Metabolic insights from a GHSR-A203E mutant mouse model.
Javier
September 20, 2020
Ghrelin binding to its receptor, growth hormone secretagogue receptor (GHSR) stimulates GH release, induce eating, and increase blood glucose. This process can also be influenced by the constitutive activity of GHSR (ghrelin-independent), as suggested by the findings of short stature in people with naturally occurring mutations GHSR-A204E and reduces food intake and blood glucose in rats given GHSR inverse agonists both harmful GHSR constitutive activity.
Here, we aim to further define the physiological relevance of constitutive GHSR activity.We GHSR generated mice with the mutation that replaces alanine at position 203 with glutamate (GHSR-A203E), in accordance with the A204E mutation-human GHSR above-referenced, and using them to perform ex vivo neuronal electrophysiology and in vivo assessment of metabolism. Also, we measure the signal in COS-7 and HEK293T cells transfected with wild-type GHSR (GHSR-WT) or construction GHSR-A203E.
RESULTS
In COS-7 cells, GHSR-A203E IP3 accumulation resulting lower base than GHSR-WT; ghrelin induced IP3 accumulation was observed for both construction. In HEK293T cells co-transfected with the voltage-gated CaVVVOur the data indicate that the A203E mutation ablates GHSR constitutive activity and constitutive activity GHSR original contribution to the conductance depolarizing GHSR-express NPY curve.
Although the A203E mutation does not block the ghrelin-generates a signal that is assessed using in vitro and ex vivo models, rat-A203E GHSR acute food shortages typically respond to ghrelin intake given in vivo. Also, GHSR-A203E mutation blunts GH release, and, in aged mice, leading to a decrease in body length and femur length, which is consistent with short stature human carrier GHSR-A204E mutation.
Metabolic insights from a GHSR-A203E mutant mouse model.
Effects of Alcohol and cocaine in Mutant Rat Model predisposition Post-Traumatic Stress Disorder
Comorbidity between substance abuse and post-traumatic stress disorder (PTSD), a stress-related dysregulation of fear responses, very high. While some drugs known to increase fear and anxiety, there are few data regarding the interaction between voluntary consumption of drugs and the fear memory.
Either spontaneous chronic consumption of alcohol or cocaine under 3 weeks of free choice progressive paradigm alcohol (3/6/10%) or cocaine (0.2 / 0.4 / 0.6 mg / ml), assessed in VGV transgenic mice, have full 5-HT2C receptor editing and displaying PTSD-like behaviors. The consequences of the consumption of these drugs on the potential contextual and cued fear conditioning response of VGV mice was assessed. Drug effects on hippocampal neurotrophic factor derived from the brain (BDNF) mRNA expression was measured as previously was found to decrease in VGV mice.
Chronic alcohol consumption was similar in WT and VGV mice. Under conditions of alcohol, the acquisition of fear is no different at the end of the learning session and cue-facilitated fear extinction. Regarding cocaine, in contrast to WT mice, rats VGV not improve their drug consumption along with increased dosage, effects that may be associated with stimulation of discrimination was increased through an increase in 5-HT2C receptor.
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10Tests
EUR 570
Tissue cDNA, First Strand, Human Tumor, Bladder, BioGenomics
MBS652153-5x10Tests
MyBiosource
5x10Tests
EUR 2345
Tissue cDNA, First Strand, Canine Adult Normal, Liver, BioGenomics
MBS652364-40Tests
MyBiosource
40Tests
EUR 680
Tissue cDNA, First Strand, Canine Adult Normal, Liver, BioGenomics
MBS652364-5x40Tests
MyBiosource
5x40Tests
EUR 2835
Tissue cDNA, First Strand, Canine Adult Normal, Heart, BioGenomics
MBS652465-40Tests
MyBiosource
40Tests
EUR 680
Tissue cDNA, First Strand, Canine Adult Normal, Heart, BioGenomics
MBS652465-5x40Tests
MyBiosource
5x40Tests
EUR 2835
Tissue cDNA, First Strand, Mouse Adult Normal, Spleen, BioGenomics
MBS652480-40Tests
MyBiosource
40Tests
EUR 680
Tissue cDNA, First Strand, Mouse Adult Normal, Spleen, BioGenomics
MBS652480-5x40Tests
MyBiosource
5x40Tests
EUR 2835
Tissue cDNA, First Strand, Mouse Adult Normal, Kidney, BioGenomics
MBS652496-40Tests
MyBiosource
40Tests
EUR 680
Cocaine-intake VGV mice do not display contextual generalization fear VGV usually observed in control rats. In addition, BDNF expression was upregulated after alcohol intake or chronic cocaine either. Overall, these results indicate that both chronic alcohol and cocaine consumption may exert some voluntary oral therapeutic effect in models like the mutants PTSD predisposition.