Negative regulation of TLX by IL-1β correlates with an inhibition of adult hippocampal neural precursor cell proliferation

Ryan, Sinead M.; O’Keeffe, Gerard W.; O’Connor, Caitríona; Keeshan, Karen; Nolan, Yvonne M.

doi:10.1016/j.bbi.2013.03.005

Cited by 59 publications

(49 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, IL-1β enhances astrogliogenesis and inhibits neurogenesis via GSK-3β activation and TLX modulation in hippocampal NSCs [17] or p38 MAPK (mitogen-activated protein kinase) in mesencephalic NSCs [18]. The same effect is found in the SGZ, where a sustained expression of IL-1β produces a shift in cell lineage from neuronal to astroglial that requires the presence of IL-1R [10].…”

Section: Il-1β Signalling and Neurogenesismentioning

confidence: 76%

Neuroimmmune interactions of cannabinoids in neurogenesis: focus on interleukin-1β (IL-1β) signalling

Garcı́a-Ovejero

Arévalo-Martı́n

Navarro-Galve

et al. 2013

Biochemical Society Transactions

View full text Add to dashboard Cite

Neuroimmune networks and the brain endocannabinoid system contribute to the maintenance of neurogenesis. Activation of cannabinoid receptors suppresses chronic inflammatory responses through the attenuation of pro-inflammatory mediators. Moreover, the endocannabinoid system directs cell fate specification of NSCs (neural stem cells) in the CNS (central nervous system). The aim of our work is to understand better the relationship between the endocannabinoid and the IL-1β (interleukin-1β) associated signalling pathways and NSC biology, in order to develop therapeutical strategies on CNS diseases that may facilitate brain repair. NSCs express functional CB1 and CB2 cannabinoid receptors, DAGLα (diacylglycerol lipase α) and the NSC markers SOX-2 and nestin. We have investigated the role of CB1 and CB2 cannabinoid receptors in the control of NSC proliferation and in the release of immunomodulators [IL-1β and IL-1Ra (IL-1 receptor antagonist)] that control NSC fate decisions. Pharmacological blockade of CB1 and/or CB2 cannabinoid receptors abolish or decrease NSC proliferation, indicating a critical role for both CB1 and CB2 receptors in the proliferation of NSC via IL-1 signalling pathways. Thus the endocannabinoid system, which has neuroprotective and immunomodulatory actions mediated by IL-1 signalling cascades in the brain, could assist the process of proliferation and differentiation of embryonic or adult NSCs, and this may be of therapeutic interest in the emerging field of brain repair.

show abstract

Section: Il-1β Signalling and Neurogenesismentioning

confidence: 76%

Neuroimmmune interactions of cannabinoids in neurogenesis: focus on interleukin-1β (IL-1β) signalling

Garcı́a-Ovejero

Arévalo-Martı́n

Navarro-Galve

et al. 2013

Biochemical Society Transactions

View full text Add to dashboard Cite

show abstract

“…IL-1β also acts to repress TLX in differentiating new-born neurons, mature neurons, and astrocytes [81–83]. Recently, it has been demonstrated that this repression of TLX and hippocampal NPC proliferation is mediated through the interleukin-1 receptor type I [84]. …”

Section: Introductionmentioning

confidence: 99%

TLX: A master regulator for neural stem cell maintenance and neurogenesis

Islam¹,

Zhang²

2015

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

View full text Add to dashboard Cite

The orphan nuclear receptor TLX, also known as NR2E1, is an essential regulator of neural stem cell (NSC) self-renewal, maintenance, and neurogenesis. In vertebrates, TLX is specifically localized to the neurogenic regions of the forebrain and retina throughout development and adulthood. TLX regulates the expression of genes involved in multiple pathways, such as the cell cycle, DNA replication, and cell adhesion. These roles are primarily performed through the transcriptional repression or activation of downstream target genes. Emerging evidence suggests the misregulation of TLX might play a role in the onset and progression of human neurological disorders making this factor an ideal therapeutic target. Here, we review the current understanding of TLX function, expression, regulation, and activity significant to NSC maintenance, adult neurogenesis, and brain plasticity.

show abstract

“…Several studies indicate that IL-1β is antineurogenic (Koo and Duman, 2008;Ryan et al, 2013) by activation of the tumor suppressor p53 (Guadagno et al, 2015) or via adrenocortical activation (Goshen et al, 2008). Other findings suggest a proneurogenic effect of IL-1β (de la Mano et al, 2007;Xue et al, 2015).…”

mentioning

confidence: 99%

Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways

et al. 2016

View full text Add to dashboard Cite

Running title: EPA, but not DHA induces proliferation in NSCs Abbreviations: AA, Arachidonic acid, AEA, anandamide, DHA. Docosahexaenoic acid; EPA, eicosapentaenoic acid, 2-AG, 2-arachidonylglycerol 2 Title: Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways Emerging evidence suggests a complex interplay between the endocannabinoid system, omega-3 fatty acids and the immune system in the promotion of brain self-repair. However, it is unknown if all omega-3 fatty acids elicit similar effects on adult neurogenesis and if such effects are mediated or regulated by interactions with the endocannabinoid system. This study investigated the effects of DHA and EPA on neural stem cell (NSC) fate and the role of the endocannabinoid signalling pathways in these effects.EPA, but not DHA, significantly increased proliferation of NSCs compared to controls, an effect associated with enhanced levels of the endocannabinoid 2-arachidonylglycerol (2-AG) and p-p38 MAPK, effects attenuated by pre-treatment with CB1 (AM251) or CB2 (AM630) receptor antagonists. Furthermore, in NSCs derived from IL-1 deficient mice, EPA significantly decreased proliferation and p-p38 MAPK levels compared to controls, suggesting a key role for IL-1 signalling in the effects observed. Although DHA similarly increased 2-AG levels in wild-type NSCs, there was no concomitant increase in proliferation or p-p38 MAPK activity. In addition, in NSCs from IL-1 deficient mice, DHA significantly increased proliferation without effects on p-P38 MAPK, suggesting effects of DHA are mediated via alternative signalling pathways. These results provide crucial new insights into the divergent effects of EPA and DHA in regulating NSC proliferation and the pathways involved, and highlight the therapeutic potential of their interplay with endocannabinoid signalling in brain repair.

show abstract

Negative regulation of TLX by IL-1β correlates with an inhibition of adult hippocampal neural precursor cell proliferation

Cited by 59 publications

References 35 publications

Neuroimmmune interactions of cannabinoids in neurogenesis: focus on interleukin-1β (IL-1β) signalling

Neuroimmmune interactions of cannabinoids in neurogenesis: focus on interleukin-1β (IL-1β) signalling

TLX: A master regulator for neural stem cell maintenance and neurogenesis

Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways

Contact Info

Product

Resources

About