Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/ijms22010256
Keywords
hypoxia-ischemia; growth hormone; IGF-1; cerebellum; neuroprotection
Funding
- Programa de Apoyo a Proyectos de Investigacion e Innovacion Tecnologica de la Direccion General de Asuntos del Personal Academico (PAPIIT-DGAPA-UNAM) [IN207018, IN208419, IN227020]
- UNAM [1130-202-002]
- Universidad Nacional Autonoma de Mexico (UNAM
- Mexico City, Mexico)
- Consejo Nacional de Ciencia y Tecnologia (CONACYT, Mexico City, Mexico) [285004]
- CONACYT [696979, 475619, CVU-267642]
- Alejandro Bayon Fund
Ask authors/readers for more resources
GH and IGF-1 have been shown to have protective effects against neural damage, leading to increased cell viability and decreased apoptosis and necrosis in embryonic chicken cerebellar cell cultures exposed to acute HI injury.
It has been reported that growth hormone (GH) and insulin-like growth factor 1 (IGF-1) exert protective and regenerative actions in response to neural damage. It is also known that these peptides are expressed locally in nervous tissues. When the central nervous system (CNS) is exposed to hypoxia-ischemia (HI), both GH and IGF-1 are upregulated in several brain areas. In this study, we explored the neuroprotective effects of GH and IGF-1 administration as well as the involvement of these endogenously expressed hormones in embryonic chicken cerebellar cell cultures exposed to an acute HI injury. To induce neural damage, primary cultures were first incubated under hypoxic-ischemic (<5% O-2, 1g/L glucose) conditions for 12 h (HI), and then incubated under normal oxygenation and glucose conditions (HI + Ox) for another 24 h. GH and IGF-1 were added either during or after HI, and their effect upon cell viability, apoptosis, or necrosis was evaluated. In comparison with normal controls (Nx, 100%), a significant decrease of cell viability (54.1 +/- 2.1%) and substantial increases in caspase-3 activity (178.6 +/- 8.7%) and LDH release (538.7 +/- 87.8%) were observed in the HI + Ox group. On the other hand, both GH and IGF-1 treatments after injury (HI + Ox) significantly increased cell viability (77.2 +/- 4.3% and 72.3 +/- 3.9%, respectively) and decreased both caspase-3 activity (118.2 +/- 3.8% and 127.5 +/- 6.6%, respectively) and LDH release (180.3 +/- 21.8% and 261.6 +/- 33.9%, respectively). Incubation under HI + Ox conditions provoked an important increase in the local expression of GH (3.2-fold) and IGF-1 (2.5-fold) mRNAs. However, GH gene silencing with a specific small-interfering RNAs (siRNAs) decreased both GH and IGF-1 mRNA expression (1.7-fold and 0.9-fold, respectively) in the HI + Ox group, indicating that GH regulates IGF-1 expression under these incubation conditions. In addition, GH knockdown significantly reduced cell viability (35.9 +/- 2.1%) and substantially increased necrosis, as determined by LDH release (1011 +/- 276.6%). In contrast, treatments with GH and IGF-1 stimulated a partial recovery of cell viability (45.2 +/- 3.7% and 53.7 +/- 3.2%) and significantly diminished the release of LDH (320.1 +/- 25.4% and 421.7 +/- 62.2%), respectively. Our results show that GH, either exogenously administered and/or locally expressed, can act as a neuroprotective factor in response to hypoxic-ischemic injury, and that this effect may be mediated, at least partially, through IGF-1 expression.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available