inflammation feed back to exacerbate sympathoexcitation, generating a vicious cycle that contributes to further cardiac dysfunction.

show abstract

Alerted microglia and the sympathetic nervous system: A novel form of microglia in the development of hypertension

Cited by 33 publications

References 98 publications

Enhancement of excitatory transmission in NTS neurons projecting to ventral medulla of rats exposed to sustained hypoxia is blunted by minocycline

Enhancement of excitatory transmission in NTS neurons projecting to ventral medulla of rats exposed to sustained hypoxia is blunted by minocycline

Inhibition of microglial activation with minocycline at the intrathecal level attenuates sympathoexcitatory and proarrhythmogenic changes in rats with chronic temporal lobe epilepsy

Neuroinflammation in heart failure: new insights for an old disease

Contact Info

Product

Resources

About