Growth hormone and aging

Les alteracions vasculars i degeneratives del sistema nerviós central (SNC) són dues de les causes més comunes de malaltia i de mort entre la gent gran; ambdues es correlacionen amb l'edat, amb la deficiència en GH, i poden afectar les funcions fisiològiques de la població d'edat avançada. Amb la finalitat de clarificar els efectes de la GH en el metabolisme, en els vasos i en el SNC, hem dut a terme un estudi in vivo utilitzant rates vellesWistar tractades crònicament amb GH. Les rates velles varen presentar un augment en el pes de greix i una disminució de l'índex específic de gravetat (SGI) (p < 0,05) en comparar-les amb les rates adultes no tractades. La GH va reduir el pes en greix (p < 0,05), i va mostrar també una tendència a augmentar l'SGI. Es va analitzar també la resposta de diverses substàncies vasoactives en els anells aòrtics, i es va demostrar una disminució de la vasodilatació per acetilcolina i isoprenalina (p < 0,05) en els animals vells. La contracció induïda per acetilcolina+L-NAME era més alta en els animals vells que en els adults. L'administració de GH millorava les respostes vasodilatadores (p < 0,05) mentre que tendia a reduïr les respostes vasoconstrictores. L'àrea aòrtica mitja augmentava també en les rates velles, mentre que la GH reduïa aquest paràmetre (p < 0,05). Les poblacions neuronals es reduïen en els hipocamps de les rates velles en comparar-les amb les joves. Aquesta reducció estava asociada a un augment dels nucleosomes i a una reducció de Bcl2 en el cervell. Les caspases 3 i 9 també varen augmentar. El tractament amb GH va augmentar significativament el nombre de neurones i va reduir els nucleosomes i les caspases i augmentar el Bcl2. En conclusió, el tractament perGHindueix l'aparició d'efectes beneficiosos en la composició del cos i ha restablert també les funcions cerebrals i vasculars en les rates velles.Vascular and degenerative alterations of the central nervous system (CNS) are two of the most common reasons for illness and death in elderly people; they exhibit an age-related GH deficiency that can affect their physiological functions. A study was conducted under chronic in vivo conditions using old Wistar rats, in order to clarify the effects of GH on the metabolism, vessels, and the CNS. The old rats showed an increased fat weight and a decreased Specific Gravity Index (SGI) (p < 0.05), as compared to the adult animals. GH reduced the fat weight (p < 0.05) and tended to increase the SGI (N.S.). The response to several vasoactive substances in aortic rings showed impaired vasodilatation to Acetylcholine and Isoprenaline (p < 0.05) in the old animals. Contraction, induced by Acetylcholine+ L-NAME, was higher in the old rats than in the adults. GH administration improved the vasodilatory responses (p < 0.05) and tended to reduce the constrictory responses. The aortic media area was increased in the old rats, and GH reduced this parameter (p < 0.05). The neuronal populations were reduced in the hippocampi of the old rats as compared to the young ones. This reduction was associated with an increase in nucleosomes and a reduction in Bcl2 in the brain. An increase was also detected in caspases 3 and 9. GH treatment was able to significantly enhance the number of neurons by reducing the nucleosomes and the caspases and by increasing Bcl2. In conclusion,GHtreatment was able to show beneficial effects on body composition and was able to restore both vascular and brain functions in the old rats

Genome-Wide Interrogation of Mammalian Stem Cell Fate Determinants by Nested Chromosome Deletions

Understanding the function of important DNA elements in mammalian stem cell genomes would be enhanced by the availability of deletion collections in which segmental haploidies are precisely characterized. Using a modified Cre-loxP–based system, we now report the creation and characterization of a collection of ∼1,300 independent embryonic stem cell (ESC) clones enriched for nested chromosomal deletions. Mapping experiments indicate that this collection spans over 25% of the mouse genome with good representative coverage of protein-coding genes, regulatory RNAs, and other non-coding sequences. This collection of clones was screened for in vitro defects in differentiation of ESC into embryoid bodies (EB). Several putative novel haploinsufficient regions, critical for EB development, were identified. Functional characterization of one of these regions, through BAC complementation, identified the ribosomal gene Rps14 as a novel haploinsufficient determinant of embryoid body formation. This new library of chromosomal deletions in ESC (DelES: http://bioinfo.iric.ca/deles) will serve as a unique resource for elucidation of novel protein-coding and non-coding regulators of ESC activity

Zebrafish hoxd4a Acts Upstream of meis1.1 to Direct Vasculogenesis, Angiogenesis and Hematopoiesis

10.1371/journal.pone.0058857PLoS ONE83

Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes

<p>Abstract</p> <p>Background</p> <p>Human hemangiosarcoma (HSA) tends to have a poor prognosis; its tumorigenesis has not been elucidated, as there is a dearth of HSA clinical specimens and no experimental model for HSA. However, the incidence of spontaneous HSA is relatively high in canines; therefore, canine HSA has been useful in the study of human HSA. Recently, the production of angiogenic growth factors and their receptors in human and canine HSA has been reported. Moreover, the growth-factor environment of HSA is very similar to that of pathophysiological angiogenesis, which some homeobox genes regulate in the transcription of angiogenic molecules. In the present study, we established 6 xenograft canine HSA tumors and detected the expression of growth factors, their receptors, and angiogenic homeobox genes.</p> <p>Methods</p> <p>Six primary canine HSAs were xenografted to nude mice subcutaneously and serially transplanted. Subsequently, the expressions of vascular endothelial growth factor (VEGF)-A, basic fibroblast growth factors (bFGF), flt-1 and flk-1 (receptors of VEGF-A), FGFR-1, and angiogenic homeobox genes HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 were investigated in original and xenograft tumors by histopathology, immunostaining, and reverse transcription polymerase chain reaction (RT-PCR), using canine-specific primer sets.</p> <p>Results</p> <p>Histopathologically, xenograft tumors comprised a proliferation of neoplastic cells that were varied in shape, from spindle-shaped and polygonal to ovoid; some vascular-like structures and vascular clefts of channels were observed, similar to those in the original tumors. The expression of endothelial markers (CD31 and vWF) was detected in xenograft tumors by immunohistochemistry and RT-PCR. Moreover, the expression of VEGF-A, bFGF, flt-1, flk-1, FGFR-1, HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 was detected in xenograft tumors. Interestingly, expressions of bFGF tended to be higher in 3 of the xenograft HSA tumors than in the other tumors.</p> <p>Conclusion</p> <p>We established 6 xenograft canine HSA tumors in nude mice and found that the expressions of angiogenic growth factors and their receptors in xenograft HSAs were similar to those in spontaneous HSA. Furthermore, we detected the expression of angiogenic homeobox genes; therefore, xenograft models may be useful in analyzing malignant growth in HSA.</p

Role of astroglia in estrogen regulation of synaptic plasticity and brain repair

Astroglia are targets for estrogen and testosterone and are apparently involved in the action of sex steroids on the brain. Sex hormones induce changes in the expression of glial fibrillary acidic protein, the growth of astrocytic processes, and the degree of apposition of astroglial processes to neuronal membranes in the rat hypothalamus. These changes are linked to modifications in the number of synaptic inputs to hypothalamic neurons. These findings suggest that astrocytes may participate in the genesis of androgen- induced sex differences in synaptic connectivity and in estrogen-induced synaptic plasticity in the adult brain. Astrocytes and tanycytes may also participate in the cellular effects of sex steroids by releasing neuroactive substances and by regulating the local accumulation of specific growth factors, such as insulin-like growth factor-I, that are involved in estrogen- induced synaptic plasticity and estrogen-mediated neuroendocrine control. Astroglia may also be involved in regenerative and neuroprotective effects of sex steroids, since astroglia formation after brain injury or after peripheral nerve axotomy is regulated by sex hormones. Furthermore, the expression of aromatase, the enzyme that produces estrogen, is induced de novo in astrocytes in lesioned brain areas of adult male and female rodents. Since astroglia do not express aromatase under normal circumstances, the induction of this enzyme may be part of the program of glial activation to cope with the new conditions of the neural tissue after injury. Given the neuroprotective and growth-promoting effects of estrogen after injury, the local production of this steroid may be a relevant component of the reparative process.Peer Reviewe