IGF-I deficient mice show reduced peripheral nerve conduction velocities and decreased axonal diameters and respond to exogenous IGF-I treatment

Gao, Wei‐Qiang; Shinsky, Natasha; Ingle, Gladys S.; Beck, Klaus D.; Elias, Kathleen A.; Powell-Braxton, Lyn

doi:10.1002/(sici)1097-4695(199904)39:1<142::aid-neu11>3.0.co;2-h

Cited by 91 publications

(50 citation statements)

References 38 publications

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“…IGF-1 plays an important role in the nervous system, stimulating postnatal brain growth (46), promoting neuron survival and growth (47,48), increasing the rate of axon regeneration in crush-injured sciatic nerve (49) and increasing the proliferation of oligodendrocytes (50). Lack of IGF-1 in knockout mice severely affects survival and maturation of neurons (51).…”

Section: Discussionmentioning

confidence: 99%

IPLEX Administration Improves Motor Neuron Survival and Ameliorates Motor Functions in a Severe Mouse Model of Spinal Muscular Atrophy

Murdocca¹,

Malgieri²,

Luchetti³

et al. 2012

Mol Med

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Spinal muscular atrophy (SMA) is an inherited neurodegenerative disorder and the first genetic cause of death in childhood. SMA is caused by low levels of survival motor neuron (SMN) protein that induce selective loss of α-motor neurons (MNs) in the spinal cord, resulting in progressive muscle atrophy and consequent respiratory failure. To date, no effective treatment is available to counteract the course of the disease. Among the different therapeutic strategies with potential clinical applications, the evaluation of trophic and/or protective agents able to antagonize MNs degeneration represents an attractive opportunity to develop valid therapies. Here we investigated the effects of IPLEX (recombinant human insulinlike growth factor 1 [rhIGF-1] complexed with recombinant human IGF-1 binding protein 3 [rhIGFBP-3]) on a severe mouse model of SMA. Interestingly, molecular and biochemical analyses of IGF-1 carried out in SMA mice before drug administration revealed marked reductions of IGF-1 circulating levels and hepatic mRNA expression. In this study, we found that perinatal administration of IPLEX, even if does not influence survival and body weight of mice, results in reduced degeneration of MNs, increased muscle fiber size and in amelioration of motor functions in SMA mice. Additionally, we show that phenotypic changes observed are not SMN-dependent, since no significant SMN modification was addressed in treated mice. Collectively, our data indicate IPLEX as a good therapeutic candidate to hinder the progression of the neurodegenerative process in SMA.

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Section: Discussionmentioning

confidence: 99%

IPLEX Administration Improves Motor Neuron Survival and Ameliorates Motor Functions in a Severe Mouse Model of Spinal Muscular Atrophy

Murdocca¹,

Malgieri²,

Luchetti³

et al. 2012

Mol Med

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“…Mice lacking IGF1 have abnormalities in sensory neurons (Gao et al, 1999), and show defective cortical dendritic growth (Cheng et al, 2003). IGFBP5 is a widely expressed protein whose role in vivo has not been clearly defined.…”

Section: Changes In Expression Of Genes Related To Axon Growthmentioning

confidence: 99%

Coordinated regulation of gene expression by Brn3a in developing sensory ganglia

et al. 2004

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Mice lacking the POU-domain transcription factor Brn3a exhibit marked defects in sensory axon growth and abnormal sensory apoptosis. We have determined the regulatory targets of Brn3a in the developing trigeminal ganglion using microarray analysis of Brn3a mutant mice. These results show that Brn3 mediates the coordinated expression of neurotransmitter systems, ion channels, structural components of axons and inter- and intracellular signaling systems. Loss of Brn3a also results in the ectopic expression of transcription factors normally detected in earlier developmental stages and in other areas of the nervous system. Target gene expression is normal in heterozygous mice, consistent with prior work showing that autoregulation by Brn3a results in gene dosage compensation. Detailed examination of the expression of several of these downstream genes reveals that the regulatory role of Brn3a in the trigeminal ganglion appears to be conserved in more posterior sensory ganglia but not in the CNS neurons that express this factor.

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“…On the other hand, transgenic mice over-expressing IGF-I show increased cell size and total brain myelin, and decreased apoptosis (Carson et al, 1993;Ye et al, 1995;Beck et al, 1995;Gao et al, 1999). Similarly, the analysis of the cochlea of Igf-1 null mice demonstrated that IGF-I participates in the maturation and maintenance of the inner ear (Camarero et al, 2001(Camarero et al, , 2002.…”

Section: Igf-i Has Trophic Actions On Postnatal Cochlear Development mentioning

confidence: 99%

Trophic effects of insulin-like growth factor-I (IGF-I) in the inner ear

et al. 2004

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IGF-I deficient mice show reduced peripheral nerve conduction velocities and decreased axonal diameters and respond to exogenous IGF-I treatment

Cited by 91 publications

References 38 publications

IPLEX Administration Improves Motor Neuron Survival and Ameliorates Motor Functions in a Severe Mouse Model of Spinal Muscular Atrophy

IPLEX Administration Improves Motor Neuron Survival and Ameliorates Motor Functions in a Severe Mouse Model of Spinal Muscular Atrophy

Coordinated regulation of gene expression by Brn3a in developing sensory ganglia

Trophic effects of insulin-like growth factor-I (IGF-I) in the inner ear

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