Insulin-Like Growth Factor I Stimulates Dendritic Growth in Primary Somatosensory Cortex

Niblock, Mary M.; Brunso‐Bechtold, Judy K.; Riddle, David R.

doi:10.1523/jneurosci.20-11-04165.2000

Cited by 174 publications

(123 citation statements)

References 68 publications

Supporting

Mentioning

112

Contrasting

Unclassified

Order By: Relevance

“…2 A). In addition to neuronal activity, several secreted factors, including BDNF and insulin-like growth factor (IGF), are known to promote dendrite growth (4,22). Although insulin can activate GGT in non-neuronal cells (23,24), we found that neither insulin nor IGF-1 had any effect on GGT activity under our experimental conditions (Fig.…”

Section: Activation Of Ggt By Neuronal Activity or Bdnfmentioning

confidence: 68%

TrkB-mediated activation of geranylgeranyltransferase I promotes dendritic morphogenesis

Zhou

Liang

et al. 2008

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

View full text Add to dashboard Cite

Dendrite morphogenesis is regulated by neuronal activity or neurotrophins, which may function by activating intrinsic signaling proteins, including Rho family GTPases. Here we report that activity-and brain-derived neurotrophic factor (BDNF)-dependent dendritic morphogenesis requires activation of geranylgeranyltransferase I (GGT), a prenyltransferase that mediates lipid modification of Rho GTPases. Dendritic arborization in cultured hippocampal neurons was promoted by over-expression of GGT, and reduced by inhibition or down-regulation of GGT. Furthermore, GGT was activated by neuronal depolarization or BDNF, both of which promote dendritic arborization, in cultured hippocampal neurons. Moreover, exploration of a novel environment caused activation of GGT in the mice hippocampus, suggesting that neural activity activates GGT in vivo. Interestingly, GGT was physically associated with tropomyosin-related kinase B (TrkB), the receptor for BDNF, and this association was enhanced by depolarization. Disrupting the GGT-TrkB interaction or down-regulating GGT activity attenuated depolarization-or BDNF-induced dendrite development. Finally, the GGT effect on dendrite arborization was prevented by over-expressing Rac1 with the prenylation site deleted or mutated. Thus depolarization-or BDNF-dependent dendrite development may be mediated by GGT-induced prenylation of Rho GTPases.BDNF ͉ dendrite ͉ neuronal activity ͉ Rac ͉ prenylation D endritic morphogenesis is a critical step for establishing neural circuits. The growth and branching of dendritic arbors are controlled by both external signals and intracellular pathways (1, 2). Neuronal activity and neurotrophins, such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3, are known to regulate dendrite development through multiple signaling pathways, leading to cytoskeletal reorganization or gene expression required for dendritic growth (2-7). For example, members of the Rho family of small GTPases, including Rac1, Cdc42, and RhoA, are important for distinct aspects of dendrite development by modulating actin cytoskeleton (8, 9). Activation of Rho A attenuates dendrite growth and branching, whereas activation of Rac1 facilitates dendrite growth (8, 10, 11). Importantly, dendrite growth increased by visual activity requires Rho GTPases (12) and BDNF-dependent dendritic growth may be mediated by Rac1 (13). Thus, Rho GTPase may mediate the effects of BDNF or neuronal activity on dendrite development. However, the mechanism by which BDNF and activity regulate Rho GTPases remains largely unknown.The Rho GTPase cycles between a GTP-bound active state and a GDP-bound inactive state, and this process is regulated by GTPase activating proteins and guanine nucleotide exchange factors (GEFs) (14, 15). Importantly, GTPases need to be translocated from the cytosol to the membrane for their activation (16,17). This is achieved by prenylation, a reaction mainly catalyzed by farnesyltransferase (FT) or geranylgeranyltransferase I (GGT), which acts to covalently couple a lipid m...

show abstract

Section: Activation Of Ggt By Neuronal Activity or Bdnfmentioning

confidence: 68%

TrkB-mediated activation of geranylgeranyltransferase I promotes dendritic morphogenesis

Zhou

Liang

et al. 2008

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

View full text Add to dashboard Cite

show abstract

“…Evidence from animal research, suggests that growth hormone and IGF-I are important in neurodevelopment (20), and may therefore potentially be physiological mediators of the association of short birth length with schizophrenia (21).…”

Section: Methodological Issuesmentioning

confidence: 99%

“…While de novo mutations in paternal germ cells provide a reasonable or at least possible explanation for the paternal age-schizophrenia association, causal pathways explaining associations of size at birth and size in young adulthood with schizophrenia are largely unknown. However, since IGF-I is a major regulator of childhood growth (19) and is also influencing brain development in animal research (20), an intriguing hypothesis for future research is that IGF-I serves as a biological link between childhood growth, body size in adulthood and schizophrenia.…”

Section: Concluding Remarkmentioning

confidence: 99%

Paternal age, size at birth, and size in young adulthood – risk factors for schizophrenia

Rasmussen

2006

eur j endocrinol

View full text Add to dashboard Cite

It is appropriate to consider schizophrenia a neurodevelopmental disorder with its pathogenesis going back to gestation and early childhood. Schizophrenia is a rare disease and large cohorts are needed to study its etiology. The aim of this paper is to review the results of recent Swedish record-linkage studies with a focus on: (i) measures of fetal and childhood growth in relation to schizophrenia in adulthood and (ii) paternal age in relation to schizophrenia. A record-linkage was created between national registers, including the Medical Birth Register, the Military Service Conscription Register, and the Inpatient Hospital Discharge Register. More than 700 000 subjects born between 1973 and 1980 were followed in these registers from birth to 31 December 2001/2002. The results showed no evidence of an association between birth weight and schizophrenia. An association of birth length with schizophrenia was observed, with short babies showing the highest risk. Short stature and low BMI in young adulthood were associated with increased risk. Short babies who became tall, or developed high BMI as adults, were not at increased risk. In fully adjusted analyses, the risk of schizophrenia was 4.62 (95% confidence interval : 2.28; 9.36) times higher in subjects whose fathers were R50 years old and at time of conception than in subjects whose fathers were 21-24 years old. Growth and development in fetal life and childhood are influencing the risk of schizophrenia in adulthood, but the underlying causal pathways are still unknown. De novo mutations in the germ cells of older fathers may play a causal role in the etiology of some cases of schizophrenia.European Journal of Endocrinology 155 S65-S69

show abstract

“…However, the size and shape of neuritic arbors are influenced by environmental factors. Therefore, we examined whether NHE1 might also influence the effects of three agents that are known to promote neurite elongation and/or branching in mammalian central neurons, i.e., netrin-1 (Barallobre et al, 2005;Round and Stein, 2007), BDNF (Huang and Reichardt, 2001), and IGF-1 (Niblock et al, 2000). These experiments were performed on neocortical neurons obtained from P0.5 NHE1 ϩ/ϩ mice and their NHE1-null mutant (NHE1 Ϫ/Ϫ ) littermates and maintained in primary culture for 72 h.…”

Section: The Role Of Nhe1 In Trophic Factorstimulated Early Neurite Omentioning

confidence: 99%

Regulation of Early Neurite Morphogenesis by the Na+/H+ Exchanger NHE1

Sin¹,

Moniz²,

Ozog³

et al. 2009

Journal of Neuroscience

View full text Add to dashboard Cite

The ubiquitously expressed Na ϩ /H ϩ exchanger NHE1 plays an important role in regulating polarized membrane protrusion and directional motility in non-neuronal cells. Using NGF-differentiated PC12 cells and murine neocortical neurons in vitro, we now show that NHE1 plays a role in regulating early neurite morphogenesis. NHE1 was expressed in growth cones in which it gave rise to an elevated intracellular pH in actively extending neurites. The NHE1 inhibitor cariporide reversibly reduced growth cone filopodia number and the formation and elongation of neurites, especially branches, whereas the transient overexpression of full-length NHE1, but not NHE1 mutants deficient in either ion translocation activity or actin cytoskeletal anchoring, elicited opposite effects. In addition, compared with neocortical neurons obtained from wild-type littermates, neurons isolated from NHE1-null mice exhibited reductions in early neurite outgrowth, an effect that was rescued by overexpression of full-length NHE1 but not NHE1 mutants. Finally, the growth-promoting effects of netrin-1, but not BDNF or IGF-1, were markedly reduced by cariporide in wild-type neocortical neurons and were not observed in NHE1-null neurons. Although netrin-1 failed to increase growth cone intracellular pH or Na ϩ /H ϩ exchange activity, netrin-1-induced increases in early neurite outgrowth were restored in NHE1-null neurons transfected with full-length NHE1 but not an ion translocation-deficient mutant. Collectively, the results indicate that NHE1 participates in the regulation of early neurite morphogenesis and identify a novel role for NHE1 in the promotion of early neurite outgrowth by netrin-1.

show abstract

Insulin-Like Growth Factor I Stimulates Dendritic Growth in Primary Somatosensory Cortex

Cited by 174 publications

References 68 publications

TrkB-mediated activation of geranylgeranyltransferase I promotes dendritic morphogenesis

TrkB-mediated activation of geranylgeranyltransferase I promotes dendritic morphogenesis

Paternal age, size at birth, and size in young adulthood – risk factors for schizophrenia

Regulation of Early Neurite Morphogenesis by the Na+/H+ Exchanger NHE1

Contact Info

Product

Resources

About