Different modes of GH administration influence gene expression in the male rat brain

Walser, Marion; Schiöler, Linus; Oscarsson, Jan; Åberg, Maria; Svensson, Johan; Åberg, N. David; Isgaard, Jörgen

doi:10.1530/joe-14-0223

Cited by 12 publications

(15 citation statements)

References 57 publications

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“…A mixed model analysis (MMA) was used for all other statistical comparisons, such as to evaluate effects of GHi and GHx2 related to each of the categories of transcripts. For further information on the MMA, Supplementary 233:2 information (Walser et al 2014). P < 0.05 were considered statistically significant.…”

Section: Discussionmentioning

confidence: 99%

“…Detailed information and references on the transcripts are found in Table 2. For information on the calculations of the Q-RT-PCR, Supplementary information (Walser et al 2014).…”

Section: Quantitative Reverse Transcription Polymerase Chain Reactionmentioning

confidence: 99%

“…In rats, the pulsatile mode of GH treatment, which imitates the male endogenous GH secretion (Jansson et al 1982), enhanced Igf1 mRNA levels more than infusions both in rib growth plate and in skeletal muscle (Isgaard et al 1988). So far, the effects of different modes of GH administration have only been investigated in the hippocampus and in the parietal cortex of male hypophysectomised rats (Walser et al 2014). Specifically, we found that the two brain regions are diversely regulated by different modes of GH administration to a moderate extent with the exception for the highly regulated neuronal-haemoglobin beta (Hbb).…”

Section: Introductionmentioning

confidence: 99%

“…injections or as infusions by osmotic minipumps, and investigated the effects on previously known transcripts related to plasticity and transcripts related to oxygenation in the hippocampus and parietal cortex (henceforth cortex). The transcripts were divided into four categories (Walser et al 2014): GH-, neuron-, glia-related and neuron-Hbb (Table 1 and Supplementary Table 1 for further details, see section on supplementary data given at the end of this article). Three transcripts, which have not been studied before, were also measured as they are functionally associated with Hbb and oxygenation (Walser et al 2014).…”

Section: Introductionmentioning

confidence: 99%

“…The transcripts were divided into four categories (Walser et al 2014): GH-, neuron-, glia-related and neuron-Hbb (Table 1 and Supplementary Table 1 for further details, see section on supplementary data given at the end of this article). Three transcripts, which have not been studied before, were also measured as they are functionally associated with Hbb and oxygenation (Walser et al 2014). These were the rate-limiting enzymes of the haeme synthesis delta-aminolevulinate synthase 1 and 2 (Alas1, Alas2) and the hypoxia-inducible factor 1-alpha (HIF1a), which functions as a master transcriptional regulator of the adaptive response to hypoxia (Table 1, for further details see Supplementary Table 1).…”

Section: Introductionmentioning

confidence: 99%

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Mode of GH administration and gene expression in the female rat brain

Walser

Schiöler

Oscarsson

et al. 2017

Journal of Endocrinology

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The endogenous secretion of growth hormone (GH) is sexually dimorphic in rats with females having a more even and males a more pulsatile secretion and low trough levels. The mode of GH administration, mimicking the sexually dimorphic secretion, has different systemic effects. In the brains of male rats, we have previously found that the mode of GH administration differently affects neuron-haemoglobin beta () expression whereas effects on other transcripts were moderate. The different modes of GH administration could have different effects on brain transcripts in female rats. Hypophysectomised female rats were given GH either as injections twice daily or as continuous infusion and GH-responsive transcripts were assessed by quantitative reverse transcription polymerase chain reaction in the hippocampus and parietal cortex (cortex). The different modes of GH-administration markedly increased and 5'-aminolevulinate synthase 2 () in both brain regions. As other effects were relatively moderate, a mixed model analysis (MMA) was used to investigate general effects of the treatments. In the hippocampus, MMA showed that GH-infusion suppressed glia- and neuron-related transcript expression levels, whereas GH-injections increased expression levels. In the cortex, GH-infusion instead increased neuron-related transcripts, whereas GH-injections had no significant effect. Interestingly, this contrasts to previous results obtained from male rat cortex where GH-infusion generally decreased expression levels. In conclusion, the results indicate that there is a small but significant difference in response to mode of GH administration in the hippocampus as compared to the cortex. For both modes of GH administration, there was a robust effect on and.

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Section: Discussionmentioning

confidence: 99%

“…Detailed information and references on the transcripts are found in Table 2. For information on the calculations of the Q-RT-PCR, Supplementary information (Walser et al 2014).…”

Section: Quantitative Reverse Transcription Polymerase Chain Reactionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mode of GH administration and gene expression in the female rat brain

Walser

Schiöler

Oscarsson

et al. 2017

Journal of Endocrinology

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Hemoglobins as new players in multiple sclerosis: metabolic and immune aspects

et al. 2016

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Basic science investigations and clinical observations in recent years indicate that hemoglobins (Hbs) may have important roles in the pathogenesis of multiple sclerosis (MS). These findings can be summarized as follows: 1- Erythrocyte fragility is higher in MS patients, the released free Hb damages blood-brain barrier, myelin basic protein and also triggers iron overload and inflammation. 2- Free Hb may further activate the inflammatory responses through Toll-like receptor 4 (TLR4), present on microglia and other innate immunocytes. 3- Hbs are expressed in neural cells including dopaminergic neurons. Also, several studies have demonstrated that Hbs are expressed in astrocytes and oligodendroglia. 4- Hb overexpression in neural cells upregulate mitochondrial complex I-V subunits. The comparison of the mitochondrial proteome between healthy and patients with MS revealed only four differentially expressed proteins including Hb β-chain. 5- Microarray analysis of 8300 genes in monocytes of twins with and without MS showed a difference in 25 genes that include genes encoding α- and β-globins as well. 6- β- and α-globin gene clusters reside at chromosomal regions 11p15.5 and 16p13.3, respectively. Whole genome screen (WGS) in Sardinian MS families using 327 markers revealed linkage in 3 regions including 11p15.5 loci. Further, 11p15.5 and 16p13.3 were part of the 17 regions identified in the WGS study of 136 sibling-pairs in Nordic countries analyzing 399 microsatellite markers. In the light of these findings, we propose that free Hb released from dying erythrocytes is detrimental. On the contrary, intracellular Hbs in neural cells are protective in MS. The genomic linkage findings can be explained by common haematologically-silent Hb variants that may lower the protective function of intracellular Hbs, and therefore, enhance the risk for MS. In the absence of such variants, aberrations in the translational and post-translational mechanisms controlling synthesis of neural Hbs may also enhance the vulnerability to MS. Alternatively, such genetic variants may perturb the metabolism of anti-inflammatory hemorphins produced via cleavage of Hbs.

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