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 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 The impact of quetiapine on the brain lipidome in a cuprizone-induced mouse model of schizophrenia

2020 ◽  
Vol 131 ◽  
pp. 110707
Author(s):  
Cui-hong Zhou ◽  
Shan-shan Xue ◽  
Fen Xue ◽  
Ling Liu ◽  
Jun-chang Liu ◽  
...  
Keyword(s):  
Mouse Model ◽  
The Impact ◽  
The Brain

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

Longitudinal Characterization of the Brain Proteomes for the Tg2576 Amyloid Mouse Model Using Shotgun Based Mass Spectrometry

2012 ◽  
Vol 11 (12) ◽  
pp. 6159-6174 ◽  
Author(s):  
Ganna Shevchenko ◽  
Magnus Wetterhall ◽  
Jonas Bergquist ◽  
Kina Höglund ◽  
Lars I. Andersson ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Mouse Model ◽  
The Brain

NCOG-41. HISTOLOGICAL ANALYSIS OF SLEEP AND CIRCADIAN BRAIN CIRCUITRY IN CRANIAL RADIATION-INDUCED HYPERSOMNOLENCE (C-RIH) MOUSE MODEL

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi161-vi161
Author(s):  
Dorela Shuboni-Mulligan ◽  
Demarrius Young Jr. ◽  
Julianie De La Cruz Minyety ◽  
Nicole Briceno ◽  
Amanda King ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mouse Model ◽  
Radiation Effects ◽  
Long Term Effects ◽  
Brain Volumes ◽  
Cranial Radiation ◽  
Radiation Induced ◽  
The Impact ◽  
The Brain

Abstract BACKGROUND Disrupted sleep, including daytime hypersomnolence, is a core symptom reported by primary brain tumor patients and often manifests after radiotherapy. The biological mechanisms driving cranial radiation-induced hypersomnolence (C-RIH) remain unclear but we hypothesize this may result from damage to neural circuits controlling sleep behavior. We developed a mouse model of C-RIH to explore the impact of radiation on the brain: examining region-specific differences in acute DNA damage response and neuroanatomic structure. METHODS Mice received whole brain radiation then behaviors were monitored using PhenoTyper® cages to determine optimal dose and long-term effects. To test short-term neurologic effects, brains were collected 1hr post-radiation then stained for γH2AX, a signal for DNA damage. Long-term effects were quantified 1-month post-treatment using neuroimaging to determine brain volume and T1 mapping changes in regions associated with sleep, circadian rhythms, and cognition. RESULTS Mice displayed decreased general activity and increased daytime sleep in a dose-dependent and sustained manner. Histologic staining demonstrated that DNA damage following radiation varies across the brain, with homeostatic sleep regions and cognitive regions expressing higher levels of γH2AX than the circadian suprachiasmatic nucleus. These findings were supported by in vitro studies comparing radiation effects in SCN and cortical astrocytes using both trypan blue (F(1,18)=235.937, p< 0.001) and clonogenic assays (F(1,24)=40.796, < 0.001). Brain volumes were significantly smaller in irradiated than sham animals in the hippocampus (t(4)=3.833, p=0.019) and the pontine central grey (t(4)=3.504, p=0.025). T1 maps also showed significant changes in relaxation times in many cognitive regions but not sleep or circadian areas. CONCLUSIONS These findings suggest that the homeostatic sleep region and cognitive circuits are vulnerable to radiation and may be relevant to the development of treatment plans in patients. We plan to introduce intracranial tumor to the model to evaluate the impact of timing of treatment and C-RIH on survival.

Intranasal delivery of phenytoin-loaded nanoparticles to the brain suppresses pentylenetetrazol-induced generalized tonic clonic seizures in epilepsy mouse model

2021 ◽  
Author(s):  
Amal Yousfan ◽  
Noelia Rubio Carrero ◽  
Mohamad Al-Ali ◽  
Abdul Hakim Nattouf ◽  
Houmam Kafa
Keyword(s):  
Mouse Model ◽  
Mouse Brain ◽  
Chitosan Nanoparticles ◽  
Intranasal Delivery ◽  
Anti Epileptic Drug ◽  
Clonic Seizures ◽  
The Brain

In this work we describe the preparation and characterization of lecithin-chitosan nanoparticles (L10Ci+), and investigate their ability to deliver the anti-epileptic drug phenytoin (PHT) to mouse brain following intranasal (IN)...

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