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

Article

Sanchez-Bezanilla, Sonia, Beard, Daniel J., Hood, Rebecca J., Aberg, N. David, Crock, Patricia, Walker, Frederick R., Nilsson, Michael, Isgaard, Jorgen and Ong, Lin Kooi. 2022. "Growth Hormone Increases BDNF and mTOR Expression in Specific Brain Regions after Photothrombotic Stroke in Mice." Neural Plasticity. 2022, pp. 1-13. https://doi.org/10.1155/2022/9983042
Article Title

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

ERA Journal ID211137
Article CategoryArticle
AuthorsSanchez-Bezanilla, Sonia (Author), Beard, Daniel J. (Author), Hood, Rebecca J. (Author), Aberg, N. David (Author), Crock, Patricia (Author), Walker, Frederick R. (Author), Nilsson, Michael (Author), Isgaard, Jorgen (Author) and Ong, Lin Kooi (Author)
Journal TitleNeural Plasticity
Journal Citation2022, pp. 1-13
Article Number9983042
Number of Pages13
Year2022
Place of PublicationUnited Kingdom
ISSN1687-5443
2090-5904
Digital Object Identifier (DOI)https://doi.org/10.1155/2022/9983042
Web Address (URL)https://www.hindawi.com/journals/np/2022/9983042/
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.

KeywordsAnimals; Brain; Brain-Derived Neurotrophic Factor; Growth Hormone; Human Growth Hormone; Infarction; Mammals; Mice; Ribosomal Protein S6 Kinases, 70-kDa; Stroke; TOR Serine-Threonine Kinases
ANZSRC Field of Research 2020321402. Clinical pharmacology and therapeutics
320902. Cellular nervous system
320999. Neurosciences not elsewhere classified
Byline AffiliationsUniversity of Newcastle
University of Gothenburg, Sweden
Hunter Medical Research Institute, Australia
Institution of OriginUniversity of Southern Queensland
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The role of inflammation and dopamine synthesis in Parkinson's disease
Ong, L. K., Briggs, G. D., Dunkley, P. R. and Dickson, P. W.. 2014. "The role of inflammation and dopamine synthesis in Parkinson's disease." 12th Biennial Meeting of the Asian-Pacific-Society-for-Neurochemistry (2014). Taiwan 23 - 26 Aug 2014 United Kingdom.
mTORC1 Inhibition in the Nucleus Accumbens ‘Protects’ Against the Expression of Drug Seeking and ‘Relapse’ and Is Associated with Reductions in GluA1 AMPAR and CAMKIIa Levels
James, Morgan H., Quinn, Rikki K., Ong, Lin Kooi, Levi, Emily M., Charnley, Janine L., Smith, Doug W., Dickson, Phillip W. and Dayas, Christopher V.. 2014. "mTORC1 Inhibition in the Nucleus Accumbens ‘Protects’ Against the Expression of Drug Seeking and ‘Relapse’ and Is Associated with Reductions in GluA1 AMPAR and CAMKIIa Levels." Neuropsychopharmacology. 39 (7), pp. 1694-1702. https://doi.org/10.1038/npp.2014.16
Neurobiological consequences of acute footshock stress: effects on tyrosine hydroxylase phosphorylation and activation in the rat brain and adrenal medulla
Ong, Lin Kooi, Guan, Liying, Damanhuri, Hanafi, Goodchild, Ann K., Bobrovskaya, Larisa, Dickson, Phillip W. and Dunkley, Peter R.. 2014. "Neurobiological consequences of acute footshock stress: effects on tyrosine hydroxylase phosphorylation and activation in the rat brain and adrenal medulla." Journal of Neurochemistry. 128 (4), pp. 547-560. https://doi.org/10.1111/jnc.12482
Early Life Stress and Post-Weaning High Fat Diet Alter Tyrosine Hydroxylase Regulation and AT1 Receptor Expression in the Adrenal Gland in a Sex Dependent Manner
Bobrovskaya, Larisa, Maniam, Jayanthi, Ong, Lin Kooi, Dunkley, Peter R. and Morris, Margaret J.. 2013. "Early Life Stress and Post-Weaning High Fat Diet Alter Tyrosine Hydroxylase Regulation and AT1 Receptor Expression in the Adrenal Gland in a Sex Dependent Manner." Neurochemical Research. 38 (4), pp. 826-833. https://doi.org/10.1007/s11064-013-0985-4
Functional Programming of the Autonomic Nervous System by Early Life Immune Exposure: Implications for Anxiety
Sominsky, Luba, Fuller, Erin A., Bondarenko, Evgeny, Ong, Lin Kooi, Averell, Lee, Nalivaiko, Eugene, Dunkley, Peter R., Dickson, Phillip W. and Hodgson, Deborah M.. 2013. "Functional Programming of the Autonomic Nervous System by Early Life Immune Exposure: Implications for Anxiety." PLoS One. 8 (3), pp. 1-13. https://doi.org/10.1371/journal.pone.0057700
Tyrosine Hydroxylase Phosphorylation in Catecholaminergic Brain Regions: A Marker of Activation following Acute Hypotension and Glucoprivation
Damanhuri, Hanafi A., Burke, Peter G. R., Ong, Lin K., Bobrovskaya, Larisa, Dickson, Phillip W., Dunkley, Peter R. and Goodchild, Ann K.. 2012. "Tyrosine Hydroxylase Phosphorylation in Catecholaminergic Brain Regions: A Marker of Activation following Acute Hypotension and Glucoprivation." PLoS One. 7 (11), pp. 1-19. https://doi.org/10.1371/journal.pone.0050535
The Sustained Phase of Tyrosine Hydroxylase Activation In vivo
Ong, Lin Kooi, Sominsky, Luba, Dickson, Phillip W., Hodgson, Deborah M. and Dunkley, Peter R.. 2012. "The Sustained Phase of Tyrosine Hydroxylase Activation In vivo." Neurochemical Research. 37 (9), pp. 1938-1943. https://doi.org/10.1007/s11064-012-0812-3
Increased microglial activation in the rat brain following neonatal exposure to a bacterial mimetic
Sominsky, L., Walker, A. K., Ong, L. K., Tynan, R. J., Walker, F. R. and Hodgson, D. M.. 2012. "Increased microglial activation in the rat brain following neonatal exposure to a bacterial mimetic." Behavioural Brain Research. 226 (1), pp. 351-356. https://doi.org/10.1016/j.bbr.2011.08.038
The effects of footshock and immobilization stress on tyrosine hydroxylase phosphorylation in the rat locus coeruleus and adrenal gland
Ong, L. K., Guan, L., Stutz, B., Dickson, P. W., Dunkley, P. R. and Bobrovskaya, L.. 2011. "The effects of footshock and immobilization stress on tyrosine hydroxylase phosphorylation in the rat locus coeruleus and adrenal gland." Neuroscience. 192, pp. 20-27. https://doi.org/10.1016/j.neuroscience.2011.06.087
Epigenetic Inheritance of Anxiety-Like Behaviour in Rats - Role of Early Life Exposure to a Bacterial Mimetic
Sominsky, L., Walker, A. K., Ong, L., Tynan, R. J., Walker, F. R. and Hodgson, D. M.. 2011. "Epigenetic Inheritance of Anxiety-Like Behaviour in Rats - Role of Early Life Exposure to a Bacterial Mimetic." Journal of Developmental Origins of Health and Disease. 2, pp. S109-S109.
Neonatal respiratory infection and adult re-infection: Effect on glucocorticoid and mineralocorticoid receptors in the hippocampus in BALB/c mice
Wynne, O., Horvat, J. C., Kim, R. Y., Ong, L. K., Smith, R., Hansbro, P. M., Clifton, V. L. and Hodgson, D. M.. 2011. "Neonatal respiratory infection and adult re-infection: Effect on glucocorticoid and mineralocorticoid receptors in the hippocampus in BALB/c mice." Brain, Behavior, and Immunity. 25 (6), pp. 1214-1222. https://doi.org/10.1016/j.bbi.2011.03.014
Sustained Phosphorylation of Tyrosine Hydroxylase at Serine 40 in VIVO
Ong, L. K., Sominsky, L., Walker, A. K., Hodgson, D. M., Goodchild, A. K., Bobrovskaya, L., Dickson, P. W. and Dunkley, P. R.. 2011. "Sustained Phosphorylation of Tyrosine Hydroxylase at Serine 40 in VIVO." 23rd Biennial Meeting of the International Society for Neurochemistry (2011). Athen, Greece 28 Aug - 01 Sep 2011 United Kingdom.
The Effect of Social Defeat on Tyrosine Hydroxylase Phosphorylation in the Rat Brain and Adrenal Gland
Ong, Lin Kooi, Bobrovskaya, Larisa, Walker, Frederick R., Day, Trevor A., Dickson, Phillip W. and Dunkley, Peter R.. 2011. "The Effect of Social Defeat on Tyrosine Hydroxylase Phosphorylation in the Rat Brain and Adrenal Gland." Neurochemical Research. 36 (1), pp. 27-33. https://doi.org/10.1007/s11064-010-0255-7
Tyrosine hydroxylase phosphorylation in response to footshock and restraint stress
Ong, L., Guan, L., Stutz, B., Dickson, P., Dunkley, P. and Bobrovskaya, L.. 2010. "Tyrosine hydroxylase phosphorylation in response to footshock and restraint stress." Journal of Neurochemistry. 115, pp. 77-77.
Signal transduction pathways and tyrosine hydroxylase regulation in the adrenal medulla following glucoprivation: An in vivo analysis
Bobrovskaya, Larisa, Damanhuri, Hanafi A., Ong, Lin Kooi, Schneider, Jennifer J., Dickson, Phillip W., Dunkley, Peter R. and Goodchild, Ann K.. 2010. "Signal transduction pathways and tyrosine hydroxylase regulation in the adrenal medulla following glucoprivation: An in vivo analysis." Neurochemistry International: the journal for the publication of cellular and molecular aspects of neurochemistry. 57 (2), pp. 162-167. https://doi.org/10.1016/j.neuint.2010.05.009
The effect of social conflict on tyrosine hydroxylase phosphorylation in catecholamine-producing cells from sprague-dawley rats
Ong, L., Bobrovskaya, L., Walker, F., Day, Trevor, Dickson, P. and Dunkley, P.. 2009. "The effect of social conflict on tyrosine hydroxylase phosphorylation in catecholamine-producing cells from sprague-dawley rats." 22nd Biennial Meeting of the International Society for Neurochemistry & Asian Pacific Society for Neurochemistry (2009). South Korea 23 - 29 Aug 2009 United Kingdom.
Cross-neutralisation of Australian brown and tiger snake venoms with commercial antivenoms: Cross-reactivity or antivenom mixtures?
O’Leary, Margaret A., Schneider, Jennifer J., Prakash Krishnan, Brian, Lavis, Christopher, McKendry, Amy, Ong, Lin Kooi and Isbister, Geoffrey K.. 2007. "Cross-neutralisation of Australian brown and tiger snake venoms with commercial antivenoms: Cross-reactivity or antivenom mixtures?" Toxicon. 50 (2), pp. 206-213. https://doi.org/10.1016/j.toxicon.2007.03.014