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Open AccessArticle

Neuroprotective Effects of Growth Hormone (GH) and Insulin-Like Growth Factor Type 1 (IGF-1) after Hypoxic-Ischemic Injury in Chicken Cerebellar Cell Cultures

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Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro 76230, Mexico
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Department of Molecular, Cellular and Developmental Biology, The University of Michigan, Ann Arbor, MI 48109, USA
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(1), 256; https://doi.org/10.3390/ijms22010256
Received: 30 November 2020 / Revised: 21 December 2020 / Accepted: 22 December 2020 / Published: 29 December 2020
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% O2, 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. View Full-Text
Keywords: hypoxia-ischemia; growth hormone; IGF-1; cerebellum; neuroprotection hypoxia-ischemia; growth hormone; IGF-1; cerebellum; neuroprotection
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MDPI and ACS Style

Baltazar-Lara, R.; Ávila-Mendoza, J.; Martínez-Moreno, C.G.; Carranza, M.; Pech-Pool, S.; Vázquez-Martínez, O.; Díaz-Muñoz, M.; Luna, M.; Arámburo, C. Neuroprotective Effects of Growth Hormone (GH) and Insulin-Like Growth Factor Type 1 (IGF-1) after Hypoxic-Ischemic Injury in Chicken Cerebellar Cell Cultures. Int. J. Mol. Sci. 2021, 22, 256. https://doi.org/10.3390/ijms22010256

AMA Style

Baltazar-Lara R, Ávila-Mendoza J, Martínez-Moreno CG, Carranza M, Pech-Pool S, Vázquez-Martínez O, Díaz-Muñoz M, Luna M, Arámburo C. Neuroprotective Effects of Growth Hormone (GH) and Insulin-Like Growth Factor Type 1 (IGF-1) after Hypoxic-Ischemic Injury in Chicken Cerebellar Cell Cultures. International Journal of Molecular Sciences. 2021; 22(1):256. https://doi.org/10.3390/ijms22010256

Chicago/Turabian Style

Baltazar-Lara, Rosario; Ávila-Mendoza, José; Martínez-Moreno, Carlos G.; Carranza, Martha; Pech-Pool, Santiago; Vázquez-Martínez, Olivia; Díaz-Muñoz, Mauricio; Luna, Maricela; Arámburo, Carlos. 2021. "Neuroprotective Effects of Growth Hormone (GH) and Insulin-Like Growth Factor Type 1 (IGF-1) after Hypoxic-Ischemic Injury in Chicken Cerebellar Cell Cultures" Int. J. Mol. Sci. 22, no. 1: 256. https://doi.org/10.3390/ijms22010256

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