scholarly journals Maternally Administered Cyclic Glycine-Proline Increases Insulin-Like Growth Factor-1 Bioavailability and Novelty Recognition in Developing Offspring

Endocrinology ◽  
2016 ◽  
Vol 157 (8) ◽  
pp. 3130-3139 ◽  
Author(s):  
Gagandeep Singh-Mallah ◽  
Kuljeet Singh ◽  
Christopher D. McMahon ◽  
Paul Harris ◽  
Margaret A. Brimble ◽  
...  

Cyclic glycine-proline (cGP), a metabolite of IGF-1, is an endogenous neuropeptide that improves memory in adult rats. The presence and concentrations of endogenous cGP, and its association with IGF-1 and IGF binding protein-3 (IGFBP-3) in rat milk and plasma, were evaluated during postnatal development. Maternal-infantile transfer of cGP during lactation and its efficacy on the memory of developing offspring were also investigated. Dams were gavaged with either cGP (3 mg/kg) or saline daily from postnatal days 8–22. Concentrations of cGP were measured in dams' milk, and concentrations of cGP, IGF-1, and IGFBP-3 were measured in the plasma of dams, pups, and young adults. The recognition memory, locomotor function, and anxiety-like behavior of offspring were evaluated using behavioral tests. Endogenous cGP was detected in rat milk, and its concentration was higher during peak lactation compared with late lactation. Comparisons within control groups showed low endogenous IGF-1 and IGFBP-3 and high endogenous cGP concentrations in the plasma of male pups. The reduced IGFBP-3 and increased cGP may be a response to increase the bioavailability of IGF-1 during infancy. Exogenous cGP showed oral bioavailability and effective maternal-infantile transfer through milk. Maternally transferred cGP also led to improved recognition memory in the developing offspring, possibly through increased IGF-1 bioavailability, with no effect on locomotor activity and anxiety-like behavior. These results show that cGP is an essential endogenous peptide during early postnatal development as it improves the bioavailability of IGF-1 during infancy. Furthermore, maternal cGP supplementation offers an effective and natural route of administration for improving memory in the developing offspring.

2001 ◽  
Vol 281 (6) ◽  
pp. G1378-G1384 ◽  
Author(s):  
C. A. Shoubridge ◽  
C.-B. Steeb ◽  
L. C. Read

In contrast to the adult gut, the immature intestine is refractory to subcutaneously infused insulin-like growth factor I (IGF-I). IGF binding protein (IGFBP) mRNA expression was characterized in intestinal tissues from 6-, 19-, and 90-day-old rats to determine if changes in local expression could account for this age-related change in IGF-I potency. For all age groups, IGFBP-3 to -6, but not IGFBP-1 or -2, were detected by Northern blot analysis. IGFBP-3, -4, and -5 were more intensely expressed in the 6-day-old rat intestine compared with weanling or adult tissue. In contrast, IGFBP-6 expression peaked at the time of weaning. In situ hybridization showed IGFBP-3 to -6 expression was confined to cells of the lamina propria and submucosa and also in the muscularis layer for IGFBP-5. Furthermore, the pattern of IGFBP-5 localization in the intestine changed with development. The findings indicate that the expression of IGFBP-3 to -6 is higher in the immature intestine compared with the adult intestine, suggesting locally produced IGFBPs may inhibit systemically derived IGF-I action in the intestine. Therefore, changes to local IGFBP expression may contribute to the varying response of the rat intestine to IGF-I peptides during postnatal development.


Author(s):  
Marta A. Lech ◽  
Kinga Kamińska ◽  
Monika Leśkiewicz ◽  
Elżbieta Lorenc-Koci ◽  
Zofia Rogóż

Abstract Background Preclinical and clinical studies have indicated that impaired endogenous synthesis of glutathione during early postnatal development plays a significant role in the pathophysiology of schizophrenia. Moreover, some studies have suggested that antidepressants are able to increase the activity of atypical antipsychotics which may efficiently improve the treatment of negative and cognitive symptoms of schizophrenia. Methods In the present study, we investigated the influence of repeated co-treatment with escitalopram and aripiprazole on the schizophrenia-like behavior and BDNF mRNA expression in adult rats exposed to glutathione deficit during early postnatal development. Male pups between the postnatal days p5–p16 were treated with the inhibitor of glutathione synthesis, BSO (L-buthionine-(S,R)-sulfoximine) and the dopamine uptake inhibitor, GBR 12,909 alone or in combination. Escitalopram and aripiprazole were given repeatedly for 21 days before the tests. On p90–92 rats were evaluated in the behavioral and biochemical tests. Results BSO given alone and together with GBR 12,909 induced deficits in the studied behavioral tests and decreased the expression of BDNF mRNA. Repeated aripiprazole administration at a higher dose reversed these behavioral deficits. Co-treatment with aripiprazole and an ineffective dose of escitalopram also abolished the behavioral deficits in the studied tests. Conclusion The obtained data indicated that the inhibition of glutathione synthesis in early postnatal development induced long-term deficits corresponding to schizophrenia-like behavior and decreased the BDNF mRNA expression in adult rats, and these behavioral deficits were reversed by repeated treatment with a higher dose of aripiprazole and also by co-treatment with aripiprazole and ineffective dose of escitalopram.


2006 ◽  
Vol 16 (2) ◽  
pp. 86-92 ◽  
Author(s):  
Tiffany G. Harris ◽  
Howard D. Strickler ◽  
Herbert Yu ◽  
Michael N. Pollak ◽  
E. Scott Monrad ◽  
...  

2005 ◽  
Vol 185 (3) ◽  
pp. 467-476 ◽  
Author(s):  
Teresa Priego ◽  
Miriam Granado ◽  
Ana Isabel Martín ◽  
Asunción López-Calderón ◽  
María Angeles Villanúa

The aim of this study was to investigate whether glucocorticoid administration had a beneficial effect on serum concentrations of insulin-like growth factor I (IGF-I) and on IGF-binding protein 3 (IGFBP-3) in rats injected with lipopolysaccharide (LPS). Adult male rats were injected with LPS or saline and pretreated with dexamethasone or saline. Dexamethasone administration decreased growth hormone (GH) receptor and IGF-I mRNA levels in the liver of control rats. LPS decreased GH receptor and IGF-I gene expression in the liver of saline-treated rats but not in the liver of dexamethasone-pretreated rats. In the kidney, GH receptor mRNA levels were not modified by dexamethasone or LPS treatment. However, LPS decreased renal IGF-I gene expression and dexamethasone pretreatment prevented this decrease. Serum concentrations of IGF-I were decreased by LPS, and dexamethasone pretreatment attenuated this effect. The gene expression of IGFBP-3 in the liver and kidney and its circulating levels were decreased by LPS. In control rats dexamethasone increased circulating IGFBP-3 and its gene expression in the liver, and decreased the proteolysis of this protein. Dexamethasone pretreatment attenuated the LPS-induced decrease in IGFBP-3 gene expression in the liver and prevented the LPS-induced decrease in IGFBP-3 gene expression in the kidney. Moreover, dexamethasone pretreatment attenuated the LPS-induced decrease in serum concentrations of IGFBP-3 and decreased the LPS-induced IGFBP-3 proteolysis in serum. In conclusion, dexamethasone pretreatment partially attenuates the inhibitory effect of LPS on serum IGF-I by blocking the decrease of its gene expression in the kidney as well as by attenuating the decrease in serum concentrations of IGFBP-3.


2007 ◽  
Vol 92 (9) ◽  
pp. 3660-3666 ◽  
Author(s):  
Iona Cheng ◽  
Katherine DeLellis Henderson ◽  
Christopher A. Haiman ◽  
Laurence N. Kolonel ◽  
Brian E. Henderson ◽  
...  

2000 ◽  
Vol 71 (2) ◽  
pp. 178-188
Author(s):  
Hong-Gu LEE ◽  
Renato Santa Ana VEGA ◽  
Long Thang PHUNG ◽  
Nobuyoshi MATSUNAGA ◽  
Hideto KUWAYAMA ◽  
...  

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