Crosstalk between insulin-like growth factor-1 and angiotensin-II in dopaminergic neurons and glial cells: role in neuroinflammation and aging

Rodríguez‐Pérez, Ana I.; Borrajo, Ana; Díaz-Ruiz, Carmen; Garrido‐Gil, Pablo; Labandeira‐Garcia, Jose L.

doi:10.18632/oncotarget.9174

Cited by 56 publications

(51 citation statements)

References 66 publications

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“…Consistent with this, AT1 receptor antagonists reduce proinflammatory microglia activation and promote immunoregulatory microglia polarization (Saavedra, 2012; Rodriguez-Perez et al, 2016; Torika et al, 2016). The classical Ang II/AT1/Nox pro-oxidative and pro-inflammatory axis plays a major role in the RAS effects both in the brain and peripheral tissues.…”

Section: The Role Of Other Angiotensin Receptors In Regulation Of Micmentioning

confidence: 72%

Brain Renin-Angiotensin System and Microglial Polarization: Implications for Aging and Neurodegeneration

Labandeira‐Garcia

Rodríguez‐Pérez

Garrido‐Gil

et al. 2017

Front. Aging Neurosci.

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198

182

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Microglia can transform into proinflammatory/classically activated (M1) or anti-inflammatory/alternatively activated (M2) phenotypes following environmental signals related to physiological conditions or brain lesions. An adequate transition from the M1 (proinflammatory) to M2 (immunoregulatory) phenotype is necessary to counteract brain damage. Several factors involved in microglial polarization have already been identified. However, the effects of the brain renin-angiotensin system (RAS) on microglial polarization are less known. It is well known that there is a “classical” circulating RAS; however, a second RAS (local or tissue RAS) has been observed in many tissues, including brain. The locally formed angiotensin is involved in local pathological changes of these tissues and modulates immune cells, which are equipped with all the components of the RAS. There are also recent data showing that brain RAS plays a major role in microglial polarization. Level of microglial NADPH-oxidase (Nox) activation is a major regulator of the shift between M1/proinflammatory and M2/immunoregulatory microglial phenotypes so that Nox activation promotes the proinflammatory and inhibits the immunoregulatory phenotype. Angiotensin II (Ang II), via its type 1 receptor (AT1), is a major activator of the NADPH-oxidase complex, leading to pro-oxidative and pro-inflammatory effects. However, these effects are counteracted by a RAS opposite arm constituted by Angiotensin II/AT2 receptor signaling and Angiotensin 1–7/Mas receptor (MasR) signaling. In addition, activation of prorenin-renin receptors may contribute to activation of the proinflammatory phenotype. Aged brains showed upregulation of AT1 and downregulation of AT2 receptor expression, which may contribute to a pro-oxidative pro-inflammatory state and the increase in neuron vulnerability. Several recent studies have shown interactions between the brain RAS and different factors involved in microglial polarization, such as estrogens, Rho kinase (ROCK), insulin-like growth factor-1 (IGF-1), tumor necrosis factor α (TNF)-α, iron, peroxisome proliferator-activated receptor gamma, and toll-like receptors (TLRs). Metabolic reprogramming has recently been involved in the regulation of the neuroinflammatory response. Interestingly, we have recently observed a mitochondrial RAS, which is altered in aged brains. In conclusion, dysregulation of brain RAS plays a major role in aging-related changes and neurodegeneration by exacerbation of oxidative stress (OS) and neuroinflammation, which may be attenuated by pharmacological manipulation of RAS components.

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Section: The Role Of Other Angiotensin Receptors In Regulation Of Micmentioning

confidence: 72%

Brain Renin-Angiotensin System and Microglial Polarization: Implications for Aging and Neurodegeneration

Labandeira‐Garcia

Rodríguez‐Pérez

Garrido‐Gil

et al. 2017

Front. Aging Neurosci.

Self Cite

198

182

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“…We also investigated the effects of gangliosides on the production of microglial IGF-1, a growth factor produced by both neurons and glial cells with neuroprotective, anti-inflammatory and reparative roles [5,60,99]. Microglia is a major source of IGF-1 in the brain [100], especially in conditions that stimulate the acquisition by microglia of an M2-like immunoregulatory/reparative phenotype [101]. We found that expression of IGF-1 mRNA was not affected by exogenous GM1.…”

Section: Discussionmentioning

confidence: 94%

“…Primary mixed glial cultures from P0.5-P1.5 mice (C57BL/6J or FVB/NJ strain) and rats (Sprague Dawley) were prepared following the method described by [46]. In brief, cerebral cortices were enzymatically and mechanically dissociated and cells were seeded in DMEM/F12 medium supplemented with 10% FBS, 100…”

Section: Primary Cultures and Cell Linesmentioning

confidence: 99%

Anti-inflammatory role of GM1 and modulatory effects of gangliosides on microglia functions

Galleguillos

Qian

Steinberg

et al. 2020

Preprint

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Gangliosides are sialic acid-containing glycosphingolipids highly enriched in the brain. Located mainly at the plasma membrane, gangliosides play important roles in signaling and cell-to-cell communication. Lack of gangliosides causes severe early onset neurodegenerative disorders, while more subtle deficits have been reported in Parkinson's disease and in Huntington's disease, two misfolded protein diseases with a neuroinflammatory component. On the other hand, administration of ganglioside GM1 provides neuroprotection in both diseases and in several other models of neuronal insult. While most studies have focused on the role of endogenous gangliosides and the effects of exogenously administered GM1 in neurons, their contribution to microglia functions that are affected in neurodegenerative conditions is largely unexplored.Microglia are the immune cells of the brain and play important homeostatic functions in health and disease. In this study, we show that administration of exogenous GM1 exerts a potent antiinflammatory effect on microglia activated with LPS, IL-1β or upon phagocytosis of latex beads.These effects are partially reproduced by L-t-PDMP, a compound that stimulates the activity of the ganglioside biosynthetic pathway, while inhibition of ganglioside synthesis with GENZ-123346 increases microglial transcriptional response to LPS. We further show that administration of GM1 increases the uptake of apoptotic bodies and latex beads by microglia, as well as microglia migration and chemotaxis in response to ATP. On the contrary, decreasing microglial ganglioside levels results in a partial impairment in both microglial activities. Finally, increasing cellular ganglioside levels results in decreased expression and secretion of microglial brain derived neurotrophic factor (BDNF). Altogether, our data suggest that gangliosides are important modulators of microglia functions that are crucial to healthy brain homeostasis, and reveal that administration of ganglioside GM1 exerts an important anti-inflammatory activity that could be exploited therapeutically.

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“…In contrast to healthy adult and inflammation‐activated cells, neonatal CD11c + microglia show unique myelinogenic and neurogenic phenotypes (Wlodarczyk et al, ). These cells are the major source of IGF‐1 (Rodriguez‐Perez, Borrajo, Diaz‐Ruiz, Garrido‐Gil, & Labandeira‐Garcia, ), and its selective depletion from CD11c + microglia leads to impairment of primary myelination (Wlodarczyk et al, ). Interestingly, microglia produce and secrete IGF‐1 to support the survival of layer V cortical neurons during postnatal development (Ueno et al, ), yet OLs do this as well (Wilkins, Chandran, & Compston, ).…”

Section: Microglia Neuron and Ol Crosstalk Under Homeostatic Conditmentioning

confidence: 99%

Microglia roles in synaptic plasticity and myelination in homeostatic conditions and neurodevelopmental disorders

Bar

Barak

2019

Glia

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Microglia are the immune cells of the brain, involved in synapse formation, circuit sculpting, myelination, plasticity, and cognition. Being active players during early development as well as in adulthood, microglia affect other cells directly by their long processes and unique receptors and indirectly by secreting growth factors and cytokines. In this review, we discuss the roles of microglia in neurodevelopmental disorders, synaptic plasticity, myelination, and homeostatic conditions throughout human and mouse development. Within these processes, we specifically focus on the contribution of altered microglial interactions with neurons and oligodendrocytes, altered cytokine and growth factor activities, and alterations in the complement system. We conclude by highlighting future perspectives and providing an overview of future research on microglia.

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Crosstalk between insulin-like growth factor-1 and angiotensin-II in dopaminergic neurons and glial cells: role in neuroinflammation and aging

Cited by 56 publications

References 66 publications

Brain Renin-Angiotensin System and Microglial Polarization: Implications for Aging and Neurodegeneration

Brain Renin-Angiotensin System and Microglial Polarization: Implications for Aging and Neurodegeneration

Anti-inflammatory role of GM1 and modulatory effects of gangliosides on microglia functions

Microglia roles in synaptic plasticity and myelination in homeostatic conditions and neurodevelopmental disorders

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