scholarly journals Dorsomedial Prefrontal Cortex Mediates the Impact of Serotonin Transporter Linked Polymorphic Region Genotype on Anticipatory Threat Reactions

2015 ◽  
Vol 78 (8) ◽  
pp. 582-589 ◽  
Author(s):  
Floris Klumpers ◽  
Marijn C. Kroes ◽  
Ivo Heitland ◽  
Daphne Everaerd ◽  
Sophie E.A. Akkermans ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Serotonin Transporter ◽  
Polymorphic Region ◽  
Dorsomedial Prefrontal Cortex ◽  
The Impact

scholarly journals Mouse model of the human serotonin transporter-linked polymorphic region

2019 ◽  
Vol 30 (11-12) ◽  
pp. 319-328
Author(s):  
Lukasz Piszczek ◽  
Simone Memoli ◽  
Angelo Raggioli ◽  
José Viosca ◽  
Jeanette Rientjes ◽  
...  
Keyword(s):  
Mouse Model ◽  
Emotional Disorders ◽  
Serotonin Transporter ◽  
Single Copy ◽  
Weight Of Evidence ◽  
Polymorphic Region ◽  
Common Genetic Variants ◽  
Living Mouse ◽  
Technical Issues ◽  
The Impact

AbstractGenetic factors play a significant role in risk for mood and anxiety disorders. Polymorphisms in genes that regulate the brain monoamine systems, such as catabolic enzymes and transporters, are attractive candidates for being risk factors for emotional disorders given the weight of evidence implicating monoamines involvement in these conditions. Several common genetic variants have been identified in the human serotonin transporter (5-HTT) gene, including a repetitive sequence located in the promoter region of the locus called the serotonin transporter-linked polymorphic region (5-HTT-LPR). This polymorphism has been associated with a number of mental traits in both humans and primates, including depression, neuroticism, and harm avoidance. Some, but not all, studies found a link between the polymorphism and 5-HTT levels, leaving open the question of whether the polymorphism affects risk for mental traits via changes in 5-HTT expression. To investigate the impact of the polymorphism on gene expression, serotonin homeostasis, and behavioral traits, we set out to develop a mouse model of the human 5-HTT-LPR. Here we describe the creation and characterization of a set of mouse lines with single-copy human transgenes carrying the short and long 5-HTT-LPR variants. Although we were not able to detect differences in expression between the short and long variants, we encountered several technical issues concerning the design of our humanized mice that are likely to have influenced our findings. Our study serves as a cautionary note for future studies aimed at studying human transgene regulation in the context of the living mouse.

scholarly journals Mouse model of the human serotonin transporter-linked polymorphic region

2019 ◽  
Author(s):  
Lukasz Piszczek ◽  
Simone Memoli ◽  
Angelo Raggioli ◽  
José Viosca ◽  
Jeanette Rientjes ◽  
...  
Keyword(s):  
Mouse Model ◽  
Emotional Disorders ◽  
Serotonin Transporter ◽  
Single Copy ◽  
Weight Of Evidence ◽  
Polymorphic Region ◽  
Common Genetic Variants ◽  
The Impact ◽  
The Brain

AbstractGenetic factors play a significant role in risk for mood and anxiety disorders. Polymorphisms in genes that regulate the brain monoamine systems, such as catabolic enzymes and transporters, are attractive candidates for being risk factors for emotional disorders given the weight of evidence implicating monoamines involvement in these conditions. Several common genetic variants have been identified in the human serotonin transporter (5-HTT) gene, including a repetitive sequence located in the promoter region of the locus called the serotonin transporter-linked polymorphic region (5-HTT-LPR). This polymorphism has been associated with a number of mental traits in both humans and primates, including depression, neuroticism, and harm avoidance. Some, but not all studies found a link between the polymorphism and 5-HTT levels, leaving open the question of whether the polymorphism affects risk for mental traits via changes in 5-HTT expression. To investigate the impact of the polymorphism on gene expression, serotonin homeostasis, and behavioural traits we set out to develop a mouse model of the human 5-HTT- LPR. Here we describe the creation and characterization of a set of mouse lines with single copy human transgenes carrying the short and long 5-HTT-LPR variants.

scholarly journals A 1-Month Ketogenic Diet Increased Mitochondrial Mass in Red Gastrocnemius Muscle, but not in the Brain or Liver of Middle-Aged Mice

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2533
Author(s):  
Zeyu Zhou ◽  
Jocelyn Vidales ◽  
José A González-Reyes ◽  
Bradley Shibata ◽  
Keith Baar ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Gastrocnemius Muscle ◽  
Left Lobe ◽  
Middle Aged ◽  
Mitochondrial Content ◽  
Mitochondrial Mass ◽  
Aged Mice ◽  
Fractional Area ◽  
Ketogenic Diets ◽  
The Impact

Alterations in markers of mitochondrial content with ketogenic diets (KD) have been reported in tissues of rodents, but morphological quantification of mitochondrial mass using transmission electron microscopy (TEM), the gold standard for mitochondrial quantification, is needed to further validate these findings and look at specific regions of interest within a tissue. In this study, red gastrocnemius muscle, the prefrontal cortex, the hippocampus, and the liver left lobe were used to investigate the impact of a 1-month KD on mitochondrial content in healthy middle-aged mice. The results showed that in red gastrocnemius muscle, the fractional area of both subsarcolemmal (SSM) and intermyofibrillar (IMM) mitochondria was increased, and this was driven by an increase in the number of mitochondria. Mitochondrial fractional area or number was not altered in the liver, prefrontal cortex, or hippocampus following 1 month of a KD. These results demonstrate tissue-specific changes in mitochondrial mass with a short-term KD and highlight the need to study different muscle groups or tissue regions with TEM to thoroughly determine the effects of a KD on mitochondrial mass.

scholarly journals A pilot trial of repetitive transcranial magnetic stimulation of the dorsomedial prefrontal cortex in anorexia nervosa: resting fMRI correlates of response

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
D. Blake Woodside ◽  
Katharine Dunlop ◽  
Charlene Sathi ◽  
Eileen Lam ◽  
Brigitte McDonald ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Prefrontal Cortex ◽  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Trial Registration ◽  
Angular Gyrus ◽  
Open Label ◽  
Compulsive Disorder ◽  
Dorsomedial Prefrontal Cortex

Abstract Background Patients with anorexia nervosa (AN) face severe and chronic illness with high mortality rates, despite our best currently available conventional treatments. Repetitive transcranial magnetic stimulation (rTMS) has shown increasing efficacy in treatment-refractory cases across a variety of psychiatric disorders comorbid with AN, including major depression, Obsessive Compulsive Disorder (OCD), and Post traumatic Stress Disorder (PTSD). However, to date few studies have examined the effects of a course of rTMS on AN pathology itself. Methods Nineteen patients with AN underwent a 20–30 session open-label course of dorsomedial prefrontal rTMS for comorbid Major Depressive Disorder (MDD) ± PTSD. Resting-state functional MRI was acquired at baseline in 16/19 patients. Results Following treatment, significant improvements were seen in core AN pathology on the EDE global scale, and to a lesser extent on the shape and weight concerns subscales. Significant improvements in comorbid anxiety, and to a lesser extent depression, also ensued. The greatest improvements were seen in patients with lower baseline functional connectivity from the dorsomedial prefrontal cortex (DMPFC) target to regions in the right frontal pole and left angular gyrus. Conclusions Despite the limited size of this preliminary, open-label study, the results suggest that rTMS is safe in AN, and may be useful in addressing some core domains of AN pathology. Other targets may also be worth studying in this population, in future sham-controlled trials with larger sample sizes. Trial registration Trial registration ClinicalTrials.gov NCT04409704. Registered May 282,020. Retrospectively registered.

scholarly journals Developmental up-regulation of NMDA receptors in the prefrontal cortex and hippocampus of mGlu5 receptor knock-out mice

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tiziana Imbriglio ◽  
Remy Verhaeghe ◽  
Nico Antenucci ◽  
Stefania Maccari ◽  
Giuseppe Battaglia ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nmda Receptor ◽  
Metabotropic Glutamate Receptors ◽  
Adult Life ◽  
Developmental Time ◽  
Postnatal Life ◽  
Developmental Studies ◽  
Knock Out ◽  
Nmda Receptor Subunits ◽  
The Impact

AbstractmGlu5 metabotropic glutamate receptors are highly expressed and functional in the early postnatal life, and are known to positively modulate NMDA receptor function. Here, we examined the expression of NMDA receptor subunits and interneuron-related genes in the prefrontal cortex and hippocampus of mGlu5−/− mice and wild-type littermates at three developmental time points (PND9, − 21, and − 75). We were surprised to find that expression of all NMDA receptor subunits was greatly enhanced in mGlu5−/− mice at PND21. In contrast, at PND9, expression of the GluN2B subunit was enhanced, whereas expression of GluN2A and GluN2D subunits was reduced in both regions. These modifications were transient and disappeared in the adult life (PND75). Changes in the transcripts of interneuron-related genes (encoding parvalbumin, somatostatin, vasoactive intestinal peptide, reelin, and the two isoforms of glutamate decarboxylase) were also observed in mGlu5−/− mice across postnatal development. For example, the transcript encoding parvalbumin was up-regulated in the prefrontal cortex of mGlu5−/− mice at PND9 and PND21, whereas it was significantly reduced at PND75. These findings suggest that in mGlu5−/− mice a transient overexpression of NMDA receptor subunits may compensate for the lack of the NMDA receptor partner, mGlu5. Interestingly, in mGlu5−/− mice the behavioral response to the NMDA channel blocker, MK-801, was significantly increased at PND21, and largely reduced at PND75. The impact of adaptive changes in the expression of NMDA receptor subunits should be taken into account when mGlu5−/− mice are used for developmental studies.

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