scholarly journals Sodium Leak Channel in the Nucleus Accumbens Modulates Ethanol-Induced Acute Stimulant Responses and Locomotor Sensitization in Mice: A Brief Research Report

2021 ◽  
Vol 15 ◽  
Author(s):  
Yujie Wu ◽  
Donghang Zhang ◽  
Jin Liu ◽  
Yaoxin Yang ◽  
Mengchan Ou ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nucleus Accumbens ◽  
Research Report ◽  
Locomotor Sensitization ◽  
Human Beings ◽  
Expression Levels ◽  
Leak Channel ◽  
Acute Responses ◽  
Increased Sensitivity ◽  
Excitability Of Neurons

Ethanol can induce acute stimulant responses in animals and human beings. Moreover, repeated exposure to ethanol may produce increased sensitivity to its acute locomotor stimulant actions, a process referred to as locomotor sensitization. The molecular mechanism of the development of acute stimulant responses and locomotor sensitization by ethanol is not fully understood. Sodium leak channel (NALCN) is widely expressed in central nervous system and controls the basal excitability of neurons. The present study aims to determine whether NALCN is implicated in the ethanol-induced acute responses and locomotor sensitization in mice. Here, our results showed that ethanol caused acute stimulant responses in DBA/2 mice. Locomotor sensitization was successfully induced following the sensitization procedure. Accordingly, the expression levels of NALCN mRNA and protein in the nucleus accumbens (NAc) were markedly increased in the sensitization mice compared to the control mice. Knockdown the expression levels of NALCN in the NAc alleviated both the ethanol-induced acute responses and locomotor sensitization. Our findings indicate that upregulation of NALCN expression in the NAc contributes to the ethanol-induced acute stimulant responses and locomotor sensitization in DBA/2 mice.

The Yin and Yang of BK Channels in Epilepsy

2018 ◽  
Vol 17 (4) ◽  
pp. 272-279 ◽  
Author(s):  
Yudan Zhu ◽  
Shuzhang Zhang ◽  
Yijun Feng ◽  
Qian Xiao ◽  
Jiwei Cheng ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Bk Channels ◽  
Bk Channel ◽  
Potential Shape ◽  
Yin And Yang ◽  
The Central Nervous System ◽  
Action Potential Shape ◽  
Excitability Of Neurons

Background & Objective: The large conductance calcium-activated potassium (BK) channel, extensively distributed in the central nervous system (CNS), is considered as a vital player in the pathogenesis of epilepsy, with evidence implicating derangement of K+ as well as regulating action potential shape and duration. However, unlike other channels implicated in epilepsy whose function in neurons could clearly be labeled “excitatory” or “inhibitory”, the unique physiological behavior of the BK channel allows it to both augment and decrease the excitability of neurons. Thus, the role of BK in epilepsy is controversial so far, and a growing area of intense investigation. Conclusion: Here, this review aims to highlight recent discoveries on the dichotomous role of BK channels in epilepsy, focusing on relevant BK-dependent pro- as well as antiepileptic pathways, and discuss the potential of BK specific modulators for the treatment of epilepsy.

scholarly journals Directed Evolution of AraC for Improved Compatibility of Arabinose- and Lactose-Inducible Promoters

2007 ◽  
Vol 73 (18) ◽  
pp. 5711-5715 ◽  
Author(s):  
Sung Kuk Lee ◽  
Howard H. Chou ◽  
Brian F. Pfleger ◽  
Jack D. Newman ◽  
Yasuo Yoshikuni ◽  
...  
Keyword(s):  
Directed Evolution ◽  
Cross Talk ◽  
Biological Systems ◽  
Wild Type ◽  
Dimerization Domain ◽  
Expression Levels ◽  
Inducible Promoters ◽  
C Terminus ◽  
Increased Sensitivity ◽  
Better Than

ABSTRACT Synthetic biological systems often require multiple, independently inducible promoters in order to control the expression levels of several genes; however, cross talk between the promoters limits this ability. Here, we demonstrate the directed evolution of AraC to construct an arabinose-inducible (PBAD) system that is more compatible with IPTG (isopropyl-β-d-1-thiogalactopyranoside) induction of a lactose-inducible (Plac) system. The constructed system is 10 times more sensitive to arabinose and tolerates IPTG significantly better than the wild type. Detailed studies indicate that the AraC dimerization domain and C terminus are important for the increased sensitivity of AraC to arabinose.

scholarly journals Polo-Like Kinase 4 (PLK4) Is Overexpressed in Central Nervous System Neuroblastoma (CNS-NB)

2018 ◽  
Vol 5 (4) ◽  
pp. 96 ◽  
Author(s):  
Anders Bailey ◽  
Amreena Suri ◽  
Pauline Chou ◽  
Tatiana Pundy ◽  
Samantha Gadd ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Tumors ◽  
Meta Analysis ◽  
P Value ◽  
Embryonal Tumors ◽  
Expression Levels ◽  
Embryonal Brain

Neuroblastoma (NB) is the most common extracranial solid tumor in pediatrics, with rare occurrences of primary and metastatic tumors in the central nervous system (CNS). We previously reported the overexpression of the polo-like kinase 4 (PLK4) in embryonal brain tumors. PLK4 has also been found to be overexpressed in a variety of peripheral adult tumors and recently in peripheral NB. Here, we investigated PLK4 expression in NBs of the CNS (CNS-NB) and validated our findings by performing a multi-platform transcriptomic meta-analysis using publicly available data. We evaluated the PLK4 expression by quantitative real-time PCR (qRT-PCR) on the CNS-NB samples and compared the relative expression levels among other embryonal and non-embryonal brain tumors. The relative PLK4 expression levels of the NB samples were found to be significantly higher than the non-embryonal brain tumors (p-value < 0.0001 in both our samples and in public databases). Here, we expand upon our previous work that detected PLK4 overexpression in pediatric embryonal tumors to include CNS-NB. As we previously reported, inhibiting PLK4 in embryonal tumors led to decreased tumor cell proliferation, survival, invasion and migration in vitro and tumor growth in vivo, and therefore PLK4 may be a potential new therapeutic approach to CNS-NB.

scholarly journals Impact of Oatp1c1 Deficiency on Thyroid Hormone Metabolism and Action in the Mouse Brain

Endocrinology ◽  
2012 ◽  
Vol 153 (3) ◽  
pp. 1528-1537 ◽  
Author(s):  
Steffen Mayerl ◽  
Theo J. Visser ◽  
Veerle M. Darras ◽  
Sigrun Horn ◽  
Heike Heuer
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Thyroid Hormone ◽  
Organic Anion ◽  
Mrna Levels ◽  
Expression Levels ◽  
Thyroid Hormone Metabolism ◽  
Serum T3 ◽  
Capillary Endothelial Cells ◽  
The Brain

Organic anion-transporting polypeptide 1c1 (Oatp1c1) (also known as Slco1c1 and Oatp14) belongs to the family of Oatp and has been shown to facilitate the transport of T4. In the rodent brain, Oatp1c1 is highly enriched in capillary endothelial cells and choroid plexus structures where it may mediate the entry of T4 into the central nervous system. Here, we describe the generation and first analysis of Oatp1c1-deficient mice. Oatp1c1 knockout (KO) mice were born with the expected frequency, were not growth retarded, and developed without any overt neurological abnormalities. Serum T3 and T4 concentrations as well as renal and hepatic deiodinase type 1 expression levels were indistinguishable between Oatp1c1 KO mice and control animals. Hypothalamic TRH and pituitary TSH mRNA levels were not affected, but brain T4 and T3 content was decreased in Oatp1c1-deficient animals. Moreover, increased type 2 and decreased type 3 deiodinase activities indicate a mild hypothyroid situation in the brain of Oatp1c1 KO mice. Consequently, mRNA expression levels of gene products positively regulated by T3 in the brain were down-regulated. This central nervous system-specific hypothyroidism is presumably caused by an impaired passage of T4 across the blood-brain barrier and indicates a unique function of Oatp1c1 in facilitating T4 transport despite the presence of other thyroid hormone transporters such as Mct8.

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