Abstract:
BACKGROUND:Lead (Pb2+) is an environmental neurotoxicant that disrupts neurodevelopment, communication, and organization through competition with Ca2+ signaling. How perinatal Pb2+ exposure affects Ca2+-related gene regulation remains unclear. However, Ca2+ activates the L-Type voltage sensitive calcium channel β-3 subunit (Ca-β3), which autoregulates neuronal excitability and plays a role in the GABA-shift from excitatory-to-inhibitory neurotransmission. METHOD:A total of eight females (n = 4 Control and n = 4 Perinatal) and four males (n = 2 Control and n = 2 Perinatal) rats were used as breeders to serve as Dams and Sires. The Dam's litters each ranged from N = 6-10 pups per litter (M = 8, SD = 2), irrespective of Pb2+ treatment, with a majority of males over females. Since there were more males in each of the litters than females, to best assess and equally control for Pb2+- and litter-effects across all developmental time-points under study, female pups were excluded due to an insufficient sample size availability from the litter's obtained. From the included pup litters, 24 experimentally naïve male Long Evans hooded rat pups (Control N = 12; Pb2+ N = 12) were used in the present study. Brains were extracted from rat prefrontal cortex (PFC) and hippocampus (HP) at postnatal day (PND) 2, 7, 14 and 22, were homogenized in 1 mL of TRIzol reagent per 100 mg of tissue using a glass-Teflon homogenizer. Post-centrifugation, RNA was extracted with chloroform and precipitated with isopropyl alcohol. RNA samples were then re-suspended in 100 μL of DEPC treated H2O. Next, 10 μg of total RNA was treated with RNase-free DNase (Qiagen) at 37 °C for 1 h and re-purified by a 3:1 phenol/chloroform extraction followed by an ethanol precipitation. From the purified RNA, 1 μg was used in the SYBR GreenER Two-Step qRT-PCR kit (Invitrogen) for first strand cDNA synthesis and the quantitative real-time PCR (qRT-PCR). The effects of perinatal Pb2+ exposure on genes related to early neuronal development and the GABA-shift were evaluated through the expression of: Ca-β3, GABAAR-β3, NKCC1, KCC2, and GAD 80, 86, 65, and 67 isoforms. RESULTS:Perinatal Pb2+ exposure significantly altered the GABA-shift neurodevelopmental GOI expression as a function of Pb2+ exposure and age across postnatal development. Dramatic changes were observed with Ca-β3 expression consistent with a Pb2+ competition with L-type calcium channels. By PND 22, Ca-β3 mRNA was reduced by 1-fold and 1.5-fold in PFC and HP respectively, relative to controls. All HP GABA-β3 mRNA levels were particularly vulnerable to Pb2+ at PND 2 and 7, and both PFC and HP were negatively impacted by Pb2+ at PND 22. Additionally, Pb2+ altered both the PFC and HP immature GAD 80/86 mRNA expression particularly at PND 2, whereas mature GAD 65/67 were most significantly affected by Pb2+ at PND 22. CONCLUSIONS:Perinatal Pb2+ exposure disrupts the expression of mRNAs related to the GABA-shift, potentially altering the establishment, organization, and excitability of neural circuits across development. These findings offer new insights into the altered effects Pb2+ has on the GABAergic system preceding what is known regarding Pb2+ insults unto the glutamatergic system.
journal_name
J Biomed Scijournal_title
Journal of biomedical scienceauthors
Neuwirth LS,Phillips GR,El Idrissi Adoi
10.1186/s12929-018-0450-4subject
Has Abstractpub_date
2018-05-24 00:00:00pages
45issue
1eissn
1021-7770issn
1423-0127pii
10.1186/s12929-018-0450-4journal_volume
25pub_type
杂志文章abstract::With the advances in deep sequencing-based transcriptome profiling technology, it is now known that human genome is transcribed more pervasively than previously thought. Up to 90% of the human DNA is transcribed, and a large proportion of the human genome is transcribed as long noncoding RNAs (lncRNAs), a heterogenous...
journal_title:Journal of biomedical science
pub_type: 杂志文章,评审
doi:10.1186/s12929-020-00647-w
更新日期:2020-04-02 00:00:00
abstract:BACKGROUND:NKG2D, an activating immunoreceptor, is primarily restricted to NK cells and CD8(+) T cells. The existence of an atypical cytotoxic CD4(+)NKG2D(+) T cell population has also been found in patients with autoimmune dysfunctions. Nonetheless, contradictory evidence has categorized this population with a regulat...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1186/s12929-015-0190-7
更新日期:2015-10-20 00:00:00
abstract:BACKGROUND:The diastolic oscillatory after-potential Vos and pre-potential ThVos play an essential role in the pacemaker mechanism of sino-atrial node (SAN). The aim of this study was to investigate whether these oscillatory potentials are also involved in adrenergic control of SAN discharge. METHODS:Vos and ThVos wer...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1186/1423-0127-16-101
更新日期:2009-11-18 00:00:00
abstract::The effects of N omega-nitro-L: -arginine (L: -NOARG) and N(G)-monomethyl-L: -arginine (L: -NMMA) on the spatial distribution of diaphragmatic microvascular blood flow were assessed in anesthetized, mechanically ventilated rats. Microvascular blood flow was measured after different periods at either a fixed site (Q st...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1007/s11373-004-8166-8
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Poly(ADP-ribose) is a NAD+-requiring, DNA-repairing, enzyme playing a central role in pancreatic beta-cell death and in the development of endothelial dysfunction in humans and experimental animals. PARP activation is also relevant to the development of complications of diabetes. Hence, agents capable of inh...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1186/1423-0127-17-S1-S16
更新日期:2010-08-24 00:00:00
abstract::Stem cell activity is subject to non-cell-autonomous regulation from the local microenvironment, or niche. In adaption to varying physiological conditions and the ever-changing external environment, the stem cell niche has evolved with multifunctionality that enables stem cells to detect these changes and to communica...
journal_title:Journal of biomedical science
pub_type: 杂志文章,评审
doi:10.1186/s12929-020-0624-8
更新日期:2020-03-14 00:00:00
abstract::Advances in Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated system (CRISPR/Cas9) has dramatically reshaped our ability to edit genomes. The scientific community is using CRISPR/Cas9 for various biotechnological and medical purposes. One of its most important uses is developing potential the...
journal_title:Journal of biomedical science
pub_type: 杂志文章,评审
doi:10.1186/s12929-018-0425-5
更新日期:2018-03-28 00:00:00
abstract::Glucocorticoids regulate the expression of many liver-specific genes via glucocorticoid receptors. The presence of glucocorticoid receptors in liver has been reported in many mammalian species but not in nude mice. In the present study, we demonstrate the presence of specific glucocorticoid receptors in nude mouse liv...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1007/BF02253306
更新日期:1994-10-01 00:00:00
abstract::In all eukaryotes, the plasma membrane is critically important as it maintains the architectural integrity of the cell. Proper anchorage and interaction between the plasma membrane and the cytoskeleton is critical for normal cellular processes. The ERM (ezrin-radixin-moesin) proteins are a class of highly homologous p...
journal_title:Journal of biomedical science
pub_type: 杂志文章,评审
doi:10.1186/s12929-016-0246-3
更新日期:2016-03-17 00:00:00
abstract:BACKGROUND:Promoting post-stroke neurogenesis has long been proposed to be a therapeutic strategy for the enhancement of functional recovery after cerebral ischemic stroke. Despite numerous approaches have been widely reported the proliferation or differentiation of the neurogenic population therapeutic strategies by t...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1186/s12929-019-0521-1
更新日期:2019-04-18 00:00:00
abstract::After streptococcal pyrogenic exotoxin B (SPE B) induces apoptosis, its fate is unknown. Using confocal time-course microscopy at 37 degrees C, we detected green fluorescence 20 min after adding FITC-SPE B. Orange fluorescence, an indication of co-localization of SPE B with lysosomes which were labeled with a red fluo...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1007/s11373-007-9154-6
更新日期:2007-05-01 00:00:00
abstract::The matrin 3 family of nuclear proteins consists of members with potentially diverse activities. Matrin 3 and NP220 share RNA-binding domains, and NP220 has been shown to recognize and bind to the DNA sequence, CCCCC (G/C). We have isolated and characterized another member of the matrin 3 family, designated NP94, from...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1007/BF02256432
更新日期:2003-07-01 00:00:00
abstract::Although hypercholesterolemia is a well-known risk factor for atherosclerosis, little is known about the effect of hypercholesterolemia on cardiac contractile function. The objective of this study was to examine the effect of hypercholesterolemia on myocardial contractility. Fifteen New Zealand white rabbits were fed ...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1007/BF02254368
更新日期:2004-11-01 00:00:00
abstract:BACKGROUND:Oxidized LDL (oxLDL) is involved in the development of atherosclerotic heart disease through a mechanism that is not fully understood. In this study, we examined the role of malondialdehyde (MDA), an important oxidative stress epitope of oxLDL, in mediating coronary endothelial cytotoxicity. RESULTS:Human c...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1186/1423-0127-21-11
更新日期:2014-02-03 00:00:00
abstract::Zebrafish tbx5 expresses in the heart, pectoral fins and eyes of zebrafish during embryonic development. In zebrafish, injection of tbx5 morpholino antisense RNA caused changes of heart conformation, defect of heart looping, pericardium effusion, dropsy of ventral position and decreased heart rate. We suggested that c...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1007/s11373-008-9268-5
更新日期:2008-11-01 00:00:00
abstract::Ischemia and reperfusion (I/R) - induced injury has been described as one of the main factors that contribute to the observed morbidity and mortality in a variety of clinical entities, including myocardial infarction, ischemic stroke, cardiac arrest and trauma. An imbalance between oxygen demand and supply, within the...
journal_title:Journal of biomedical science
pub_type: 杂志文章,评审
doi:10.1186/s12929-016-0220-0
更新日期:2016-01-19 00:00:00
abstract::A three-dimensional molecular model of the transmembrane domain of the 5-HT(1A) receptor (5-HT(1A)R) is presented in the context of a general strategy for modeling the macromolecular structure of a guanine nucleotide binding, regulatory protein coupled receptor (GPCR). The model of the 5-HT(1A)R rests on the definitio...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1007/BF02255537
更新日期:1996-04-01 00:00:00
abstract::The intracellular mechanisms underlying oxidized low-density lipoprotein (oxLDL)-signaling pathways in platelets are not yet completely understood. Therefore, the aim of this study was to further examine the effects of oxLDL in prevention of platelet aggregation. In this study, oxLDL concentration-dependently (40-120 ...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1007/s11373-005-9042-x
更新日期:2006-05-01 00:00:00
abstract::We previously reported that transgenic ablation of gonadotrophs results in impaired development of cells immunostainable for prolactin (PRL) but not of cells immunostainable for growth hormone (GH) or pro-opiomelanocortin (POMC) in pituitary of newborn mice. The question remained whether this reduction in PRL protein ...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1159/000073968
更新日期:2003-11-01 00:00:00
abstract::Metabolic diseases such as obesity, type 2 diabetes (T2D) and insulin resistance have attracted great attention from biomedical researchers and clinicians because of the astonishing increase in its prevalence. Decrease in the capacity of oxidative metabolism and mitochondrial dysfunction are a major contributor to the...
journal_title:Journal of biomedical science
pub_type: 杂志文章,评审
doi:10.1186/s12929-017-0375-3
更新日期:2017-09-07 00:00:00
abstract:BACKGROUND:B cells play an essential role during dengue viral infection. While a major expansion of antibody secreting cells (ASCs) was observed, the importance of these increased frequencies of ASCs remains unclear. The alteration of B cell subsets may result from the expression of tissue specific homing molecules lea...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1186/s12929-018-0467-8
更新日期:2018-08-27 00:00:00
abstract::Adeno-associated virus (AAV)-2 was developed as a useful vector for human gene therapy. In this report, we analyzed the integration and expression of AAV-mediated ex vivo transferred human beta-globin gene in bone marrow (BM) reconstituted mice. Recombinant AAV (rAAV) containing human beta-globin gene was packaged by ...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1007/BF02256072
更新日期:2002-05-01 00:00:00
abstract::Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy in terms of clinical features, underlying pathogenesis and treatment outcomes. Recent advances in genomic techniques have unraveled the molecular complexity of AML leukemogenesis, which in turn have led to refinement of risk stratification and pers...
journal_title:Journal of biomedical science
pub_type: 杂志文章,评审
doi:10.1186/s12929-020-00674-7
更新日期:2020-07-21 00:00:00
abstract:BACKGROUND:Pulmonary emphysema is characterized histologically by destruction of alveolar walls and enlargement of air spaces due to lung epithelial cell apoptosis. Cell adhesion molecule 1 (CADM1) is an immunoglobulin superfamily member expressed in lung epithelial cells. CADM1 generates a membrane-associated C-termin...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1186/s12929-015-0173-8
更新日期:2015-08-11 00:00:00
abstract::The ACTGCTGA sequence (CTG motif) is located immediately upstream of the NF-kappaB enhancer in the human immunodeficiency virus type-1 (HIV-1) long terminal repeat (LTR). We previously reported on the frequent duplication of this motif in HIV-1-infected individuals. In this study we further characterized the role of t...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1007/BF02257981
更新日期:1994-03-01 00:00:00
abstract:BACKGROUND:Angiotensin II (Ang II) signaling occurs via two major receptors which activate non-receptor tyrosin kinases that then interact with protein tyrosin-phosphatases (PTPs) to regulate cell function. SHP-2 is one such important PTP that also functions as an adaptor to promote downstream signaling pathway. Its ro...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1186/1423-0127-18-38
更新日期:2011-06-13 00:00:00
abstract::The interactive role of rostral ventrolateral medulla (RVL) cardiovascular neurons and brain angiotensin II (Ang II) in regulating the arterial blood pressure was examined by recording simultaneously the spontaneous activity of these spinal projecting neurons and the arterial blood pressure in the pentobarbital-anesth...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1007/BF02253100
更新日期:1996-05-01 00:00:00
abstract::Angiogenesis is essential for development, growth and advancement of solid tumors. Cyclooxygenase (COX)-2 is recognized as an angiogenic factor in various tumors. This prompted us to study the clinical implications of COX-2 expression related to angiogenesis in uterine cervical cancers. There was a significant correla...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1007/s11373-006-9114-6
更新日期:2006-11-01 00:00:00
abstract::Dehydroepiandrosterone (DHEA) is a putative anti-stress agent and stress is associated with the secretion of catecholamine from the adrenal gland, but the effects of DHEA on catecholamine secretion are not fully understood. Using bovine chromaffin cells, we found that DHEA inhibited catecholamine secretion and cytosol...
journal_title:Journal of biomedical science
pub_type: 杂志文章
doi:10.1007/BF02256563
更新日期:2004-03-01 00:00:00
abstract::Mitochondria are sub-cellular organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As suggested over 70 years ago by Otto Warburg and recently confirmed with molecular techniques, alterations in respiratory activity and in mitochondrial DNA (mtDNA) appear to be common featur...
journal_title:Journal of biomedical science
pub_type: 杂志文章,评审
doi:10.1186/1423-0127-17-31
更新日期:2010-04-25 00:00:00