Innate immune responses regulate morphogenesis and degeneration: roles of Toll-like receptors and Sarm1 in neurons

Liu, Hsin‐Yu; Chen, Chiung-Ya; Hsueh, Yi‐Ping

doi:10.1007/s12264-014-1445-5

Cited by 43 publications

(38 citation statements)

References 60 publications

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“…) particularly as recent studies suggest that neurons may possess the necessary components to sense bacterial infection, thus acting as a trigger for innate immunity signalling (Liu et al . ). Indeed, LPS inhibition of AMPK expression in vivo is not limited to adult tissue as a very recent paper described the same phenomenon in weaned piglets (Kang et al .…”

Section: Discussionmentioning

confidence: 97%

A dual role for AMP‐activated protein kinase (AMPK) during neonatal hypoxic–ischaemic brain injury in mice

Rousset

Leiper

Kichev

et al. 2015

Journal of Neurochemistry

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Perinatal hypoxic-ischaemic encephalopathy (HIE) occurs in 1-2 in every 1000 term infants and the devastating consequences range from cerebral palsy, epilepsy and neurological deficit to death. Cellular damage post insult occurs after a delay and is mediated by a secondary neural energy failure. AMP-activated protein kinase (AMPK) is a sensor of cellular stress resulting from ATP depletion and/or calcium dysregulation, hallmarks of the neuronal cell death observed after HIE. AMPK activation has been implicated in the models of adult ischaemic injury but, as yet, there have been no studies defining its role in neonatal asphyxia. Here, we find that in an in vivo model of neonatal hypoxia-ischaemic and in oxygen/glucose deprivation in neurons, there is pathological activation of the calcium/calmodulin-dependent protein kinase kinase b (CaMKKb)-AMPKa1 signalling pathway. Pharmacological inhibition of AMPK during the insult promotes neuronal survival but, conversely, inhibiting AMPK activity prior to the insult sensitizes neurons, exacerbating cell death. Our data have pathological relevance for neonatal HIE as prior sensitization such as exposure to bacterial infection (reported to reduce AMPK activity) produces a significant increase in injury.

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Section: Discussionmentioning

confidence: 97%

A dual role for AMP‐activated protein kinase (AMPK) during neonatal hypoxic–ischaemic brain injury in mice

Rousset

Leiper

Kichev

et al. 2015

Journal of Neurochemistry

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“…Regardless, neuronal expressions of TLRs have been demonstrated by multiple studies (Liu et al, 2014). Expressions of TLR1, TLR2, TLR3, and TLR4 have been detected in human NT2-N neuronal cell line (Lafon et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Recent study showed that expression and activation of neuronal TLR2 and 4 contributed to neurodegeneration by ischemic stroke (Tang et al, 2007). Studies have also suggested the roles of TLRs, such as TLR3, TLR7, and TLR8, in neural morphogenesis (Liu et al, 2014). Activation of TLR3 induces growth-cone collapse and inhibits neurite outgrowth in cultured dorsal root ganglion, cortical, and hippocampal neurons (Cameron et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Antagonizing Neuronal Toll-like Receptor 2 Prevents Synucleinopathy by Activating Autophagy

et al. 2015

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SUMMARY Impaired autophagy has been implicated in many neurodegenerative diseases, such as Parkinson's disease (PD), and might be responsible for deposition of aggregated proteins in neurons. However, little is known how neuronal autophagy and clearance of aggregated proteins are regulated. Here, we show a role for Toll-like receptor 2 (TLR2), a pathogen-recognizing receptor in innate immunity, in regulation of neuronal autophagy and clearance of α-synuclein, a protein aggregated in synucleinopathies, including PD. Activation of TLR2 resulted in accumulation of α-synuclein aggregates in neurons as a result of inhibition of autophagic activity through regulation of the AKT/mTOR pathway. In contrast, inactivation of TLR2 resulted in autophagy activation and increased clearance of neuronal α-synuclein, hence reduced neurodegeneration, in transgenic mice and in in vitro models. These results uncover novel roles of TLR2 in regulating neuronal autophagy, and the TLR2 pathway may be targeted for the autophagy activation strategies in treating neurodegenerative disorders.

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“…Blood-borne and neural routes of communication between the peripheral and central nervous systems have been well-defined (Dinarello et al, 1988; Ericsson et al, 1994; Maier, 2003) and systemic immune challenge dramatically alters neural activity (Barrientos et al, 2015; Chapman et al, 2010; Maier and Watkins, 1998) and ablates the production of new highly excitable hippocampal granule neurons (Chen et al, 2011; Ekdahl et al, 2003; Ekdahl et al, 2009; Monje et al, 2002; Monje et al, 2003; Ormerod et al, 2013). Systemic inflammation can stimulate the de novo synthesis of brain parenchymal cytokines primarily by microglia (Layé et al, 1996; Nguyen et al, 1998; Van Dam et al, 1995) but also by other CNS cells (Liu et al, 2014; Vincent et al, 1998). In turn, neuroinflammation can impact the production of systemic cytokines (Campbell et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Some hormone, cytokine and chemokine levels that change across lifespan vary by cognitive status in male Fischer 344 rats

Scheinert

Asokan

Rani

et al. 2015

Brain, Behavior, and Immunity

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We trained and tested young (6–8 mo; n = 13), middle-aged (12–14 mo; n = 41), and aged (22–24 mo; n = 24) male Fischer 344 rats in a rapid acquisition water maze task and then quantified 27 stress hormones, cytokines and chemokines in their serum, hippocampi and frontal cortices using bead assay kits and xMAP technology. Middle-aged and aged rats learned the location of the hidden platform over training trials more slowly than their young counterparts. After training, young rats outperformed middle-aged and aged rats on both immediate and 24h retention probe trials and about half of the middle-aged and aged (aging) rats exhibited impaired performances when tested on the retention probe trial 24h later. The concentrations of many serum, hippocampal and cortical analytes changed with age often in networks that may represent age-sensitive signaling pathways and the concentrations of some of these analytes correlated with water maze learning and/or memory scores. Serum GRO/KC and RANTES levels, hippocampal GM-CSF levels and cortical IL-9 and RANTES levels were significantly higher in rats categorized as memory-impaired versus elite agers based upon their 24h probe trial performances. Our data add to the emerging picture of how age-related changes in immune and neuroimmune system signaling impacts cognition.

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Innate immune responses regulate morphogenesis and degeneration: roles of Toll-like receptors and Sarm1 in neurons

Cited by 43 publications

References 60 publications

A dual role for AMP‐activated protein kinase (AMPK) during neonatal hypoxic–ischaemic brain injury in mice

A dual role for AMP‐activated protein kinase (AMPK) during neonatal hypoxic–ischaemic brain injury in mice

Antagonizing Neuronal Toll-like Receptor 2 Prevents Synucleinopathy by Activating Autophagy

Some hormone, cytokine and chemokine levels that change across lifespan vary by cognitive status in male Fischer 344 rats

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