Different levels of neuroprotection by two insulin-like growth factor-I splice variants

We compared the neuroprotective effects of a liver-type isoform of insulin-like growth factor-I (IGF-IEa) and its splice variant, mechano-growth factor (MGF), isolated from active skeletal muscle. cDNAs of these peptides were injected into the facial muscle of adult rats prior to facial nerve avulsion. This resulted in significant neuroprotection of 88% and 37%, respectively, of motoneurons compared to control plasmid and avulsion-only groups. MGF is markedly more effective than the liver-type, systemic IGF-I for motoneuron survival, suggesting a major role for the peripheral target in adult neuronal maintenance and survival.Michael Aperghis, Ian P. Johnson, John Cannon, Shi-Yu Yang and Geoffrey Goldspin

Age, diet and injury affect the survival of facial motoneurons

Using the model of facial nerve avulsion, we have compared the effects of injury, age and diet on motoneuronal survival. One to four weeks after nerve avulsion, 50–75% motoneuron loss was quantified in ad libitum-fed rats aged 7 days (neonate), 6 months (adult) and 24 months (aging) at the time of injury. Evidence of apoptosis was found for neonatal rats at 3 days post-injury, but not for neonates examined 7 days or adult or aging rats examined 1 month after injury. Non-operated, ad libitum-fed rats showed no significant loss of facial motoneurons by 24 months. Surprisingly, non-operated rats whose food intake was restricted to 15 g standard rat chow per day from the age of 6 months lost 50% of their motoneurons by 24 months. Facial nerve avulsion of 24-month-old rats raised on this restricted diet did not result in any additional loss of motoneurons one month after injury. These results challenge the common view that aging results in neuronal loss and that dietary restriction is universally beneficial.M. Aperghis, I. P. Johnson, N. Patel, A. Khadir, J. Cannon and G. Goldspin

The effects of two weeks of recombinant growth hormone administration on the response of IGF-I and N-terminal pro-peptide of collagen type III (P-III-NP) during a single bout of high resistance exercise in resistance trained young men

Recombinant human growth hormone (rhGH) is used by some athletes and body builders with the aim of enhancing performance, building muscle and improving physique. Detection of the misuse of rhGH has proved difficult for a number of reasons. One of these is the effect of preceding exercise. In this randomised, double blind placebo-controlled study, we determined the effects of rhGH administration in male amateur athletes on two candidate markers of rhGH abuse, IGF-I and N-terminal pro-peptide of collagen type III (P-III-NP), following a bout of weightlifting exercise

Serum IGF-I levels and IGF-I gene splicing in muscle of healthy young males receiving rhGH

Objective: Elevated growth hormone (GH) levels lead to increased circulating insulin-like growth factor-I (IGF-I), but the effects oil localised muscle IGF-I splice variant expression is not known. The effects of rhGH administration. with or without an acute bout Of high resistance exercise, were measured oil serum IGF-I and oil the mRNA levels of IGF-I splice variants in the vastus lateralis muscle of healthy young men. Design: The Study was a randomised double blind trial with a crossover design. Seven subjects were randomly assigned to a group receiving daily injections of rhGH (0.075 IU kg(-1) day(-1)) or placebo for a two week period. Following a one month washout. the groups were reversed. Results: Administration of rhGH increased circulating IGF-I from 31.8 +/- 3.2 to 109 +/- 5.4 nmol/L (p <0.05). There was no effect of the exercise bout. RNA was extracted from muscle biopsies obtained from exercised and non-exercised legs 2.5 h after the cessation of the exercise. Transcript expression was measured using Real-time QPCR. There was no effect of either exercise or rhGH administration oil IGF-I 5' (Class 1 or Class 2) or 3' (IGF-IEa, or MGF) transcripts. Conclusion: Although rhGH administration has all effect oil liver IGF-I expression, as shown by increase ill circulating IGF-I. muscle IGF-I expression is unaffected ill Young healthy Subjects with normal GH profile. The findings contrast with those of a Previous Study in which GH deficient elderly men showed higher Muscle IGF-I 3' splice variant levels following rhGH administration with and without resistance training. Unlike in the liver, muscle Class 1 and 2 IGF-1 expression do not change significantly following administration of rhGH. (C) 2008 Elsevier Ltd. All rights reserved