Chronic mild hypoxia promotes hippocampal neurogenesis involving Notch1 signaling in epileptic rats

Sun, Can Lan; Fu, Junfen; Qu, Zhenzhen; Li, Dongxiao; Si, Peipei; Qiao, Qi; Zhang, Wenlin; Xue, Yan; Zhen, Junli; Wang, Weiping

doi:10.1016/j.brainres.2019.02.011

Cited by 21 publications

(21 citation statements)

References 44 publications

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“…α-ketoglutarate (αKG, also known as 2-oxoglutarate) is a TCA cycle intermediate that can be converted to the neurotransmitter glutamate [146], thus firmly linking energy metabolism and oxygen sensing to neuronal function and potentially neurogenesis [147]. Recently, chronic mild hypoxia has been linked to adult neurogenesis in the hippocampus [148], while the deletion of HIF1α in mouse neural cells led to hydrocephaly, reduced number of NSCs and impaired spatial memory [149]. Along this line, work on stroke patients suggests that ischemia leads to the proliferation of NSCs in the SVZ and SGZ of the dentate gyrus, migration towards the lesion, and integration into the damaged area [52,53].…”

Section: Redox State and Rosmentioning

confidence: 99%

Metabolic regulation of neurodifferentiation in the adult brain

Maffezzini

Calvo‐Garrido

Wredenberg

et al. 2020

Cell. Mol. Life Sci.

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Understanding the mechanisms behind neurodifferentiation in adults will be an important milestone in our quest to identify treatment strategies for cognitive disorders observed during our natural ageing or disease. It is now clear that the maturation of neural stem cells to neurones, fully integrated into neuronal circuits requires a complete remodelling of cellular metabolism, including switching the cellular energy source. Mitochondria are central for this transition and are increasingly seen as the regulatory hub in defining neural stem cell fate and neurodevelopment. This review explores our current knowledge of metabolism during adult neurodifferentiation.

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Section: Redox State and Rosmentioning

confidence: 99%

Metabolic regulation of neurodifferentiation in the adult brain

Maffezzini

Calvo‐Garrido

Wredenberg

et al. 2020

Cell. Mol. Life Sci.

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“…Overall, HH exposure at 25000ft elicits detrimental effect on progenitor, proliferative, immature neurons in DG. In other hypoxia-related studies like intermittent hypoxia witnessed contradictory contributions towards the generation of new-born neurons in DG, whereas ischemia majorly suppresses adult neurogenesis [55,56,57]. Whereas, there is a study where number of Ki-67 and DCX+ hosphor cells elevated upon high altitude exposure in rats at 3450m via elevation in VEGF signaling [58].…”

Section: Discussionmentioning

confidence: 99%

COX-1/EP1R Inhibition Ameliorate Deficits in Adult Neurogenesis and Social Interaction via Alleviating NLRP3/ IL-1β Activation During Hypobaric Hypoxia

Chauhan¹,

Kumar²,

Roy³

et al. 2020

Preprint

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BackgroundLow oxygen environments like hypobaric hypoxia (HH) are common nodes to various diseases: characterized by neuroinflammation, which is detrimental to the structural and functional aspects of hippocampal circuitry. Various hypoxic conditions also lead to elevation of NLRP3 mediated neuroinflammation that may contribute to cognitive deficits. Components of neurogenic niches like microglia and astrocyte are largely affected by neuroinflammation; however, a systematic investigation of the impact of NLRP3 mediated neuroinflammation on components of neurogenic niche during hypoxia (HH) remains elusive. MethodsIn this study, we simulated cerebral hypoxia via decreasing partial pressure of oxygen(HH). The effect of hypobaric hypoxic (1, 3 and 7 day at 25000 ft) on social memory, anxiety, adult neurogenesis change in the inflammatory milieu in DG was explored in detail. We explored the efficacy of COX-1 inhibitor (Valery salicylate, 5mg/kg/day,i.p), and EP1R antagonist (SC19220, 1mg/kg/day,i.p) on NLRP3 mediated neuroinflammation and associated maladies during HH. ResultsWe observed that HH exposure induced alteration in social and anxiety-like behavior post 7 day exposure along with perturbation in levels of BDNF, Serotonin and adult neurogenesis in the DG right from day 1. Moreover, significant elevated NLRP3, caspase-1, and IL-1β levels are observed during HH from day 1. Concomitantly, a notable increase in the COX-1/EP1 pathway in both activated microglia and astrocyte in DG was evident after 3HH exposure. Pharmacological COX-1 inhibitor and EP1 antagonist counteract the detrimental effects of HH exposure on social memory, adult neurogenesis, and NLRP3 inflammasome induction. ConclusionsThus, our data showed induction of the COX-1/EP1 pathway in glial cells is detrimental to adult neurogenesis and social memory, raising possibility that the COX-1/EP1 pathway as a plausible target for inflammasome related neurogenesis impairment.

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“…In fact, aHGG are mainly located in hemispheres, whereas pHGG are frequently located in midline brainstem and thalamic structures. As already mentioned, O 2 tensions and hypoxic niches are not directly located in those brain areas [21,23,34,35,43]. Nevertheless, both aHGG and pHGG invade the SVZ at the end of their evolution with differences in the invasive process under the pressure of hypoxic regions and gene deregulations [36].…”

Section: Comparison With Adult High-grade Glioma (Ahgg) Hypoxiamentioning

confidence: 97%

“…Hippocampus and cerebellum neurons seem very sensitive and hypoxia-intolerant [26], whereas neural stem-cells require hypoxic niches to remain in an undifferentiated state and maintain their pluripotency [34]. The physiological hypoxic niches are notably located in the sub-ventricular zone (SVZ) along the lateral walls of the lateral ventricles, the major site of post-natal continuous neurogenesis [23,34,35]. Controversial studies have investigated this SVZ niche as a region originating glioma stem cells [36,37].…”

Section: Role Of Brain Physiological Hypoxia Location or Brain Physiomentioning

confidence: 99%

Hypoxia Inducible Factors’ Signaling in Pediatric High-Grade Gliomas: Role, Modelization and Innovative Targeted Approaches

Fuchs

Pierrevelcin

Messé

et al. 2020

Cancers

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The brain tumor microenvironment has recently become a major challenge in all pediatric cancers, but especially in brain tumors like high-grade gliomas. Hypoxia is one of the extrinsic tumor features that interacts with tumor cells, but also with the blood-brain barrier and all normal brain cells. It is the result of a dramatic proliferation and expansion of tumor cells that deprive the tissues of oxygen inflow. However, cancer cells, especially tumor stem cells, can endure extreme hypoxic conditions by rescheduling various genes' expression involved in cell proliferation, metabolism and angiogenesis and thus, promote tumor expansion, therapeutic resistance and metabolic adaptation. This cellular adaptation implies Hypoxia-Inducible Factors (HIF), namely HIF-1α and HIF-2α. In pediatric high-grade gliomas (pHGGs), several questions remained open on hypoxia-specific role in normal brain during gliomagenesis and pHGG progression, as well how to model it in preclinical studies and how it might be counteracted with targeted therapies. Therefore, this review aims to gather various data about this key extrinsic tumor factor in pHGGs.

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Chronic mild hypoxia promotes hippocampal neurogenesis involving Notch1 signaling in epileptic rats

Cited by 21 publications

References 44 publications

Metabolic regulation of neurodifferentiation in the adult brain

Metabolic regulation of neurodifferentiation in the adult brain

COX-1/EP1R Inhibition Ameliorate Deficits in Adult Neurogenesis and Social Interaction via Alleviating NLRP3/ IL-1β Activation During Hypobaric Hypoxia

Hypoxia Inducible Factors’ Signaling in Pediatric High-Grade Gliomas: Role, Modelization and Innovative Targeted Approaches

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Chronic mild hypoxia promotes hippocampal neurogenesis involving Notch1 signaling in epileptic rats

Cited by 21 publications

References 44 publications

Metabolic regulation of neurodifferentiation in the adult brain

Metabolic regulation of neurodifferentiation in the adult brain

COX-1/EP1R&nbsp;Inhibition Ameliorate Deficits in Adult Neurogenesis and Social Interaction via Alleviating NLRP3/ IL-1β Activation During Hypobaric Hypoxia

Hypoxia Inducible Factors’ Signaling in Pediatric High-Grade Gliomas: Role, Modelization and Innovative Targeted Approaches

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COX-1/EP1R Inhibition Ameliorate Deficits in Adult Neurogenesis and Social Interaction via Alleviating NLRP3/ IL-1β Activation During Hypobaric Hypoxia