scholarly journals Modeling age‐dependent developmental changes in the expression of genes involved in citrulline synthesis using pig enteroids

2020 ◽  
Vol 8 (21) ◽  
Author(s):  
Mahmoud A. Mohammad ◽  
Inka C. Didelija ◽  
Barbara Stoll ◽  
Douglas G. Burrin ◽  
Juan C. Marini
Keyword(s):  
Developmental Changes ◽  
Expression Of Genes ◽  
Age Dependent ◽  
Citrulline Synthesis

scholarly journals Age-dependent changes in electrophysiology and calcium handling – implications for pediatric cardiac research

2019 ◽  
Author(s):  
Luther M. Swift ◽  
Morgan Burke ◽  
Devon Guerrelli ◽  
Manelle Ramadan ◽  
Marissa Reilly ◽  
...  
Keyword(s):  
Postnatal Development ◽  
Cardiac Electrophysiology ◽  
Calcium Handling ◽  
Cell Coupling ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Age Dependent ◽  
Genes Encoding ◽  
Cardiac Maturation

ABSTRACTRationaleThe heart continues to develop and mature after birth and into adolescence. Accordingly, cardiac maturation is likely to include a progressive refinement in both organ morphology and function during the postnatal period. Yet, age-dependent changes in cardiac electrophysiology and calcium handling have not yet been fully characterized.ObjectiveThe objective of this study, was to examine the relationship between cardiac maturation, electrophysiology, and calcium handling throughout postnatal development in a rat model.MethodsPostnatal rat cardiac maturation was determined by measuring the expression of genes involved in cell-cell coupling, electrophysiology, and calcium handling. In vivo electrocardiograms were recorded from neonatal, juvenile, and adult animals. Simultaneous dual optical mapping of transmembrane voltage and calcium transients was performed on isolated, Langendorff-perfused rat hearts (postnatal day 0–3, 4-7, 8-14, adult).ResultsYounger, immature hearts displayed slowed electrical conduction, prolonged action potential duration and increased ventricular refractoriness. Slowed calcium handling in the immature heart increased the propensity for calcium transient alternans which corresponded to alterations in the expression of genes encoding calcium handling proteins. Developmental changes in cardiac electrophysiology were associated with the altered expression of genes encoding potassium channels and intercalated disc proteins.ConclusionUsing an intact whole heart model, this study highlights chronological changes in cardiac electrophysiology and calcium handling throughout postnatal development. Results of this study can serve as a comprehensive baseline for future studies focused on pediatric cardiac research, safety assessment and/or preclinical testing using rodent models.

Developmental changes in KCNQ2 and KCNQ3 expression in human brain: Possible contribution to the age-dependent etiology of benign familial neonatal convulsions

2008 ◽  
Vol 30 (5) ◽  
pp. 362-369 ◽  
Author(s):  
Takeshi Kanaumi ◽  
Sachio Takashima ◽  
Hiroshi Iwasaki ◽  
Masayuki Itoh ◽  
Akihisa Mitsudome ◽  
...  
Keyword(s):  
Human Brain ◽  
Developmental Changes ◽  
Age Dependent ◽  
Neonatal Convulsions

Response to caffeine and ryanodine receptor isoforms in mouse skeletal muscles

2001 ◽  
Vol 281 (2) ◽  
pp. C585-C594 ◽  
Author(s):  
R. Rossi ◽  
R. Bottinelli ◽  
V. Sorrentino ◽  
C. Reggiani
Keyword(s):  
Ryanodine Receptor ◽  
Skeletal Muscles ◽  
Calcium Release ◽  
Contractile Response ◽  
Developmental Changes ◽  
Wild Type ◽  
Adult Mice ◽  
Receptor Isoforms ◽  
Age Dependent ◽  
Permeabilized Muscle

The response to caffeine was studied in mouse muscles [diaphragm, soleus, and extensor digitorum longus (EDL)] with different ryanodine receptor isoform (RyR1, RyR3) composition and in single permeabilized muscle fibers dissected from diaphragm of wild-type (WT) and RyR3-deficient (RyR3−/−) mice at 1, 15, 30, and 60 postnatal days (PND). The caffeine response decreased during development, and, in adult mice, was greater in diaphragm, lower in EDL, and intermediate in soleus. This suggests a direct relation between response to caffeine and RyR3 expression. The lack of RyR3 reduced caffeine response in young, but not in adult mice, and did not abolish the age-dependent variation and the intermuscle differences. In diaphragm single fibers, the response to caffeine increased during development and was reduced in fibers lacking RyR3 both at 15 and 60 PND. A population of fibers highly responsive to caffeine was present in adult WT and disappeared in RyR3−/−. The results confirm the contribution of RyR3 to calcium release for contractile response and clarify the contribution of RyR3 to developmental changes and intermuscle differences.

scholarly journals Determining the Role of ApoE4 in Age-Related Cerebrovascular Decline

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 118-119
Author(s):  
Kate Foley ◽  
Peter Borchian ◽  
Dylan Garceau ◽  
Kevin Kotredes ◽  
Paul Territo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Transcriptional Profiling ◽  
Genetic Risk Factors ◽  
Expression Of Genes ◽  
Age Related ◽  
Age Dependent ◽  
Cerebrovascular Health ◽  
E4 Allele

Abstract Cerebrovascular decline occurs during aging and may be critical during prodromal phases of Alzheimer’s disease (AD). The E4 allele of apolipoprotein E (APOE4) is the greatest genetic risk factor for AD and decreased longevity and studies suggest APOE4 increases risk for age-dependent cerebrovascular damage. To study the relationship between APOE4 and age-related cerebrovascular decline, male and female C57BL/6J (B6) mice carrying combinations of APOE alleles including APOE4 (risk) and APOE3 (neutral), as well as B6 controls were assessed at a variety of ages from 4 to 24 mos for cognitive ability, biometrics and cerebrovascular health including i) PET/MRI using 64Cu-PTSM (perfusion) and 18F-FDG (metabolism), ii) transcriptional profiling and iii) immunofluorescence. Despite no cognitive decline, male APOE4 mice showed hypo-perfusion and hypo-metabolism by 12 mos, while female APOE4 mice showed an uncoupled hyper-perfusion and hypo-metabolism phenotype. Transcriptional profiling showed differential expression of genes involved in regulation of cerebral perfusion, glucose transportation and metabolism in APOE4 mice. An age-dependent blood brain barrier compromise was also apparent in the brains of female APOE4 mice. Physical activity reduces risk for human AD and our data shows exercise improves cerebrovascular health in mice. However, the effects to cerebrovascular health in individuals carrying genetic risk factors such as APOE4 are not known. To determine whether exercise can overcome APOE4-dependent cerebrovascular damage, APOE mice are being exercised from 2-4 and to 2-12 mos. Transcriptional profiling and immunofluorescence will determine whether the benefits of exercise to the cerebrovasculature are modulated by genetic risk factors such as APOE4.

scholarly journals Developmental Changes in the Spatial Expression of Genes Involved in Myosin Function in Dictyostelium

2000 ◽  
Vol 223 (1) ◽  
pp. 114-119 ◽  
Author(s):  
Mineko Maeda ◽  
Hidekazu Kuwayama ◽  
Masako Yokoyama ◽  
Keiko Nishio ◽  
Takahiro Morio ◽  
...  
Keyword(s):  
Developmental Changes ◽  
Spatial Expression ◽  
Expression Of Genes

scholarly journals Postnatal developmental changes in CO2 sensitivity in rats

2006 ◽  
Vol 101 (4) ◽  
pp. 1097-1103 ◽  
Author(s):  
S. E. Davis ◽  
G. Solhied ◽  
M. Castillo ◽  
M. Dwinell ◽  
D. Brozoski ◽  
...  
Keyword(s):  
Pulmonary Ventilation ◽  
Strain Differences ◽  
Developmental Changes ◽  
Brown Norway ◽  
Sprague Dawley ◽  
Dependent Plasticity ◽  
Co2 Sensitivity ◽  
Age Dependent ◽  
High Degree ◽  
Physiological Systems

Ventilatory sensitivity to CO2 in awake adult Brown Norway (BN) rats is 50–75% lower than in adult Sprague-Dawley (SD) and salt-sensitive Dahl S (SS) rats. The purpose of the present study was to test the hypothesis that this difference would be apparent during the development of CO2 sensitivity. Four litters of each strain were divided into four groups such that rats were exposed to 7% inspired CO2 for 5 min in a plethysmograph every third day from postnatal day (P) 0 to P21 and again on P29 and P30. From P0 to P14, CO2 exposure increased pulmonary ventilation (V̇e) by 25–50% in the BN and SD strains and between 25 to over 200% in the SS strain. In all strains beginning around P15, the response to CO2 increased progressively reaching a peak at P19–21 when V̇e during hypercapnia was 175–225% above eucapnia. There were minimal changes in CO2 sensitivity between P21 and P30, and at both ages there were minimal between-strain differences. At P30, the response to CO2 in the SS and SD strains was near the adult response, but the response in the BN rats was 100% greater at P30 than in adults. We conclude that 1) CO2-sensing mechanisms, and/or mechanisms downstream from the chemoreceptors, change dramatically at the age in rats when other physiological systems are also maturing (∼P15), and 2) there is a high degree of age-dependent plasticity in CO2 sensitivity in rats, which differs between strains.

Developmental changes in alpha 1-adrenergic receptors, IP3 responses, and NE-induced contraction in cerebral arteries

1996 ◽  
Vol 271 (6) ◽  
pp. H2313-H2319 ◽  
Author(s):  
L. D. Longo ◽  
N. Ueno ◽  
Y. Zhao ◽  
W. J. Pearce ◽  
L. Zhang
Keyword(s):  
Cerebral Artery ◽  
Adrenergic Receptors ◽  
Cerebral Arteries ◽  
Developmental Changes ◽  
Developmental Age ◽  
Age Dependent ◽  
Density Values ◽  
The Common ◽  
Pharmacomechanical Coupling ◽  
Dose Dependent

Cerebral arteries show significant developmental and artery-specific changes in noradrenergic-mediated contraction. To test the hypothesis that these changes result from differences in the density of alpha 1-adrenergic receptors (alpha 1-ARs) and/or norepinephrine (NE)-induced inositol 1,4,5-trisphosphate [Ins(1,4,5)P3,IP3] synthesis, we quantified these variables and the NE-induced contraction in the common carotid artery (Com) and main branch cerebral arteries (MBC) from term fetal (approximately 140 gestational day) and newborn (2- to 5-day) sheep and compared them with adult values. In fetal and newborn Com, maximal contractions to NE (percent K+ maximum response) were 132 +/- 14 and 118 +/- 9%, respectively (adult = 92 +/- 7%). For fetal and newborn middle cerebral artery, these values were 34 +/- 10 and 43 +/- 7%, respectively (adult = 24 +/- 7%). alpha 1-AR density values in Com of fetal and newborn sheep were 113 +/- 18 and 106 +/- 4 fmol/mg protein, respectively (adult = 54 +/- 3 fmol/mg protein). For the MBC, density values were 47 +/- 2 and 24 +/- 3 fmol/mg protein, respectively (adult = 23 +/- 3 fmol/protein). In term fetal and newborn MBC, NE produced dose-dependent increases in Ins(1,4,5)P3, the maximal increases above basal values being 245 +/- 40 and 189 +/- 16%, respectively (adult = 254 +/- 35%). Neither fetus nor newborn Com showed significant Ins(1,4,5)P3 responses to NE. We concluded that in fetal and newborn Com and MBC, alpha 1-AR density and NE-induced Ins(1,4,5)P3 response varied as a function of developmental age and specific vessel. However, these variations did not correlate with NE-induced maximum contraction. Thus we reject the hypothesis that age-dependent and vessel-specific differences of cerebral artery adrenergic-mediated contraction are a function of alpha 1-AR density or Ins(1,4,5)P3 response. Rather, the differences would appear to result from other factors such as non-Ins(1,4,5)P3-mediated calcium activation and/or sensitivity to Ins(1,4,5)P3. The studies also suggest considerable potential for maturational modulation of pharmacomechanical coupling and homeostatic regulation of cerebrovascular tone.

scholarly journals Effect of thyroid hormone on metabolic compartmentation in the developing rat brain

1971 ◽  
Vol 121 (3) ◽  
pp. 469-481 ◽  
Author(s):  
A. J. Patel ◽  
R. Balázs
Keyword(s):  
Amino Acids ◽  
Thyroid Hormone ◽  
Tricarboxylic Acid Cycle ◽  
Specific Radioactivity ◽  
Tricarboxylic Acid ◽  
The Other ◽  
Developmental Changes ◽  
Acid Cycle ◽  
Metabolic Compartmentation ◽  
Age Dependent

1. The effects of treatment with thyroid hormone (tri-iodothyronine) and of neonatal thyroidectomy on the cerebral metabolism of [U-14C]leucine were investigated during the period of functional maturation of the rat brain extending from 9 to 25 days after birth. 2. Age-dependent changes in the labelling of brain constituents under normal conditions appear to depend on changes in the availability of blood-borne [14C]leucine resulting from differential rates of growth of body and brain; but developmental changes in the pool size of free leucine and in the rates of protein synthesis and oxidation of leucine are also involved. 3. Treatment with thyroid hormone had no significant effect on the conversion of leucine carbon into proteins and lipids; and the age-dependent changes in the concentration and specific radioactivity of leucine were similar to controls. On the other hand there was an acceleration in the conversion of leucine carbon into amino acids associated with the tricarboxylic acid cycle. These observations indicate that leucine oxidation was the process mainly affected. 4. The specific radioactivity of glutamine relative to that of glutamate was used as an index of metabolic compartmentation in brain tissue. Treatment with thyroid hormone advanced the development of metabolic compartmentation. 5. Neonatal thyroidectomy led to a marked decrease in the conversion of leucine carbon into proteins and lipids and to a significant increase in the amount of 14C combined in the amino acids associated with the tricarboxylic acid cycle. The age-dependent increase in the glutamate/glutamine specific-radioactivity ratio was strongly retarded. 6. The increased conversion of leucine carbon into cerebral amino acids applied to glutamate and aspartate, but not to glutamine and γ-aminobutyrate. This observation facilitated the understanding of the effects of thyroid deprivation on brain metabolism and provided new evidence for the allocation of morphological structures to the metabolic compartments in brain tissue. 7. In contrast with the marked effects of the thyroid state on metabolic compartmentation, it had relatively little effect on the developmental changes in the concentration of amino acids in the brain. 8. The rate of conversion of leucine carbon into the ‘cycle amino acids’ both under normal conditions and in thyroid deficiency indicated a special metabolic relationship between glutamate and aspartate on the one hand, and glutamine and γ-aminobutyrate on the other.

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