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- Le Grevès, Madeleine, et al.
(författare)
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Age-related effects of IGF-1 on the NMDA-, GH- and IGF-1 receptor mRNA transcripts in the rat hippocampus
- 2005
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Ingår i: Brain Research Bulletin. - : Elsevier BV. - 0361-9230 .- 1873-2747. ; 65:5, s. 369-374
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-like growth factor-1 (IGF-1) and growth hormone (GH) have been suggested to promote memory and cognitive capabilities. In a recent publication we observed that GH increase the proportion of the NR2B subunit mRNA transcript of the NMDA receptor in rat hippocampus. NR2B has been suggested to be essential for spatial learning and long-term potentiation (LTP). This effect of GH might be IGF-1-mediated or a result of a co-ordination with IGF-1. To test this hypothesis further, we examined the effects of 10 daily s.c. injections of IGF-1 on NMDA receptor subunits (NR1, NR2A, and NR2B), GH receptor (GHR), GH binding protein (GHBP) and type 1 IGF receptor (IGF-1R) gene transcripts in the hippocampus. The NR2B subunit mRNA increased in young (11 weeks) but not in older (14-16 months) rats and the expression of the NR2A mRNA was decreased in both groups. The ratio of NR2B to NR2A is suggested to mirror the potential for synaptic plasticity. In both age groups, IGF-1 treatment resulted in a significant increase of this ratio at transcription level. The GHR mRNA increased in young rats, mimicking the effect of GH, while the IGF-1R mRNA was decreased in the older group of rats after IGF-1 treatment. These results suggest that IGF-1 in many aspects may mediate the actions earlier shown for GH.
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| 6. |
- Rossbach, Uwe, et al.
(författare)
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Acute 19-nortestosterone transiently suppresses hippocampal MAPK pathway and the phosphorylation of the NMDA receptor
- 2010
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Ingår i: Molecular and Cellular Endocrinology. - Ireland : Elsevier. - 0303-7207 .- 1872-8057. ; 314:1, s. 143-149
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Tidskriftsartikel (refereegranskat)abstract
- High doses of anabolic androgenic steroid are associated with changes in personality, e.g. increased aggression and irritability, behavioural changes that may be linked to structural changes in the hippocampus. In this in vivo study we demonstrate acute effects of a single injection of 19-nortestosterone on proteins that play a major role in molecular plasticity at synaptic connections. The steroid rapidly and transiently decreased total and phosphorylated NMDA receptor GluN2B subunit levels and phosphorylated extracellular signal-regulated kinase 1 in rat hippocampal synaptoneurosomes. Pretreatment with the androgen receptor antagonist flutamide prevented these effects suggesting an androgen receptor mediated mode of action. However, flutamide alone stimulated the phosphorylation of both extracellular signal-regulated kinase 1 and 2. EphrinB2 and phosphorylated translation initiation factor 4E, two proteins that act on synaptic plasticity through NMDA receptor and/or mitogen-activated protein kinase pathways, were not affected by any of the treatment regimens. This study demonstrates rapid in vivo effects of an anabolic androgenic steroid on two key elements in hippocampal synaptic plasticity.
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| 8. |
- Benedict, Christian, et al.
(författare)
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Association between physical activity and brain health in older adults
- 2013
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:1, s. 83-90
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Tidskriftsartikel (refereegranskat)abstract
- In the present cross-sectional study, we examined physical activity (PA) and its possible association with cognitive skills and brain structure in 331 cognitively healthy elderly. Based on the number of self-reported light and hard activities for at least 30 minutes per week, participants were assigned to 4 groups representing different levels of PA. The cognitive skills were assessed by the Mini Mental State Examination score, a verbal fluency task, and the Trail-making test as a measure of visuospatial orientation ability. Participants also underwent a magnetic resonance imaging of the brain. Multiple regression analysis revealed that greater PA was associated with a shorter time to complete the Trail-making test, and higher levels of verbal fluency. Further, the level of self-reported PA was positively correlated with brain volume, white matter, as well as a parietal lobe gray matter volume, situated bilaterally at the precuneus. These present cross-sectional results indicate that PA is a lifestyle factor that is linked to brain structure and function in late life.
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| 9. |
- Birgner, Carolina, et al.
(författare)
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VGLUT2 in dopamine neurons is required for psychostimulant-induced behavioural activation
- 2010
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:1, s. 389-394
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Tidskriftsartikel (refereegranskat)abstract
- The “One neuron-one neurotransmitter” concept has been challenged frequently during the last three decades, and the coexistence of neurotransmitters in individual neurons is now regarded as a common phenomenon. The functional significance of neurotransmitter coexistence is, however, less well understood. Several studies have shown that a subpopulation of dopamine (DA) neurons in the ventral tegmental area (VTA) expresses the vesicular glutamate transporter 2 (VGLUT2) and has been suggested to use glutamate as a cotransmitter. The VTA dopamine neurons project to limbic structures including the nucleus accumbens, and are involved in mediating the motivational and locomotor activating effects of psychostimulants. To determine the functional role of glutamate cotransmission by these neurons, we deleted VGLUT2 in DA neurons by using a conditional gene-targeting approach in mice. A DAT-Cre/Vglut2Lox mouse line (Vglut2f/f;DAT-Cre mice) was produced and analyzed by in vivo amperometry as well as by several behavioral paradigms. Although basal motor function was normal in the Vglut2f/f;DAT-Cre mice, their risk-taking behavior was altered. Interestingly, in both home-cage and novel environments, the gene targeted mice showed a greatly blunted locomotor response to the psychostimulant amphetamine, which acts via the midbrain DA system. Our results show that VGLUT2 expression in DA neurons is required for normal emotional reactivity as well as for psychostimulant-mediated behavioral activation.
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| 10. |
- Caruso, Vanni, et al.
(författare)
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The Orphan G Protein-Coupled Receptor Gene GPR178 Is Evolutionary Conserved and Altered in Response to Acute Changes in Food Intake
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- G protein-coupled receptors (GPCRs) are a class of integral membrane proteins mediating physiological functions fundamental for survival, including energy homeostasis. A few years ago, an amino acid sequence of a novel GPCR gene was identified and named GPR178. In this study, we provide new insights regarding the biological significance of Gpr178 protein, investigating its evolutionary history and tissue distribution as well as examining the relationship between its expression level and feeding status. Our phylogenetic analysis indicated that GPR178 is highly conserved among all animal species investigated, and that GPR178 is not a member of a protein family. Real-time PCR and in situ hybridization revealed wide expression of Gpr178 mRNA in both the brain and periphery, with high expression density in the hypothalamus and brainstem, areas involved in the regulation of food intake. Hence, changes in receptor expression were assessed following several feeding paradigms including starvation and overfeeding. Short-term starvation (12-48h) or food restriction resulted in upregulation of Gpr178 mRNA expression in the brainstem, hypothalamus and prefrontal cortex. Conversely, short-term (48h) exposure to sucrose or Intralipid solutions downregulated Gpr178 mRNA in the brainstem; long-term exposure (10 days) to a palatable high-fat and high-sugar diet resulted in a downregulation of Gpr178 in the amygdala but not in the hypothalamus. Our results indicate that hypothalamic Gpr178 gene expression is altered during acute exposure to starvation or acute exposure to palatable food. Changes in gene expression following palatable diet consumption suggest a possible involvement of Gpr178 in the complex mechanisms of feeding reward.
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