PMID- 35465399 OWN - NLM STAT- MEDLINE DCOM- 20220426 LR - 20220716 IS - 1687-5443 (Electronic) IS - 2090-5904 (Print) IS - 1687-5443 (Linking) VI - 2022 DP - 2022 TI - Growth Hormone Increases BDNF and mTOR Expression in Specific Brain Regions after Photothrombotic Stroke in Mice. PG - 9983042 LID - 10.1155/2022/9983042 [doi] LID - 9983042 AB - AIMS: We have shown that growth hormone (GH) treatment poststroke increases neuroplasticity in peri-infarct areas and the hippocampus, improving motor and cognitive outcomes. We aimed to explore the mechanisms of GH treatment by investigating how GH modulates pathways known to induce neuroplasticity, focusing on association between brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR) in the peri-infarct area, hippocampus, and thalamus. METHODS: Recombinant human growth hormone (r-hGH) or saline was delivered (0.25 mul/hr, 0.04 mg/day) to mice for 28 days, commencing 48 hours after photothrombotic stroke. Protein levels of pro-BDNF, total-mTOR, phosphorylated-mTOR, total-p70S6K, and phosporylated-p70S6K within the peri-infarct area, hippocampus, and thalamus were evaluated by western blotting at 30 days poststroke. RESULTS: r-hGH treatment significantly increased pro-BDNF in peri-infarct area, hippocampus, and thalamus (p < 0.01). r-hGH treatment significantly increased expression levels of total-mTOR in the peri-infarct area and thalamus (p < 0.05). r-hGH treatment significantly increased expression of total-p70S6K in the hippocampus (p < 0.05). CONCLUSION: r-hGH increases pro-BDNF within the peri-infarct area and regions that are known to experience secondary neurodegeneration after stroke. Upregulation of total-mTOR protein expression in the peri-infarct and thalamus suggests that this might be a pathway that is involved in the neurorestorative effects previously reported in these animals and warrants further investigation. These findings suggest region-specific mechanisms of action of GH treatment and provide further understanding for how GH treatment promotes neurorestorative effects after stroke. CI - Copyright (c) 2022 Sonia Sanchez-Bezanilla et al. FAU - Sanchez-Bezanilla, Sonia AU - Sanchez-Bezanilla S AD - School of Biomedical Sciences and Pharmacy and the Priority Research Centre for Stroke and Brain Injury, The University of Newcastle, NSW, Australia. AD - Hunter Medical Research Institute, NSW, Australia. FAU - Beard, Daniel J AU - Beard DJ AD - School of Biomedical Sciences and Pharmacy and the Priority Research Centre for Stroke and Brain Injury, The University of Newcastle, NSW, Australia. AD - Hunter Medical Research Institute, NSW, Australia. FAU - Hood, Rebecca J AU - Hood RJ AD - School of Biomedical Sciences and Pharmacy and the Priority Research Centre for Stroke and Brain Injury, The University of Newcastle, NSW, Australia. AD - Hunter Medical Research Institute, NSW, Australia. FAU - Aberg, N David AU - Aberg ND AD - Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. AD - Department of Acute Medicine and Geriatrics, Region Vastra Gotaland, Sahlgrenska University Hospital, Gothenburg, Sweden. FAU - Crock, Patricia AU - Crock P AD - Hunter Medical Research Institute, NSW, Australia. AD - Department of Paediatric Endocrinology and Diabetes, John Hunter Children's Hospital, NSW, Australia. FAU - Walker, Frederick R AU - Walker FR AD - School of Biomedical Sciences and Pharmacy and the Priority Research Centre for Stroke and Brain Injury, The University of Newcastle, NSW, Australia. AD - Hunter Medical Research Institute, NSW, Australia. AD - NHMRC Centre of Research Excellence Stroke Rehabilitation and Brain Recovery, VIC, Australia. AD - Centre for Rehab Innovations, The University of Newcastle, NSW, Australia. FAU - Nilsson, Michael AU - Nilsson M AD - School of Biomedical Sciences and Pharmacy and the Priority Research Centre for Stroke and Brain Injury, The University of Newcastle, NSW, Australia. AD - Hunter Medical Research Institute, NSW, Australia. AD - NHMRC Centre of Research Excellence Stroke Rehabilitation and Brain Recovery, VIC, Australia. AD - Centre for Rehab Innovations, The University of Newcastle, NSW, Australia. AD - LKC School of Medicine, Nanyang Technological University, Singapore. FAU - Isgaard, Jorgen AU - Isgaard J AUID- ORCID: 0000-0002-8445-6923 AD - School of Biomedical Sciences and Pharmacy and the Priority Research Centre for Stroke and Brain Injury, The University of Newcastle, NSW, Australia. AD - Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. AD - Department of Specialist Medicine, Region Vastra Gotaland, Sahlgrenska University Hospital, Gothenburg, Sweden. FAU - Ong, Lin Kooi AU - Ong LK AUID- ORCID: 0000-0001-8664-0540 AD - School of Biomedical Sciences and Pharmacy and the Priority Research Centre for Stroke and Brain Injury, The University of Newcastle, NSW, Australia. AD - Hunter Medical Research Institute, NSW, Australia. AD - NHMRC Centre of Research Excellence Stroke Rehabilitation and Brain Recovery, VIC, Australia. AD - School of Pharmacy, Monash University Malaysia, Selangor, Malaysia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220415 PL - United States TA - Neural Plast JT - Neural plasticity JID - 100883417 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 12629-01-5 (Human Growth Hormone) RN - 9002-72-6 (Growth Hormone) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Brain/metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - Growth Hormone MH - *Human Growth Hormone/metabolism MH - Infarction/metabolism MH - Mammals MH - Mice MH - Ribosomal Protein S6 Kinases, 70-kDa/metabolism MH - *Stroke/drug therapy/metabolism MH - TOR Serine-Threonine Kinases/metabolism PMC - PMC9033347 COIS- The authors declare no conflict of interest. EDAT- 2022/04/26 06:00 MHDA- 2022/04/27 06:00 PMCR- 2022/04/15 CRDT- 2022/04/25 05:50 PHST- 2021/10/30 00:00 [received] PHST- 2022/02/10 00:00 [revised] PHST- 2022/03/08 00:00 [accepted] PHST- 2022/04/25 05:50 [entrez] PHST- 2022/04/26 06:00 [pubmed] PHST- 2022/04/27 06:00 [medline] PHST- 2022/04/15 00:00 [pmc-release] AID - 10.1155/2022/9983042 [doi] PST - epublish SO - Neural Plast. 2022 Apr 15;2022:9983042. doi: 10.1155/2022/9983042. eCollection 2022.