Insulin-Like Growth Factor-1 and Neuroinflammation

Labandeira‐Garcia, Jose L.; Costa-Besada, Maria A.; Labandeira, Carmen M.; Villar-Cheda, Begoña; Rodríguez‐Pérez, Ana I.

doi:10.3389/fnagi.2017.00365

Cited by 171 publications

(145 citation statements)

References 105 publications

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“…Although many cell types can express IGF1, microglia are a major source in the brain (Suh et al, ; Labandeira‐Garcia et al, ) with high expression embryonically (Thion et al, ) and a re‐emergence with age, injury, or disease (O'Kusky and Ye, ) (Fig. ).…”

Section: Shared Pathways Of Microglia In Developmental and Disease Stmentioning

confidence: 99%

“…Of interest, overexpression of Igf1 increases hippocampal neurogenesis and synaptogenesis during postnatal development (Kusky et al, 2000), and IGF1 can restore synaptic deficits in iPSC-derived neurons from individuals with a neurodevelopmental disorder Phelan-McDermid syndrome (Shcheglovitov et al, 2013). Although many cell types can express IGF1, microglia are a major source in the brain (Suh et al, 2013;Labandeira-Garcia et al, 2017) with high expression embryonically (Thion et al, 2018) and a re-emergence with age, injury, or disease (O'Kusky and Ye, 2012) ( Fig. 3).…”

Section: Igf1mentioning

confidence: 99%

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Developmental roles of microglia: A window into mechanisms of disease

Anderson

Vetter

2018

Developmental Dynamics

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Microglia are engineers of the CNS both in health and disease. In addition to the canonical immunological roles of clearing damaging entities and limiting the spread of toxicity and death, microglia remodel the CNS throughout life. While they have been extensively studied in disease and injury, due to their highly variable functions, their precise role in these contexts still remains uncertain. Over the last decade we have greatly expanded our understanding of microglial function, including their essential homeostatic roles during development. Here, we review these developmental roles, identify parallels in disease, and speculate whether developmental mechanisms reemerge in disease and injury.

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Section: Shared Pathways Of Microglia In Developmental and Disease Stmentioning

confidence: 99%

Section: Igf1mentioning

confidence: 99%

Developmental roles of microglia: A window into mechanisms of disease

Anderson

Vetter

2018

Developmental Dynamics

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“…IGF-1 promotes the phagocytosis of AECs. IGF-1 signaling is involved in the inflammatory response (18); the role of non-professional phagocytosis in the inflammatory response has been reported (19). Thus, whether IGF-1 affects the phagocytosis of AECs, non-professional phagocytes, was investigated in the present study.…”

Section: Resultsmentioning

confidence: 89%

Upregulated IGF‑1 in the lungs of asthmatic mice originates from alveolar macrophages

Wang

et al. 2018

Mol Med Report

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Asthma is characterized by inflammation and remodeling of the airways. Insulin-like growth factor-1 (IGF-1) serves an important role in the repair of lung tissue injury and airway remodeling by elevating collagen and elastin content, increasing the thickness of smooth muscle and promoting the proliferation of lung epithelial and interstitial cells, as well as fibroblasts; however, the content of IGF-1 and its cellular origin in the lungs of patients with asthma remain unknown. In the present study, a mouse model of asthma was constructed. Following isolation of alveolar macrophages (AMs), the content of IGF-1 in lung tissue and bronchoalveolar lavage fluid (BALF) was detected by ELISA. The proliferation and phagocytosis of alveolar epithelial cells (AECs) stimulated by IGF-1 were detected by Cell Counting Kit-8 method and flow cytometry, respectively. In the present study, IGF-1 was upregulated in the lung tissues of asthmatic mice, and the content of IGF-1 in BALF was also elevated. Depletion of AMs by treating mice with 2-chloroadenosine via nose dripping reversed the increase of IGF-1 by 80% in lung tissues and by ~100% in BALF of asthmatic mice, suggesting that elevated IGF-1 in asthmatic mice predominantly originated from AMs. As IGF-1 promotes the proliferation and phagocytosis of AECs, AM-derived IGF-1 may serve an important role in the regulation of airway inflammation and remodeling in asthmatic mice.

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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].…”

Section: Discussionmentioning

confidence: 99%

“…As part of their homeostatic functions, microglia produce growth factors such as BDNF and IGF-1 that provide trophic support for and regulate the activity of neurons and other brain cells [60,61]. While both factors have been involved in neuroprotection, microglia BDNF secretion is also an established contributor to neuropathic pain [62].…”

Section: Exogenous Gm1 Does Not Affect Microglial Secretion Of Bdnf Amentioning

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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Insulin-Like Growth Factor-1 and Neuroinflammation

Cited by 171 publications

References 105 publications

Developmental roles of microglia: A window into mechanisms of disease

Developmental roles of microglia: A window into mechanisms of disease

Upregulated IGF‑1 in the lungs of asthmatic mice originates from alveolar macrophages

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

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