The role of Insulin-Like Growth Factor 1 (IGF-1) in brain development, maturation and neuroplasticity

Dyer, Adam H.; Vahdatpour, Cyrus; Sanfeliu, Albert; Tropea, Daniela

doi:10.1016/j.neuroscience.2016.03.056

Cited by 256 publications

(189 citation statements)

References 132 publications

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“…Overall, these data suggest increased habituation or non-associative learning in AB over TL larvae. A recent study in zebrafish larvae showed that IGF1 increases acoustic startle habituation through activation of the IGF1 receptor thereby regulating synaptic strength [40], in line with the proposed role of IGF1 in neuronal plasticity [29]. Hence, we hypothesise here that the difference in habituation between AB and TL may be related to higher levels of expression of igf1 , that we observed in AB compared to TL larvae.…”

Section: Discussionsupporting

confidence: 81%

Further characterisation of differences between TL and AB zebrafish (Danio rerio): Gene expression, physiology and behaviour at day 5 of the larval stage

et al. 2017

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Zebrafish (Danio rerio) have become popular as model organism in research. Many strains are readily available, which not only differ morphologically, but also genetically, physiologically and behaviourally. Here, we focus on the AB and Tupfel long-fin (TL) strain for which we have previously shown that adults differ in baseline hypothalamus-pituitary-interrenal (HPI)-axis activity (AB higher than TL) affecting inhibitory avoidance behaviour (absent in AB). To assess whether strain differences are already present in early life stages, we compared baseline HPI-axis related gene expression as well as cortisol levels, (neuro)development related as well as (innate) immune system related gene expression, and light-dark as well as startle behaviour in larvae 5 days post fertilisation. The data show that AB and TL larvae differ in baseline HPI-axis activity (AB higher than TL), expression of (neuro)development and immune system related genes (AB higher than TL), habituation to acoustic/vibrational stimuli (AB habituate faster than TL) and light-dark induced changes in motor behaviour (AB stronger than TL). Our data show that already in larval stages differences exist between zebrafish of the AB and TL strain confirming and extending data of earlier studies. To what extent the mutation in connexin 41.8, leading to spots rather than stripes in TL, but also (possibly) affecting eye, heart and brain function, is involved in the expression of (some of) these differences needs to be studied. These results emphasise that differences between strains need to be taken into account to enhance reproducibility both within, and between, laboratories.

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Section: Discussionsupporting

confidence: 81%

Further characterisation of differences between TL and AB zebrafish (Danio rerio): Gene expression, physiology and behaviour at day 5 of the larval stage

et al. 2017

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“…When insulin binds the extracellular α-subunits of insulin receptors, it induces the dimerization of the intracellular β-subunits, which activates intrinsic tyrosine kinases and causes receptor autophosphorylation. Insulin-like growth factor 1 (IGF1) also binds and activates insulin receptors, and both insulin and IGF receptors can initiate many of the same trophic actions 22,23 .…”

Section: Insulin Actionmentioning

confidence: 99%

Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums

et al. 2018

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Considerable overlap has been identified in the risk factors, comorbidities and putative pathophysiological mechanisms of Alzheimer disease and related dementias (ADRDs) and type 2 diabetes mellitus (T2DM), two of the most pressing epidemics of our time. Much is known about the biology of each condition, but whether T2DM and ADRDs are parallel phenomena arising from coincidental roots in ageing or synergistic diseases linked by vicious pathophysiological cycles remains unclear. Insulin resistance is a core feature of T2DM and is emerging as a potentially important feature of ADRDs. Here, we review key observations and experimental data on insulin signalling in the brain, highlighting its actions in neurons and glia. In addition, we define the concept of ‘brain insulin resistance’ and review the growing, although still inconsistent, literature concerning cognitive impairment and neuropathological abnormalities in T2DM, obesity and insulin resistance. Lastly, we review evidence of intrinsic brain insulin resistance in ADRDs. By expanding our understanding of the overlapping mechanisms of these conditions, we hope to accelerate the rational development of preventive, disease-modifying and symptomatic treatments for cognitive dysfunction in T2DM and ADRDs alike.

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“…This pathway can enhance the proliferation and development of cells by initiating the anti-apoptotic PI3K/Akt/mTOR and the mitogenic Ras/Raf/Mek/Erk pathways (21,22). The IGF1 pathway is associated with the growth, metastasis and clinical outcome of various cancers, including prostate cancer, gastric cancer, lung cancer and breast cancer (23)(24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

Upregulation of IGF1 by tumor-associated macrophages promotes the proliferation and migration of epithelial ovarian cancer cells

Liu

Wang

et al. 2017

Oncol Rep

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Abstract. Ovarian cancer (OC), of which epithelial ovarian cancer (EOC) is the most common, is the deadliest gynecological tumor because of the difficulties in detection at early stages, and metastasis and chemoresistance at advanced stages. Tumor-associated macrophages (TAMs) differentiate through alternative pathways and play important roles in tumor growth and metastasis. However, the underlying mechanism remains unclear. Here, we established a mouse TAM model using bone marrow monocytes and conditioned medium (CM) of TAMs to culture ID8 mouse EOC cells. The results showed that TAM CM accelerated the proliferation and migration of ID8 cells. In a previous study, gene chip analysis showed that human TAMs expressed significantly higher levels of insulinlike growth factor-1 (IGF1) than undifferentiated M0 myeloid cells. In the present study, we observed that the IGF1 level was higher in human EOC specimens than that in benign ovarian tumor specimens, and further analysis showed that a higher level of IGF1 was related to more advanced clinical stage and liver metastasis. Therefore, we hypothesized that TAMs may accelerate the proliferation and migration of EOC cells by upregulating IGF1. As expected, increased IGF1 expression at both the mRNA and protein levels was observed in ID8 cells cultured with TAM CM, whereas blockade of the IGF1 pathway in ID8 cells with an IGF1 neutralizing antibody effectively reversed the promotion of proliferation and migration. Finally, we inhibited the phosphorylation of insulin-like growth factor-1 receptor (IGF1R) and its downstream molecules Akt and Erk with the IGF1R inhibitor linsitinib, and observed that the treatment effectively suppressed the proliferation and migration of ID8 cells exposed to TAM CM. Thus, we demonstrated that TAMs may promote the growth and metastasis of EOC via the activation of the IGF1 pathway; thus, targeting the IGF1 pathway may be promising for EOC therapy.

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The role of Insulin-Like Growth Factor 1 (IGF-1) in brain development, maturation and neuroplasticity

Cited by 256 publications

References 132 publications

Further characterisation of differences between TL and AB zebrafish (Danio rerio): Gene expression, physiology and behaviour at day 5 of the larval stage

Further characterisation of differences between TL and AB zebrafish (Danio rerio): Gene expression, physiology and behaviour at day 5 of the larval stage

Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums

Upregulation of IGF1 by tumor-associated macrophages promotes the proliferation and migration of epithelial ovarian cancer cells

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