Neuroinflammation and neurosteroidogenesis: Reciprocal modulation during injury to the adult zebra finch brain

Pedersen, Alyssa L.; Brownrout, Jenna L; Saldanha, Colin J.

doi:10.1016/j.physbeh.2017.10.013

Cited by 23 publications

(34 citation statements)

References 86 publications

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“…Hence, our findings may help to clarify the mechanisms underlying the neuroprotective action of oestrogens on cognitive functions. Several experimental studies conducted in animal and in vitro models have demonstrated that the anti‐inflammatory action of oestrogens is exerted via an inhibition of the inflammatory response by microglia and astroglia, reducing NF‐κB p65 activity and the expression of pro‐inflammatory cytokines . Recent findings suggested a novel E 2 ‐mediated neuroprotective effect via regulation of microglia activation and promotion of the M2 anti‐inflammatory phenotype in the brain of young adult ovariectomised rats .…”

Section: Discussionmentioning

confidence: 99%

“…Recent findings suggested a novel E 2 ‐mediated neuroprotective effect via regulation of microglia activation and promotion of the M2 anti‐inflammatory phenotype in the brain of young adult ovariectomised rats . Moreover, there is evidence to suggest that neuroinflammation is capable of inducing glial aromatase expression in brain injury models, thus supporting the involvement of E 2 in modulating the brain response to pro‐inflammatory mechanisms . However, less is known about direct, non‐glia‐mediated, anti‐inflammatory effects of oestrogens on neurones.…”

Section: Discussionmentioning

confidence: 99%

“…To date, knowledge of the mechanisms underlying the action of oestrogen in the brain has mainly derived from studies conducted in ani- of pro-inflammatory cytokines. 32,33,44 Recent findings suggested a novel E 2 -mediated neuroprotective effect via regulation of microglia activation and promotion of the M2 anti-inflammatory phenotype in the brain of young adult ovariectomised rats. 45 Moreover, there is evidence to suggest that neuroinflammation is capable of inducing glial aromatase expression in brain injury models, thus supporting the involvement of E 2 in modulating the brain response to proinflammatory mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…Reducing circulating levels of oestrogen could therefore aggravate the neuroinflammatory response that normally occurs with ageing . Indeed, E 2 controls neuroinflammation via a modulatory action on the activity of glial cells involved in the inflammatory response, as detected in animal models . However, it is unclear whether E 2 can have direct, anti‐inflammatory effects on cholinergic neurones, in particular in the NBM.…”

Section: Introductionmentioning

confidence: 99%

“…31 Indeed, E 2 controls neuroinflammation via a modulatory action on the activity of glial cells involved in the inflammatory response, as detected in animal models. 32,33 However, it is unclear whether E 2 can have direct, anti-inflammatory effects on cholinergic neurones, in particular in the NBM. In this context, we recently demonstrated that a primary culture of cholinergic neurones isolated from the human foetal NBM (hfNBM cells) expresses all types of oestrogen receptors that may be differently involved in mediating oestrogenic action on growth, differentiation and maintenance of the cholinergic phenotype.…”

Section: Introductionmentioning

confidence: 99%

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The G protein‐coupled oestrogen receptor, GPER1, mediates direct anti‐inflammatory effects of oestrogens in human cholinergic neurones from the nucleus basalis of Meynert

Sarchielli

Guarnieri

Idrizaj

et al. 2020

J Neuroendocrinology

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It has been well established, particularly in animal models, that oestrogens exert neuroprotective effects in brain areas linked to cognitive processes. A key protective role could reside in the capacity of oestrogen to modulate the inflammatory response. However, the direct neuroprotective actions of oestrogens on neurones are complex and remain to be fully clarified. In the present study, we took advantage of a previously characterised primary culture of human cholinergic neurones (hfNBM) from the foetal nucleus basalis of Meynert, which is known to regulate hippocampal and neocortical learning and memory circuits, aiming to investigate the direct effects of oestrogens under inflammatory conditions. Exposure of cells to tumour necrosis factor (TNF)α (10 ng mL‐1) determined the activation of an inflammatory response, as demonstrated by nuclear factor‐kappa B p65 nuclear translocation and cyclooxygenase‐2 mRNA expression. These effects were inhibited by treatment with either 17β‐oestradiol (E2) (10 nmol L‐1) or G1 (100 nmol L‐1), the selective agonist of the G protein‐coupled oestrogen receptor (GPER1). Interestingly, the GPER1 antagonist G15 abolished the effects of E2 in TNFα‐treated cells, whereas the ERα/ERβ inhibitor tamoxifen did not. Electrophysiological measurements in hfNBMs revealed a depolarising effect caused by E2 that was specifically blocked by tamoxifen and not by G15. Conversely, G1 specifically hyperpolarised the cell membrane and also increased both inward and outward currents elicited by a depolarising stimulus, suggesting a modulatory action on hfNBM excitability by GPER1 activation. Interestingly, pretreating cells with TNFα completely blocked the effects of G1 on membrane properties and also significantly reduced GPER1 mRNA expression. In addition, we found a peculiar subcellular localisation of GPER1 to focal adhesion sites that implicates new possible mechanisms of action of GPER1 in the neuronal perception of mechanical stimuli. The results obtained in the present study indicate a modulatory functional role of GPER1 with respect to mediating the oestrogen neuroprotective effect against inflammation in brain cholinergic neurones and, accordingly, may help to identify protective strategies for preventing cognitive impairments.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%