Growth hormone improves hippocampal adult cell survival and counteracts the inhibitory effect of prolonged sleep deprivation on cell proliferation.
Sleep deprivation (SD) produces numerous deleterious changes in brain cells, including apoptosis. It has been demonstrated that growth hormone (GH) stimulates cell growth and counteracts apoptosis, although this anti-apoptotic effect has not been tested against SD. To determine the protective effect of GH administration on cell proliferation and survival in the dentate gyrus (DG) of the hippocampus after sleep deprivation; we injected Wistar adult rats with a low dose of recombinant human GH (rhGH 5 ng/kg) per seven days and then we gently sleep deprived the animals for 48 consecutive hours. 5-Bromodeoxiuridine (BrdU) was administered to assess cell proliferation after the GH treatment and NeuN was used as marker of cell fate. Our results indicate that GH produced a three fold increase in the number of BrdU positive cells within the DG [Control = 1044 ± 106.38 cells, rhGH = 2952 ± 99.84 cells, P<0.01]. In contrast, 48 h of SD significantly reduced cell proliferation but this effect was antagonized by the GH administration [SD = 540 ± 18.3 cells, rhGH + SD = 1116 ± 84.48 cells, P<0.004]. Paradoxically, SD and GH administration increased cell survival separately but no significantly compared with control animals. However, cell survival was increased in animals treated with rhGH+SD compared to rats injected with saline solution [P<0.04]. Within the survival cells, the percentage of neurons was higher in SD animals [95%] compared with saline group, while this percentage (NeuN positive cells) was increased in animals treated with rhGH+SD [120%] compared with rhGH [25%] alone. Our findings indicate that GH strongly promotes cell proliferation in the adult brain and also protects the hippocampal neuronal precursors against the deleterious effect of prolonged sleep loss.
Instituto de Ciencias de la Salud, Departamento de Biomedicina, Universidad Veracruzana, Col. Industrial-Animas, Xalapa, Veracruz, México, C.P., Mexico. fgarcia@uv.mx
Fabio
F
García-García
Alberto K
AK
De la Herrán-Arita
Enrique
E
Juárez-Aguilar
Citlalli
C
Regalado-Santiago
Diana
D
Millán-Aldaco
Carlos
C
Blanco-Centurión
René
R
Drucker-Colín
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D019382:Human Growth Hormone / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000473:pathology* / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000502:physiology; D012892:Sleep Deprivation / Q000150:complications / Q000473:pathology*
D018696:Neuroprotective Agents; D011993:Recombinant Fusion Proteins; D019382:Human Growth Hormone