A Novel Knockout Mouse Model of the Noncoding Antisense  Brain-Derived Neurotrophic Factor (Bdnf) Gene Displays Increased Endogenous Bdnf Protein and Improved Memory Function Following Exercise

2020 ◽  
Author(s):  
Farzaneh Modarresi ◽  
Roya Pedram-Fatemi ◽  
Seyedeh Fatemeh Razavipour ◽  
Natalie Ricciardi ◽  
Madina Makhmutova ◽  
...  
Keyword(s):  
Mouse Model ◽  
Neurotrophic Factor ◽  
Knockout Mouse ◽  
Memory Function ◽  
Brain Derived Neurotrophic Factor ◽  
Knockout Mouse Model ◽  
I Gene

Temporal dissection of Rai1 function reveals brain-derived neurotrophic factor as a potential therapeutic target for Smith-Magenis syndrome

2021 ◽  
Author(s):  
Sehrish Javed ◽  
Yu-Ju Lee ◽  
Jin Xu ◽  
Wei-Hsiang Huang
Keyword(s):  
Mouse Model ◽  
Neurotrophic Factor ◽  
Neurodevelopmental Disorder ◽  
Brain Derived Neurotrophic Factor ◽  
Knockout Mouse Model ◽  
Obesity In Mice ◽  
Bdnf Signaling ◽  
Neurobehavioral Deficits ◽  
Developmental Windows

Abstract Haploinsufficiency of RAI1 is responsible for Smith-Magenis Syndrome (SMS), a childhood neurodevelopmental disorder associated with hyperphagia, obesity, and autistic features. We previously showed that constitutive inactivation of one or both copies of Rai1 in the germline or developing brain induces SMS-like neurobehavioral deficits and obesity in mice. By contrast, the postnatal function of Rai1 is unclear. Here, we globally deleted one or both copies of Rai1 during two postnatal developmental windows by generating an inducible Rai1 knockout mouse model. We found that delayed Rai1 deletion at 3 or 8 weeks of age had no effect on neurobehavioral functions but resulted in adult-onset obesity and decreased expression of brain-derived neurotrophic factor (Bdnf) in the hypothalamus. Remarkably, genetic overexpression of human Bdnf in Rai1 heterozygous mice reversed SMS-like obesity, hyperphagia, metabolic syndrome-like features, and hyposociability. Increasing Bdnf signaling in the paraventricular nucleus of the hypothalamus (PVH) or the ventromedial nucleus of the hypothalamus (VMH) was sufficient to mediate the anti-obesity effect. Our work identifies the function of Rai1 in different temporal windows after birth and provides in vivo evidence that increasing Bdnf signaling is therapeutically effective in a preclinical mouse model of SMS.

scholarly journals DNase1 Does Not Appear to Play a Major Role in the Fragmentation of Plasma DNA in a Knockout Mouse Model

2018 ◽  
Vol 64 (2) ◽  
pp. 406-408 ◽  
Author(s):  
Timothy H T Cheng ◽  
Kathy O Lui ◽  
Xianlu Laura Peng ◽  
Suk Hang Cheng ◽  
Peiyong Jiang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Knockout Mouse ◽  
Plasma Dna ◽  
Knockout Mouse Model

scholarly journals The Function of Selenium in Central Nervous System: Lessons from MsrB1 Knockout Mouse Models

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1372
Author(s):  
Tengrui Shi ◽  
Jianxi Song ◽  
Guanying You ◽  
Yujie Yang ◽  
Qiong Liu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Synaptic Plasticity ◽  
Mouse Model ◽  
Mouse Models ◽  
Knockout Mouse ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Knockout Mouse Model ◽  
The Central Nervous System

MsrB1 used to be named selenoprotein R, for it was first identified as a selenocysteine containing protein by searching for the selenocysteine insert sequence (SECIS) in the human genome. Later, it was found that MsrB1 is homologous to PilB in Neisseria gonorrhoeae, which is a methionine sulfoxide reductase (Msr), specifically reducing L-methionine sulfoxide (L-Met-O) in proteins. In humans and mice, four members constitute the Msr family, which are MsrA, MsrB1, MsrB2, and MsrB3. MsrA can reduce free or protein-containing L-Met-O (S), whereas MsrBs can only function on the L-Met-O (R) epimer in proteins. Though there are isomerases existent that could transfer L-Met-O (S) to L-Met-O (R) and vice-versa, the loss of Msr individually results in different phenotypes in mice models. These observations indicate that the function of one Msr cannot be totally complemented by another. Among the mammalian Msrs, MsrB1 is the only selenocysteine-containing protein, and we recently found that loss of MsrB1 perturbs the synaptic plasticity in mice, along with the astrogliosis in their brains. In this review, we summarized the effects resulting from Msr deficiency and the bioactivity of selenium in the central nervous system, especially those that we learned from the MsrB1 knockout mouse model. We hope it will be helpful in better understanding how the trace element selenium participates in the reduction of L-Met-O and becomes involved in neurobiology.

scholarly journals Modulation of Brain-Derived Neurotrophic Factor (BDNF) Signaling Pathway by Culinary Sage (Salvia officinalis L.)

2021 ◽  
Vol 22 (14) ◽  
pp. 7382
Author(s):  
Nancy Chiang ◽  
Shahla Ray ◽  
Jade Lomax ◽  
Sydney Goertzen ◽  
Slavko Komarnytsky ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Neurotrophic Factor ◽  
High Performance ◽  
Memory Function ◽  
Brain Derived Neurotrophic Factor ◽  
Salvia Officinalis ◽  
C6 Glioma Cells ◽  
Medicinal Uses ◽  
Bdnf Signaling ◽  
Salvia Officinalis L

Culinary sage (Salvia officinalis L.) is a common spice plant in the mint family (Lamiaceae) well known for its distinctive culinary and traditional medicinal uses. Sage tea has been used traditionally as a brain-enhancing tonic and extracts from sage have been reported to have both cognitive and memory enhancing effects. Brain-derived neurotrophic factor (BDNF) is an endogenous signaling molecule involved in cognition and memory function. In this study, activity-guided fractionation employing preparative reverse-phase high performance liquid chromatography (RP-HPLC) of culinary sage extracts led to the discovery of benzyl 6-O-β-D-apiofuranosyl-β-D-glucoside (B6AG) as a natural product that upregulates transcription of neurotrophic factors in C6 glioma cells. Purified B6AG showed a moderate dose response, with upregulation of BDNF and with EC50 at 6.46 μM. To better understand the natural variation in culinary sage, B6AG was quantitated in the leaves of several commercial varieties by liquid chromatography-mass spectrometry (LC-MS). The level of B6AG in dried culinary sage was found to range from 334 ± 14 to 698 ± 65 μg/g. This study provided a foundation for future investigations, including quantitative inquiries on the distribution of B6AG within the different plant organs, explorations in optimizing post-harvest practices, and aid in the development of sage varieties with elevated levels of B6AG.

scholarly journals The First Knockout Mouse Model of Retinoblastoma

Cell Cycle ◽  
2004 ◽  
Vol 3 (7) ◽  
pp. 950-957 ◽  
Author(s):  
Jiakun Zhang ◽  
Brett Schweers ◽  
Michael A. Dyer
Keyword(s):  
Mouse Model ◽  
Knockout Mouse ◽  
Knockout Mouse Model
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