Tumour necrosis factor-α impairs neuronal differentiation but not proliferation of hippocampal neural precursor cells: Role of Hes1

Keohane, Aoife; Ryan, Sinead M.; Maloney, Eimer; Sullivan, Aideen M.; Nolan, Yvonne M.

doi:10.1016/j.mcn.2009.10.003

Cited by 98 publications

(85 citation statements)

References 37 publications

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“…In the present study, we confirmed that the brain inflammatory response, as illustrated by microglial activation and TNF-α protein expression, resulted in decreased number of newly born neurons. This observation is in line with previous studies demonstrating the deleterious effect of TNF-α on the survival of neural precursor cells (Ekdahl et al, 2003; Iosif et al, 2006; Keohane et al, 2010; Ekdahl, 2012). More interestingly, we demonstrated for the first time that an HRT regimen containing both 17β-estradiol and progesterone, not only blunted brain inflammation but it also dampened brain inflammation-induced reduction in newly born neurons.…”

Section: Discussionsupporting

confidence: 93%

TLR4-mediated brain inflammation halts neurogenesis: impact of hormonal replacement therapy

Mouihate

2014

Front. Cell. Neurosci.

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Experimental and epidemiological data show that the severity and the duration of brain inflammation are attenuated in females compared to males. This attenuated brain inflammation is ascribed to 17β-estradiol. However, several studies suggest that 17β-estradiol is also endowed with proinflammatory properties. The aim of the present study is to assess the effect of hormonal replacement therapies on lipopolysaccharide (LPS)-induced brain inflammation and its consequent effect on newly born neurons. Bilaterally ovariectomized rats received intrastriatal injection of LPS (250 ng/μl) and were subsequently given daily subcutaneous injections of either vehicle, 17β-estradiol (25 μg/kg) or 17β-estradiol and progesterone (5 mg/kg). Microglial activation and newly born neurons in the rostral migratory stream were monitored using double immunofluorescence. Nuclear factor κB (NFκB) signaling pathway and its target inflammatory proteins were assessed by either western blot [cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6)] or enzyme-linked immunosorbent assay [tumor necrosis factor-α (TNF-α)]. LPS-induced activation of microglia, promoted NFκB signaling pathway and enhanced the production of proinflammatory proteins (TNF-α and COX-2). These proinflammatory responses were not attenuated by 17β-estradiol injection. Supplementation of 17β-estradiol with progesterone significantly dampened these proinflammatory processes. Interestingly, LPS-induced brain inflammation dampened the number of newly born neurons in the rostral migratory stream. Administration of combined 17β-estradiol and progesterone resulted in a significantly higher number of newly born neurons when compared to those seen in rats given either vehicle or 17β-estradiol alone. These data strongly suggest that combined 17β-estradiol and progesterone, and not 17β-estradiol alone, rescues neurogenesis from the deleterious effect of brain inflammation likely via the inhibition of the signaling pathways leading to the activation of proinflammatory genes.

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Section: Discussionsupporting

confidence: 93%

TLR4-mediated brain inflammation halts neurogenesis: impact of hormonal replacement therapy

Mouihate

2014

Front. Cell. Neurosci.

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“…Furthermore, TNF-α knockout mice exhibit altered hippocampal development whereby dentate gyrus maturation is quicker and dendritic tree arborization of the CA1 and CA3 sub-regions are significantly retarded, which may be due to the ability of TNF-α to modulate growth factors that influence pyramidal cell migration of the hippocampus (Golan et al 2004). Interestingly, astrocytes may promote these morphological alterations given that astrocytic GFAP-deficient mice harbor neurons comprised of dense and elongated neurites, possibly speaking to a role for TNF-α in astrocyte differentiation as mentioned previously (Menet et al 2000;Keohane et al 2010).…”

Section: Developmentmentioning

confidence: 77%

“…Keohane et al reported embryonic neural progenitor cell (NPC) proliferation is unaffected by TNF-α, while cell lineage fate differentiation is anti-neurogenically skewed resulting in a loss of embryonic neurons and an elevation of newly born astrocytes ( Fig. 3) (Keohane et al 2010). The authors posited that TNF-α differentially regulates cell proliferation and differentiation and these differences may be due to upregulated HES1 gene expression, an anti-neurogenic factor, and increased TNF-receptor expression subsequent to the addition of TNF-α on differentiating NPCs.…”

Section: Developmentmentioning

confidence: 99%

Tumor Necrosis Factor-alpha and the Roles it Plays in Homeostatic and Degenerative Processes Within the Central Nervous System

Montgomery

Bowers

2011

J Neuroimmune Pharmacol

294

177

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Tumor Necrosis Factor-alpha (TNF-α) is a prototypic pro-inflammatory cytokine involved in the innate immune response. TNF-α ligation and downstream signaling with one of its cognate receptors, TNF-RI or TNF-RII, modulates fundamental processes in the brain including synapse formation and regulation, neurogenesis, regeneration, and general maintenance of the central nervous system (CNS). During states of chronic neuroinflammation, extensive experimental evidence implicates TNF-α as a key mediator in disease progression, gliosis, demyelination, inflammation, blood-brain-barrier deterioration, and cell death. This review explores the complex roles of TNF-α in the CNS under normal physiologic conditions and during neurodegeneration. We focus our discussion on Multiple Sclerosis, Parkinson's disease, and Alzheimer's disease, relaying the outcomes of preclinical and clinical testing of TNF-α directed therapeutic strategies, and arguing that despite the wealth of functions attributed to this central cytokine, surprisingly little is known about the cell type- and stage-specific roles of TNF-α in these debilitating disorders.

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“…TNF-α is also one of the major pro-inflammatory cytokines inhibiting neurogenesis (Keohane et al, 2010;Monje et al, 2003). The two receptors for TNF-α, tumor necrosis factor receptor (TNFR)-1 and TNFR-2, mediate the actions of TNF-α in neurogenesis.…”

Section: Pro-inflammatory Cytokines and Neurogenesismentioning

confidence: 99%

“…Decreased number of newly generated neuronsMonje et al (2003) Decreased proliferation and differentiationKeohane et al (2010) Decreased differentiation and increased proportion of astrocytes…”

mentioning

confidence: 99%

The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression

Kim

Lee

Myint

et al. 2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

475

276

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Cytokines are pleiotropic molecules with important roles in inflammatory responses. Pro-inflammatory cytokines and neuroinflammation are important not only in inflammatory responses but also in neurogenesis and neuroprotection. Sustained stress and the subsequent release of pro-inflammatory cytokines lead to chronic neuroinflammation, which contributes to depression. Hippocampal glucocorticoid receptors (GRs) and the associated hypothalamus-pituitary-adrenal (HPA) axis have close interactions with pro-inflammatory cytokines and neuroinflammation. Elevated pro-inflammatory cytokine levels and GR functional resistance are among the most widely investigated factors in the pathophysiology of depression. These two major components create a vicious cycle. In brief, chronic neuroinflammation inhibits GR function, which in turn exacerbates pro-inflammatory cytokine activity and aggravates chronic neuroinflammation. On the other hand, neuroinflammation causes an imbalance between oxidative stress and the anti-oxidant system, which is also associated with depression. Although current evidence strongly suggests that cytokines and GRs have important roles in depression, they are essential components of a whole system of inflammatory and endocrine interactions, rather than playing independent parts. Despite the evidence that a dysfunctional immune and endocrine system contributes to the pathophysiology of depression, much research remains to be undertaken to clarify the cause and effect relationship between depression and neuroinflammation.

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Tumour necrosis factor-α impairs neuronal differentiation but not proliferation of hippocampal neural precursor cells: Role of Hes1

Cited by 98 publications

References 37 publications

TLR4-mediated brain inflammation halts neurogenesis: impact of hormonal replacement therapy

TLR4-mediated brain inflammation halts neurogenesis: impact of hormonal replacement therapy

Tumor Necrosis Factor-alpha and the Roles it Plays in Homeostatic and Degenerative Processes Within the Central Nervous System

The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression

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