Growth hormone increases dendritic spine density in primary hippocampal cell cultures

Nylander, Erik; Zelleroth, Sofia; Stam, Frida; Nyberg, Fred; Grönbladh, Alfhild; Hallberg, Mathias

doi:10.1016/j.ghir.2019.12.003

Cited by 7 publications

(7 citation statements)

References 38 publications

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“…However, in contrast to some earlier reported data 6 their studies on the effects of hyper‐secretion of the actual hormones on neurogenesis no increase in the number of newly generated neurons was seen. This is also in contrast to our recent observation that high concentrations of GH may stimulate neurite outgrowth in rat hippocampal cells 7 . On the other hand, after applying additional approaches for their investigation on neurogenesis Martin‐Rodriguez and co‐workers noted that hyper‐secretion of GH and IGF‐I might cause a premature acceleration of early progenitors to promote neuronal differentiation 4 .…”

contrasting

confidence: 86%

Growing knowledge: How growth hormone improves learning

Nyberg

Hallberg

2020

Acta Physiologica

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contrasting

confidence: 86%

Growing knowledge: How growth hormone improves learning

Nyberg

Hallberg

2020

Acta Physiologica

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“…In addition to its classical actions on growth and metabolism, growth hormone (GH) has been reported to play a relevant role, as a neurotrophic factor, on brain repair after traumatic brain injury (TBI) and stroke [4][5][6]. The neurotrophic actions of GH in the central nervous system (CNS) include prosurvival effects during embryonic development [7,8], neurogenesis in the adult brain [9], structural plasticity [10,11], and synaptogenesis [12], among others. These effects could be associated with the cognitive and motor improvement observed in TBI patients, with or without growth hormone deficiency (GHD), who received GH therapy [6,[13][14][15].…”

Section: Introductionmentioning

confidence: 99%

“…Neural Plasticity such as a reduction of neurite number and length. Beneficial effects of GH treatment upon structural and synaptic plasticity have been reported, either by increasing the dendritic length and number of dendritic spines in the cortex and hippocampus of the rat [10,11], by regulating the expression of α-amino-3-hydroxyl-5-methyl-4-isoxazol-propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors, or by increasing the expression of postsynaptic density 95 protein [85]. Here, we demonstrated that GH treatment improved structural and synaptic plasticity in the injured hippocampal cell cultures.…”

mentioning

confidence: 99%

Growth Hormone (GH) Enhances Endogenous Mechanisms of Neuroprotection and Neuroplasticity after Oxygen and Glucose Deprivation Injury (OGD) and Reoxygenation (OGD/R) in Chicken Hippocampal Cell Cultures

et al. 2021

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As a classical growth promoter and metabolic regulator, growth hormone (GH) is involved in development of the central nervous system (CNS). This hormone might also act as a neurotrophin, since GH is able to induce neuroprotection, neurite growth, and synaptogenesis during the repair process that occurs in response to neural injury. After an ischemic insult, the neural tissue activates endogenous neuroprotective mechanisms regulated by local neurotrophins that promote tissue recovery. In this work, we investigated the neuroprotective effects of GH in cultured hippocampal neurons exposed to hypoxia-ischemia injury and further reoxygenation. Hippocampal cell cultures obtained from chick embryos were incubated under oxygen-glucose deprivation (OGD, <5% O2, 1 g/L glucose) conditions for 24 h and simultaneously treated with GH. Then, cells were either collected for analysis or submitted to reoxygenation and normal glucose incubation conditions (OGD/R) for another 24 h, in the presence of GH. Results showed that OGD injury significantly reduced cell survival, the number of cells, dendritic length, and number of neurites, whereas OGD/R stage restored most of those adverse effects. Also, OGD/R increased the mRNA expression of several synaptogenic markers (i.e., NRXN1, NRXN3, NLG1, and GAP43), as well as the growth hormone receptor (GHR). The expression of BDNF, IGF-1, and BMP4 mRNAs was augmented in response to OGD injury, and exposure to OGD/R returned it to normoxic control levels, while the expression of NT-3 increased in both conditions. The addition of GH (10 nM) to hippocampal cultures during OGD reduced apoptosis and induced a significant increase in cell survival, number of cells, and doublecortin immunoreactivity (DCX-IR), above that observed in the OGD/R stage. GH treatment also protected dendrites and neurites during OGD, inducing plastic changes reflected in an increase and complexity of their outgrowths during OGD/R. Furthermore, GH increased the expression of NRXN1, NRXN3, NLG1, and GAP43 after OGD injury. GH also increased the BDNF expression after OGD, but reduced it after OGD/R. Conversely, BMP4 was upregulated by GH after OGD/R. Overall, these results indicate that GH protective actions in the neural tissue may be explained by a synergic combination between its own effect and that of other local neurotrophins regulated by autocrine/paracrine mechanisms, which together accelerate the recovery of tissue damaged by hypoxia-ischemia.

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“…However, region-, cell-type-, and age-specific rhGH effects on the neurovascular unit have to be considered and remain to be clarified in detail. Altogether, rhGH treatment might create the opportunity to combine regeneration of the neurovascular unit by activation of the endogenous vascular–regenerative growth factors VEGF, EPO, and IGF-1 and neuroprotection [ 48 , 51 ] in hypoxic developing brain injury.…”

Section: Discussionmentioning

confidence: 99%

“…We assessed safety and efficacy in the range of 1000–4000 µg/kg body weight in our previous in vivo study, where a high-dose treatment did not affect hematocrit and hemoglobin levels or body weight development [ 6 ]. Drug toxicity was excluded in vitro by our previous studies on primary mouse cortical neurons (E14 and DIV6; Jung et al, 2021) and comprehensive observations from literature, including the use of supraphysiological doses of rhGH [ 27 , 51 ].…”

Section: Methodsmentioning

confidence: 99%

Further Evidence of Neuroprotective Effects of Recombinant Human Erythropoietin and Growth Hormone in Hypoxic Brain Injury in Neonatal Mice

Klepper

Jung

Dittmann

et al. 2022

IJMS

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Experimental in vivo data have recently shown complementary neuroprotective actions of rhEPO and growth hormone (rhGH) in a neonatal murine model of hypoxic brain injury. Here, we hypothesized that rhGH and rhEPO mediate stabilization of the blood–brain barrier (BBB) and regenerative vascular effects in hypoxic injury to the developing brain. Using an established model of neonatal hypoxia, neonatal mice (P7) were treated i.p. with rhGH (4000 µg/kg) or rhEPO (5000 IU/kg) 0/12/24 h after hypoxic exposure. After a regeneration period of 48 h or 7 d, cerebral mRNA expression of Vegf-A, its receptors and co-receptors, and selected tight junction proteins were determined using qRT-PCR and ELISA. Vessel structures were assessed by Pecam-1 and occludin (Ocln) IHC. While Vegf-A expression increased significantly with rhGH treatment (p < 0.01), expression of the Vegfr and TEK receptor tyrosine kinase (Tie-2) system remained unchanged. RhEPO increased Vegf-A (p < 0.05) and Angpt-2 (p < 0.05) expression. While hypoxia reduced the mean vessel area in the parietal cortex compared to controls (p < 0.05), rhGH and rhEPO prevented this reduction after 48 h of regeneration. Hypoxia significantly reduced the Ocln+ fraction of cortical vascular endothelial cells. Ocln signal intensity increased in the cortex in response to rhGH (p < 0.05) and in the cortex and hippocampus in response to rhEPO (p < 0.05). Our data indicate that rhGH and rhEPO have protective effects on hypoxia-induced BBB disruption and regenerative vascular effects during the post-hypoxic period in the developing brain.

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Growth hormone increases dendritic spine density in primary hippocampal cell cultures

Cited by 7 publications

References 38 publications

Growing knowledge: How growth hormone improves learning

Growing knowledge: How growth hormone improves learning

Growth Hormone (GH) Enhances Endogenous Mechanisms of Neuroprotection and Neuroplasticity after Oxygen and Glucose Deprivation Injury (OGD) and Reoxygenation (OGD/R) in Chicken Hippocampal Cell Cultures

Further Evidence of Neuroprotective Effects of Recombinant Human Erythropoietin and Growth Hormone in Hypoxic Brain Injury in Neonatal Mice

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