Growth Hormone Increases BDNF and mTOR Expression in Specific Brain Regions after Photothrombotic Stroke in Mice

Sanchez-Bezanilla, Sonia and Beard, Daniel J. and Hood, Rebecca J. and Aberg, N. David and Crock, Patricia and Walker, Frederick R. and Nilsson, Michael and Isgaard, Jorgen and Ong, Lin Kooi ORCID: https://orcid.org/0000-0001-8664-0540 (2022) Growth Hormone Increases BDNF and mTOR Expression in Specific Brain Regions after Photothrombotic Stroke in Mice. Neural Plasticity, 2022:9983042. pp. 1-13. ISSN 2090-5904

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Abstract

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 μl/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.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Faculty/School / Institute/Centre: No Faculty
Faculty/School / Institute/Centre: No Faculty
Date Deposited: 09 Jun 2022 23:01
Last Modified: 09 Jun 2022 23:01
Uncontrolled Keywords: Animals; Brain; Brain-Derived Neurotrophic Factor; Growth Hormone; Human Growth Hormone; Infarction; Mammals; Mice; Ribosomal Protein S6 Kinases, 70-kDa; Stroke; TOR Serine-Threonine Kinases
Fields of Research (2020): 32 BIOMEDICAL AND CLINICAL SCIENCES > 3214 Pharmacology and pharmaceutical sciences > 321402 Clinical pharmacology and therapeutics
32 BIOMEDICAL AND CLINICAL SCIENCES > 3209 Neurosciences > 320902 Cellular nervous system
32 BIOMEDICAL AND CLINICAL SCIENCES > 3209 Neurosciences > 320999 Neurosciences not elsewhere classified
Socio-Economic Objectives (2020): 20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions
Identification Number or DOI: https://doi.org/10.1155/2022/9983042
URI: http://eprints.usq.edu.au/id/eprint/48227

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