Brain neurons develop in a serum and glial free environment: effects of transferrin, insulin- insulin-like growth factor-I and thyroid hormone on neuronal survival, growth and differentiation

Aizenman, Yair; Vellis, Jean de

doi:10.1016/0006-8993(87)90766-9

Cited by 252 publications

(98 citation statements)

References 41 publications

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“…This study demonstrates that insulin and insulin-like molecules IGF-I and IGF-II can inhibit apoptosis of E12 telencephalic cells. These results are supported by other studies illustrating that both IGF-I and IGF-II promote survival in many neuronal systems (Lindholm et al, 1996;D'Mello et al, 1993;Neff et al, 1993;Aizenman and de Vellis, 1987). The mechanism by which IGF-I mediates effects in other systems involves IGF-I receptor activation and PI3K pathways (Singleton et al, 1996a,b;Matthews and Feldman, 1996;D'Mello et al, 1997), and results presented here indicate a similar mechanism is used by immature telencephalic cells.…”

Section: Discussionsupporting

confidence: 90%

Trophic support promotes survival of bcl-x-deficient telencephalic cells in vitro

et al. 1998

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Survival of immature neurons is regulated by Bcl-x L , as targeted disruption of bcl-x significantly increases cell death in vivo and in vitro. Death of cultured bcl-x-deficient and wildtype telencephalic cells can be prevented by fetal calf serum or chemically-defined medium (ITS), suggesting trophic factors in these media potentiate survival through a pathway independent of Bcl-x L . Addition of trophic factors to basal medium revealed that insulin and insulin-like growth factors (IGFs), but not other trophic factors, reduced apoptosis of wild-type and bcl-x-deficient telencephalic cells. Antibodies raised against IGF-I receptors and wortmannin both attenuated the effects of IGF-I, indicating survival was mediated by IGF-I receptors and phosphatidylinositol 3'-kinase signaling, whereas effects of ITS were only partially reduced by these agents. The survival promoting effects of ITS were reduced in cells lacking both bcl-x and bcl-2, indicating Bcl-2 plays a supportive role to Bcl-x L in maintaining telencephalic cell survival. Furthermore, the ratio of expression of the pro-apoptotic bax gene to the anti-apoptotic bcl-2 gene was reduced in bcl-x-deficient cultures grown in ITS, suggesting that the interaction between these bcl-2 family members may, in part, regulate a Bcl-x L independent survival pathway. Finally, the pro-apoptotic bad gene does not appear to play a role in these interactions as targeted disruption of bad did not alter apoptosis in telencephalic cultures.

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Section: Discussionsupporting

confidence: 90%

Trophic support promotes survival of bcl-x-deficient telencephalic cells in vitro

et al. 1998

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“…In vitro studies have suggested many potential roles for Igf1 in brain development and function (34)(35)(36). The specific effects exerted by Igf1 in vivo, however, are determined by where and when the peptide and its receptor are actually expressed.…”

Section: Discussionmentioning

confidence: 99%

“…The protocol for in situ hybridization and the generation of 35 S-labeled sense and antisense RNA probes for IGF1 and GLUT4 were described previously (8,22). GLUT4 mRNA was quantified in Purkinje cells of WT and Igf1-null mice by a blinded observer counting grains overlying 50 cells per section in two to three sections for each mouse, with five to six mice per group.…”

Section: -Deoxy-d-glucose Uptake (2dgu)mentioning

confidence: 99%

Insulin-like growth factor 1 regulates developing brain glucose metabolism

Cheng

Reinhardt

Lee

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

186

113

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The brain has enormous anabolic needs during early postnatal development. This study presents multiple lines of evidence showing that endogenous brain insulin-like growth factor 1 (Igf1) serves an essential, insulin-like role in promoting neuronal glucose utilization and growth during this period. Brain 2-deoxy-D-[1-14 C]glucose uptake parallels Igf1 expression in wild-type mice and is profoundly reduced in Igf1؊͞؊ mice, particularly in those structures where Igf1 is normally most highly expressed. 2-Deoxy-D-[1-14 C]glucose is significantly reduced in synaptosomes prepared from Igf1؊͞؊ brains, and the deficit is corrected by inclusion of Igf1 in the incubation medium. The serine͞threonine kinase Akt͞ PKB is a major target of insulin-signaling in the regulation of glucose transport via the facilitative glucose transporter (GLUT4) and glycogen synthesis in peripheral tissues. Phosphorylation of Akt and GLUT4 expression are reduced in Igf1؊͞؊ neurons. Phosphorylation of glycogen synthase kinase 3␤ and glycogen accumulation also are reduced in Igf1؊͞؊ neurons. These data support the hypothesis that endogenous brain Igf1 serves an anabolic, insulin-like role in developing brain metabolism.mental retardation ͉ glycogen synthase kinase ͉ glucose transporter ͉ GLUT4 ͉ Akt T he brain requires enormous supplies of fuel to support neuroglial growth and process formation during early postnatal development. Murine and human brains consume over half the energy available to the organism as a whole during this critical period (1), when undernutrition may result in permanent intellectual deficit (2). How the developing brain competes so successfully with peripheral tissues for resources is unknown. Insulin preferentially enhances fuel and substrate utilization by peripheral tissues, but does not seem to be involved in the regulation of brain metabolism (3). Very little insulin is synthesized within the brain (4) and little circulating insulin crosses the blood-brain barrier (5). However, insulin-like growth factor 1 (Igf1), an insulin homologue, is abundant in the developing brain (6), where it is concentrated in large projection neurons (7-9). Igf1 and insulin receptors are also homologous, with nearly identical signal-transducing domains engaging many of the same intracellular pathways (10). The Igf1 receptor (Igf1R) is widely expressed in the brain (11)(12)(13)(14) where it is most abundant in Igf1-expressing neurons (15), suggesting a local autocrine͞paracrine mode of action for neuronal Igf1. Although Igf1's precise role in brain development is unknown, its importance seems clear because IGF1 gene deletion in humans results in mental retardation (16). Based on Igf1͞Igf1R expression patterns in the developing brain and on the functional homology with the insulin͞insulin receptor dyad, we hypothesized that neuronal Igf1 serves an anabolic, literally ''insulin-like'' role in brain development (17). To test this hypothesis, we investigated glucose utilization in Igf1-targeted gene deletion mice. Experimental ProceduresThe mice ...

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“…Therefore, we proceeded to examine SIRP␣ responses to such exogenous signals in GCPs, a preparation highly enriched in re-sealed, primarily axonal growth cones (Pfenninger et al, 1983;Lohse et al, 1996). Previous studies have shown that BDNF and IGF-1 stimulate axonal growth, and that GCPs contain functional receptors for them (Davies et al, 1986;Aizenman and De Vellis, 1987;Pfenninger et al, 2003). Therefore, we chose IGF-1 and BDNF to test the effects of growth factors on SIRP␣ in GCPs.…”

Section: Journal Of Cell Science 119 (1)mentioning

confidence: 99%

Functional analysis of SIRPα in the growth cone

Wang

Pfenninger

2006

Journal of Cell Science

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The `signal regulatory protein' SIRPα is an Ig superfamily, transmembrane glycoprotein with a pair of cytoplasmic domains that can bind the phosphatase SHP-2 when phosphorylated on tyrosine. SIRPα is prominent in growth cones of rat cortical neurons and located, together with the tetraspanin CD81, in the growth cone periphery. SIRPα is dynamically associated with Triton-X-100-sensitive, but Brij-98-resistant, lipid microdomains, which also contain CD81. Challenge of growth cones with the integrin-binding extracellular-matrix (ECM) protein, laminin, or with the growth factors, IGF-1 or BDNF, increases SIRPα phosphorylation and SHP-2 binding rapidly and transiently, via Src family kinase activation; phosphorylated SIRPα dissociates from the lipid microdomains. A cytoplasmic tail fragment of SIRPα (cSIRPα), when expressed in primary cortical neurons, also is phosphorylated and binds SHP-2. Expression of wild-type cSIRPα, but not of a phosphorylation-deficient mutant, substantially decreases IGF-1-stimulated axonal growth on laminin. On poly-D-lysine and in control conditions, axonal growth is slower than on laminin, but there is no further reduction in growth rate induced by the expression of cSIRPα. Thus, the effect of cSIRPα on axon growth is dependent upon integrin activation by laminin. These results suggest that SIRPα functions in the modulation of axonal growth by ECM molecules, such as laminin.

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Brain neurons develop in a serum and glial free environment: effects of transferrin, insulin- insulin-like growth factor-I and thyroid hormone on neuronal survival, growth and differentiation

Cited by 252 publications

References 41 publications

Trophic support promotes survival of bcl-x-deficient telencephalic cells in vitro

Trophic support promotes survival of bcl-x-deficient telencephalic cells in vitro

Insulin-like growth factor 1 regulates developing brain glucose metabolism

Functional analysis of SIRPα in the growth cone

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