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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 757 records · Page 42
All sourcesNASA NTRSDOE OSTI
NASA NTRS1992

Parathyroid hormone induces c-fos and c-jun messenger RNA in rat osteoblastic cells

PTH is a potent regulator of osteoblast gene expression, yet the nuclear events that mediate PTH action are poorly understood. We were interested in identifying immediate early genes which may regulate PTH-altered gene expression in the osteoblast. Therefore, we examined the effects of PTH on c-fos and c-jun gene expression in a rat osteoblastic cell line (UMR 106-01). Under control conditions, c-fos and c-jun mRNAs were present at low basal levels. After PTH treatment, c-fos mRNA abundance dramatically increased, with a maximal and transient response at 30 min. PTH also stimulated an increase in c-jun mRNA, but in a biphasic manner, with maximal levels at 30 min and 2 h. These responses were dose dependent, not altered by cotreatment with the protein synthesis inhibitor cycloheximide, and preceded PTH-induced expression of matrix metallo-proteinase-1 mRNA. Nuclear run-on assays demonstrated an increased rate of c-fos and c-jun transcription after PTH exposure. To determine the signal transduction pathways involved, second messenger analogs were tested for their ability to mimic the effects of PTH. 8-Bromo-cAMP and phorbol 12-myristate 13-acetate (PMA) caused increases in the abundance of c-fos and c-jun transcripts. Ionomycin had no effect on the expression of these genes. Pretreatment of the cells with PMA resulted in a decrease in basal c-jun expression, but did not alter the PTH-mediated increase in c-fos, c-jun, or matrix metalloproteinase-1 mRNAs.(ABSTRACT TRUNCATED AT 250 WORDS).

Non-NASA Center↗
NASA NTRS1992

Regulation of an H-ras-related transcript by parathyroid hormone in rat osteosarcoma cells

The rat osteosarcoma cell line UMR 106-01 is a commonly used model system for the study of osteoblast function. However, it also expresses a phenotype characteristic of transformed cells. To test whether the latter could be accounted for by aberrant oncogene expression, we probed Northern blots of UMR and other osteoblastic cells with a panel of oncogene probes. These blots, when probed with a cDNA specific for v-H-ras, revealed a 7.0-kilobase (kb) H-ras-related transcript (designated HRRT) in UMR 106-01 cells that was not expressed in other osteoblastic cells. Osteoblast-enriched calvarial cells expressed the typical 1.1-kb H-ras mRNA, which was absent in UMR cells. Additionally, Western blots of lysates of UMR cells documented the presence of three proteins immunologically related to H-rasp21. To determine whether HRRT represented a recombinant retrovirus product, Northern blots were probed with a cDNA specific for the highly conserved gag-pol region of Moloney murine leukemia virus. These blots showed parallel cross-reactivity with an apparently identical transcript of 7.0 kb. The 7.0-kb transcripts detected by both v-H-ras and gag-pol probes declined to the same extent after treatment with concentrations of PTH known to inhibit proliferation of these cells. PTH regulated the abundance of HRRT in a time- and dose-dependent manner, with greatest repression of the transcript after 8 h of treatment with 10(-8) M PTH. The decrease in HRRT could not be completely accounted for by changes in transcriptional activity, as determined by nuclear run-on assays.(ABSTRACT TRUNCATED AT 250 WORDS).

Non-NASA Center↗
NASA NTRS1992

A dopaminergic projection to the rat mammillary nuclei demonstrated by retrograde transport of wheat germ agglutinin-horseradish peroxidase and tyrosine hydroxylase immunohistochemistry

The presence and distribution of dopaminergic neurons and terminals in the hypothalamus of the rat were studied by tyrosine hydroxylase (TH) immunohistochemistry. Strongly labelled TH-immunoreactive neurons were seen in the dorsomedial hypothalamic nucleus, periventricular region, zona incerta, arcuate nucleus, and supramammillary nucleus. A few TH-positive neurons were also identified in the dorsal and ventral premammillary nucleus, as well as the lateral hypothalamic area. TH-immunoreactive fibres and terminals were unevenly distributed in the mammillary nuclei; small, weakly labelled terminals were scattered in the medial mammillary nucleus, while large, strongly labelled, varicose terminals were densely concentrated in the internal part of the lateral mammillary nucleus. A few dorsoventrally oriented TH-positive axon bundles were also identified in the lateral mammillary nucleus. A dopaminergic projection to the mammillary nuclei from the supramammillary nucleus and lateral hypothalamic area was identified by double labelling with retrograde transport of wheat germ agglutinin-horseradish peroxidase and TH-immunohistochemistry. The lateral mammillary nucleus receives a weak dopaminergic projection from the medial, and stronger projections from the lateral, caudal supramammillary nucleus. The double-labelled neurons in the lateral supramammillary nucleus appear to encapsulate the caudal end of the mammillary nuclei. The medial mammillary nucleus receives a very light dopaminergic projection from the caudal lateral hypothalamic area. These results suggest that the supramammillary nucleus is the principal source of the dopaminergic input to the mammillary nuclei, establishing a local TH-pathway in the mammillary complex. The supramammillary cell groups are able to modulate the limbic system through its dopaminergic input to the mammillary nuclei as well as through its extensive dopaminergic projection to the lateral septal nucleus.

Non-NASA Center↗
NASA NTRS1992

Afferent projections to the mammillary complex of the rat, with special reference to those from surrounding hypothalamic regions

To better understand the functional organization of the mammillary nuclei, we investigated the afferents to this nuclear complex in the rat with iontophoretically injected wheat germ agglutinin conjugated to horseradish peroxidase. Particular attention was paid to tracing local hypothalamic afferents to these nuclei. Injections into the medial mammillary nucleus (MMN) revealed strong projections from the subicular region, and weaker projections from the prefrontal cortex, medial septum, and the nucleus of the diagonal band of Broca. Other descending subcortical projections to the MMN arise from the anterior and the lateral hypothalamic area, the medial preoptic area, and the bed nucleus of the stria terminalis. Ascending afferents to the MMN were found to originate in the raphe and various tegmental nuclei. Following all injections into the MMN, labelled neurons were found in nuclei surrounding the mammillary body. The lateral and posterior subdivisions of the tuberomammillary nucleus projected mainly to the pars medianus and pars medialis of the MMN. The dorsal and ventral premammillary nuclei projected to the pars lateralis of the MMN. The supramammillary nucleus at rostral level had a small projection to the pars medialis and lateralis of the MMN. However, the most obvious projection from this nucleus was to the pars posterior of the MMN, chiefly from the lateral part of the caudal supramammillary nucleus. Injections into the lateral mammillary nucleus revealed inputs from the presubiculum, parasubiculum, septal region, dorsal tegmental nucleus, dorsal raphe nucleus, and periaqueductal gray. In addition, the lateral mammillary nucleus was found to receive a moderate projection from the medial part of the supramammillary nucleus and stronger projections from the lateral part of the caudal supramammillary nucleus. A very light projection was also seen from the lateral and posterior subdivisions of the tuberomammillary nucleus. These findings add to our knowledge of the extensive and complex connectivity of the mammillary nuclei. In particular, the local connections we have demonstrated with the supramammillary and tuberomammillary nuclei indicate the existence of significant local circuits as well as circuits involving more distant brain regions such as the septal nuclei, subiculum, prefrontal cortex, and brain stem tegmentum.

Non-NASA Center↗
NASA NTRS1987

Hypogravity-induced atrophy of rat soleus and extensor digitorum longus muscles

Prolonged exposure of humans to hypogravity causes weakening of their skeletal muscles. This problem was studied in rats exposed to hypogravity for 7 days aboard Spacelab 3. Hindlimb muscles were harvested 12-16 hours postflight for histochemical, biochemical, and ultrastructural analyses. The majority of the soleus and extensor digitorum longus fibers exhibited simple cell shrinkage. However, approximately 1% of the fibers in flight soleus muscles appeared necrotic. Flight muscle fibers showed increased glycogen, lower subsarcolemmal staining for mitochondrial enzymes, and fewer subsarcolemmal mitochondria. During atrophy, myofibrils were eroded by multiple focal losses of myofilaments; lysosomal autophagy was not evident. Tripeptidylaminopeptidase and calcium-activated protease activities of flight soleus fibers were significantly increased, implying a role in myofibril breakdown. Simple fiber atrophy appears to account for muscle weakening during spaceflight, but fiber necrosis is also a contributing factor.

manned↗
NASA NTRS1988

Morphological evidence for parallel processing of information in rat macula

Study of montages, tracings and reconstructions prepared from a series of 570 consecutive ultrathin sections shows that rat maculas are morphologically organized for parallel processing of linear acceleratory information. Type II cells of one terminal field distribute information to neighboring terminals as well. The findings are examined in light of physiological data which indicate that macular receptor fields have a preferred directional vector, and are interpreted by analogy to a computer technology known as an information network.

Saccule and Utricle/ultrastructure↗
NASA NTRS2018

A Review and Comparison of Mouse and Rat Responses to Micro Gravity, Hyper Gravity and Simulated Models of Partial Gravity; Species Differences, Gaps in the Available Data, and Consideration of the Advantages and Caveats of Each Model for Spaceflight

Laboratory strains of mice and rat are widely used to study mammalian responses to stimulus, and both have been studied under a variety of gravity conditions, including space flight. We compared results obtained from exposure to spaceflight and microgravity, hyper gravity via centrifugation, earth gravity, and models of simulated partial gravity (hind-limb unloading and partial weight bearing treatments). We examined the reported changes in survival, body mass, circadian rhythm (body temperature and activity levels), behavior, bone, muscle, immune, cardio-vasculature, vestibular, reproduction and neonate survival, microbiome, and the visual system. Not all categories have published data for both species, some have limited data, and there are variations in experiment design that allow for only relative comparisons to be considered. The data reveal species differences in both the level of gravity required to obtain a response, degree of response, and in temporal expression of responses. Examination of the data across the gravity levels allows consideration of the hypothesis that gravitational responses follow a continuum, and organ specific differences are noted. In summary, we present advantages and caveats of each model system as pertains to gravitational biology research and identify gaps in our knowledge of how these mammals respond to gravity.

mouse rat gravity↗
DOE OSTI2020

Osteoporosis Treatments Affect Bone Matrix Maturation in a Rat Model of Induced Cortical Remodeling

ABSTRACT To test how osteoporosis drugs affect bone matrix maturation during cortical bone remodeling, 72 pregnant rats were switched from a 0.4% to a 0.01% calcium diet at parturition for a 23‐day lactation period. At weaning, eight dams were sacrificed to establish baseline values, while the remaining dams were returned to 0.4% calcium and treated with vehicle (saline), sodium fluoride (NaF), zoledronic acid (ZA), or sclerostin antibody (Scl‐Ab) for either 7 or 28 days (eight animals per group per time point). Femora were examined by μCT, dynamic histomorphometry, Fourier transform infrared imaging, and three‐point bending of notched specimens. Cortical porosity decreased in all groups from baseline to day 28. Intracortical mineralizing surface (MS/BS) and mineral apposition rate (MAR), as well as the mineral‐to‐matrix ratio were unaffected by treatment, but intracortical crystallinity was increased in the ZA group at day 10 compared with vehicle. Cortical area increased in all groups over 28 days mainly because of an addition of bone at the endocortical surface. Endocortical MS/BS did not vary among the groups, but endocortical MAR was suppressed in the NaF group at day 2 and elevated in the Scl‐Ab group at day 4 compared with vehicle. Endocortical mineral‐to‐matrix ratio was increased at days 5 and 10 following NaF treatment and endocortical crystallinity was increased at day 5 following ZA treatment compared with vehicle. Fracture toughness did not differ among the groups. Thus, the treatments affected matrix maturation more strongly at the endocortical then intracortical envelope. In this model of induced remodeling, the bone formation phase is synchronized at multiple sites, facilitating study of the effects of drugs or other bone‐targeting agents on matrix maturation independent of their effects on the initiation of remodeling. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Flaxseed oil ameliorates aging in d ‐galactose induced rats via altering gut microbiota and mitigating oxidative damage

Abstract BACKGROUND Aging causes decreased antioxidant capacity and chronic inflammation and may even elevate cancer risks. Previous studies reported that flaxseed oil (FO) can alleviate age‐related diseases, including improving alcoholic liver disease, atherosclerosis and diabetes. However, whether the intestinal microbiota accountable for this alleviation is still unknown. This study aims to study the antioxidant effects of FO in an aging rat model and the underlying mechanism between the intestinal microbiota and aging. RESULTS Our results presented that serum and liver antioxidant capacities in FO group were up‐regulated, and liver inflammation in FO group was reduced. The 16S rDNA sequencing showed that FO regulated the microbial community, including up‐regulation of four families of Lactobacillus and six families of Clostridium. In addition, FO had also adjusted the relative abundance of several genera such as Ruminococcaceae_UCG‐005 and Prevotella_9 , which may be the key bacteria associated with the aging process. Colonic transcriptome analysis showed that there were 1679 differentially expressed genes (DEGs) in the Model group and the FO group (134 up‐regulated and 1545 down‐regulated). Gene set enrichment analysis (GSEA) revealed FO down‐regulates the expression of the upstream genes Ptprc , Lck , Zap70 , Lat and Lcp2 in the T cell receptor signaling pathway. CONCLUSION In conclusion, FO improved antioxidant capacity and reduced intestinal microbial disturbances caused by aging damage, indicating that dietary FO has the potential to fight aging damage. This study provides a more comprehensive view of dietary intervention to improve aging. © 2022 Society of Chemical Industry.

Sun, Xiaoyan↗
DOE OSTI2026

Bio-distribution and deposition of wildfire smoke chemicals into olfactory bulb and brain of rats after intranasal instillation

Epidemiological and experimental studies suggest wildfire smoke is a potential contributor to neurological dysfunction and associated with neuroinflammation. Using doses comparable to those encountered during intense wildfire events (200-300 μg/m 3 ), we explore the absorption, distribution, metabolism, and elimination (ADME) and pharmacokinetics of representative members of major chemical classes (acid, phenol, PAH, aldehyde) in inhaled wood smoke condensates. Male Sprague Dawley rats were intranasally instilled with smoldering eucalyptus woodsmoke extract (WSE) reconstituted in saline spiked with 14 C-labeled palmitic acid (PA), benzo[a]pyrene (B[a]P), catechol (CAT) or benzaldehyde (BZ). Serum was collected from 5 min to 2 weeks after exposure and tissues were collected at 0.5, 2, 4, 24 h and 2 weeks after exposure. Urine was collected over the 24 h exposure. Tissues were collected, rinsed in PBS and analyzed by accelerator mass spectrometry (AMS) for 14C-labeled chemicals. PA and B[a]P entered circulation slowly, reached maximum concentration (C max ) near 15 ng/mL at 2 h, and had circulating concentrations near 1/3 C max 24 h after exposure. CAT and BZ rapidly entered circulation and were mostly cleared at 2 h. Excess 14 C from all four chemicals was detected in olfactory bulb and brain over the first 24 h but only PA (or its metabolites) was retained in olfactory bulb, brain and kidney at 2 weeks post exposure. All excess 14 C was cleared from the lung at 2 weeks. Metabolite analysis of urine (CAT, BZ and B(a)P) dosed samples did not detect any parent compound. CAT and BZ were rapidly cleared. The slower uptake and clearance of PA or B[a]P or their reactive metabolites when dosed with WSE in brain and olfactory bulb potentially provide greater opportunity for inflammatory response. This study suggests that wildfire smoke chemicals can enter the brain directly from the nasal cavity to the olfactory bulb and via systemic circulation.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2025

Investigating the FLASH Effect in a Rat Brain Organotypic Model With a Novel High-Energy Electron Beam

Ultrahigh dose rate (FLASH) radiation therapy is reported to reduce normal tissue toxicity while maintaining tumor control; however, mechanism(s) remain obscure. To study FLASH mechanisms in brain tissue, we developed a novel experimental platform featuring a specialized high-energy electron linear accelerator, High Intensity Gamma Ray Source (HIGS), paired with an organotypic ex vivo brain metastasis model. We varied interpulse spacing to modulate the mean dose rate (MDR) of our unique 35 MeV electron beam, while maintaining extremely high instantaneous dose rate (IDR). We characterized dosimetry and targeting accuracy of the FLASH beam with film dosimetry. We combined this FLASH beam with an organotypic rat brain slice/breast carcinoma coculture model of brain metastasis to assess effects on normal and neoplastic tissues. Live-cell and bioluminescence imaging demonstrated cancer cell growth effects, whereas normal tissue responses and immune activation were assessed using live-cell imaging, cytokine profiles, and confocal microscopy. Here, we performed comparison experiments with 20 MeV electrons from a Varian clinical linear accelerator (VCLA) using conventional dose rates. The highest IDR of the FLASH beam to date was 20.7 ± 0.6 MGy/s, with maximum MDR of 20.7 MGy/s delivered in 1 pulse of 1 µs duration. Beam targeting was accurate to <1 mm and reproducible. HIGS-FLASH and VCLA dose rates equivalently decreased cancer cell growth. HIGS-FLASH irradiation significantly increased tumor necrosis factor α and fractalkine levels and confocal microscopy revealed distinct changes in microglial morphology slices suggesting microglia activation. Our novel experimental platform produces extremely high dose rates and rapid normal/neoplastic tissue readouts for mechanistic research into the effects of FLASH radiation in the brain. HIGS-FLASH irradiation induces comparable cancer cell growth inhibition but differential effects on cytokines and microglial morphology, suggesting that acute innate immune responses may be involved in FLASH normal tissue effects in the brain.

Kay, Tyler V. [Duke University, Durham, NC (United↗
DOE OSTI2023

Perivascular network segmentations derived from high-field MRI and their implications for perivascular and parenchymal mass transport in the rat brain

A custom segmentation workflow was applied to ex vivo high-field MR images of rat brains acquired following in vivo intraventricular contrast agent infusion to generate maps of the perivascular spaces (PVS). The resulting perivascular network segmentations enabled analysis of perivascular connections to the ventricles, parenchymal solute clearance, and dispersive solute transport within PVS. Numerous perivascular connections between the brain surface and the ventricles suggest the ventricles integrate into a PVS-mediated clearance system and raise the possibility of cerebrospinal fluid (CSF) return from the subarachnoid space to the ventricles via PVS. Assuming rapid solute exchange between the PVS and CSF spaces primarily by advection, the extensive perivascular network decreased the mean clearance distance from parenchyma to the nearest CSF compartment resulting in an over 21-fold reduction in the estimated diffusive clearance time scale, irrespective of solute diffusivity. This corresponds to an estimated diffusive clearance time scale under 10 min for amyloid-beta which suggests that the widespread distribution of PVS may render diffusion an effective parenchymal clearance mechanism. Additional analysis of oscillatory solute dispersion within PVS indicates that advection rather than dispersion is likely the primary transport mechanism for dissolved compounds greater than 66 kDa in the long (> 2 mm) perivascular segments identified here, although dispersion may be significant for smaller compounds in shorter perivascular segments.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue

Subcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training (ExT) and sex on its molecular landscape is not fully established. Utilizing an integrative multi-omics approach, and leveraging data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we show profound sexual dimorphism in the scWAT of sedentary rats and in the dynamic response of this tissue to ExT. Specifically, the scWAT of sedentary females displays -omic signatures related to insulin signaling and adipogenesis, whereas the scWAT of sedentary males is enriched in terms related to aerobic metabolism. These sex-specific -omic signatures are preserved or amplified with ExT. Integration of multi-omic analyses with phenotypic measures identifies molecular hubs predicted to drive sexually distinct responses to training. Overall, this study underscores the powerful impact of sex on adipose tissue biology and provides a rich resource to investigate the scWAT response to ExT.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Effect of Electroacupuncture at Wushu Acupoints of the Cardiopulmonary Meridian on the Autophagy in Rats with Acute Myocardial Ischemia

Wushu acupoints are the five acupoints distributed below the human elbow and knee joint. They are all located on the same meridian and divided into five categories: Jing, Ying, Shu, Jing, and He. It has been shown that electroacupuncture (EA) at Shenmen point of heart meridian can improve acute myocardial ischemia (AMI) early. However, it is still unclear if all the Wushu acupoints of the heart meridian can improve AMI. Hence, this study emphasizes Wushu acupoints of heart meridian, compares them with Wushu acupoints of lung meridian, and studies the therapeutic effect of EA at Wushu acupoints on AMI and its possible mechanism. It also discusses the specificity of the heart meridian to heart disease. The AMI model is established by ligation of the left anterior descending coronary artery. The detection methods like the physiological recorder, TTC staining, ELISA, and so forth were used to determine the ECG, myocardial infarct size, serum myocardial enzymes, and myocardial tissue-related protein expression in rats. The heart rate (HR) and ST segment along with creatine kinase (CK), creatine kinase isoenzymes (CK-MB), lactate dehydrogenase (LDH), and myocardial infarctions increased after the induction with AMI. Furthermore, the expressions of PINK1 and Parkin protein also showed an increase. However, EA at Wushu acupoints in the heart meridian can reverse the above changes, whereas EA at the lung meridian exhibits limited effect. It is depicted that the heart meridian has a relatively specific relationship with the heart in a diseased state.

Zhu, Chao↗
DOE OSTI2020

Comparative genetics of Enterococcus faecalis intestinal tissue isolates before and after surgery in a rat model of colon anastomosis

We have recently demonstrated that collagenolytic Enterococcus faecalis plays a key and causative role in the pathogenesis of anastomotic leak, an uncommon but potentially lethal complication characterized by disruption of the intestinal wound following segmental removal of the colon (resection) and its reconnection (anastomosis). Here we hypothesized that comparative genetic analysis of E. faecalis isolates present at the anastomotic wound site before and after surgery would shed insight into the mechanisms by which collagenolytic strains are selected for and predominate at sites of anastomotic disruption. Whole genome optical mapping of four pairs of isolates from rat colonic tissue obtained following surgical resection (herein named "pre-op" isolates) and then 6 days later from the anastomotic site (herein named "post-op" isolates) demonstrated that the isolates with higher collagenolytic activity formed a distinct cluster. In order to perform analysis at a deeper level, a single pair of E. faecalis isolates (16A pre-op and 16A post-op) was selected for whole genome sequencing and assembled using a hybrid assembly algorithm. Comparative genomics demonstrated absence of multiple gene clusters, notably a pathogenicity island in the post-op isolate. No differences were found in the fsr-gelE-sprE genes (EF1817-1822) responsible for regulation and production of collagenolytic activity. Analysis of unique genes among the 16A pre-op and post-op isolates revealed the predominance of transporter systems-related genes in the pre-op isolate and phage-related and hydrolytic enzyme-encoding genes in the post-op isolate. Despite genetic differences observed between pre-op and post-op isolates, the precise genetic determinants responsible for their differential expression of collagenolytic activity remains unknown.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Transmural Remodeling of Cardiac Microstructure in Aged Spontaneously Hypertensive Rats by Diffusion Tensor MRI

The long-standing high blood pressure (also known as hypertension) overworks the heart. Microstructural remodeling is a key factor of hypertensive heart disease progression. Diffusion tensor magnetic resonance imaging (DT-MRI) is a powerful tool for the rapid noninvasive nondestructive delineation of the cardiomyocyte organization. The spontaneously hypertensive rat (SHR) is a well-established model of genetic hypertension. The goal of this study was to employ high-resolution DT-MRI and the SHR animal model to assess the transmural layer-specific remodeling of myocardial microstructure associated with hypertension. Ex vivo experiments were performed on excised formalin-fixed hearts of aged SHRs (n = 4) and age-matched controls (n = 4). The DT-MRI-derived fractional anisotropy (FA), longitudinal diffusivity (λ L ), transversal diffusivity (λ T ), and mean diffusivity (MD) served as the readout parameters investigated at three transmural zones (i.e., endocardium, mesocardium, and epicardium). The helix angles (HAs) of the aggregated cardiomyocytes and the orientation of laminar sheetlets were also studied. Compared with controls, the SHRs exhibited decreased epicardial FA, while FA changes in the other two transmural regions were insignificant. No substantial differences were observed in the diffusivity parameters and the transmural course of HAs between the two groups. A consistent distribution pattern of laminar sheetlet orientation was not identified for either group. Our findings are in line with the known cellular microstructure from early painstaking histological studies. Biophysical explanations of the study outcomes are provided. In conclusion, our experimental findings indicate that the epicardial microstructure is more vulnerable to high blood pressure leading to more pronounced changes in this region during remodeling. DT-MRI is well-suited for elucidating these alterations. The revealed transmural nonuniformity of myocardial reorganization may shed light on the mechanisms of the microstructure-function relationship in hypertension progression. Our results provide insights into the management of patients with systemic arterial hypertension, thus prevent the progression toward heart failure. The findings of this study should be acknowledged by electromechanical models of the heart that simulate the specific cardiac pathology.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Acute Ozone-Induced Transcriptional Changes in Markers of Oxidative Stress and Glucocorticoid Signaling in the Rat Hippocampus and Hypothalamus Are Sex-Specific

Exposure to a prototypic air pollutant ozone (O 3 ) has been associated with the activation of neuroendocrine stress response along with neural changes in oxidative stress (OS), inflammation, and Alzheimer’s disease-like pathologies in susceptible animal models. We hypothesized that neural oxidative and transcriptional changes induced by O 3 in stress responsive regions are sex-dependent. Male and female adult Long–Evans rats were exposed to filtered air or O 3 for two consecutive days (0.8 ppm, 4 h/day) and brain regions were flash-frozen. Activities of cerebellar OS parameters and mitochondrial complex I, II, and IV enzymes were assessed to confirm prior findings. We assessed transcriptional changes in hypothalamus (HYP) and hippocampus (HIP) for markers of OS, microglial activity and glucocorticoid signaling using qPCR. Although there were no O 3 or sex-related differences in the cerebellar activities of OS and mitochondrial enzymes, the levels of protein carbonyls and complex II activities were higher in females regardless of O 3 . There were no statistical differences in baseline expression of genes related to OS (Cat, Dhcr24, Foxm1, Gpx1, Gss, Nfe2l2, Sod1) except for lower HYP Sod1 expression in air-exposed females than males, and higher HIP Gss expression in O 3 -exposed females relative to matched males. Microglial marker Aif1 expression was higher in O 3 -exposed females relative to males; O 3 inhibited Itgam only in males. The expression of Bdnf in HIP and HYP was inhibited by O 3 in both sexes. Genes related to glucocorticoid signaling (Fkbp4, Fkbp5, Hsp90aa1, Hspa4, nr3c1, nr3c2) showed sex-specific effects due to O 3 exposure. Baseline expression of HIP Fkbp4 was higher in females relative to males. O 3 inhibited Nr3c1 in female HIP and male HYP, but Nr3c2 was inhibited in male HYP. Fkbp4 expression was higher in O 3 -exposed females when compared to matched males, whereas Fkbp5 was expressed at higher levels in both brain regions of males and females. These results indicate that sex-specific brain region responses to O 3 might, in part, be caused by OS and regulation of glucocorticoid signaling.

59 BASIC BIOLOGICAL SCIENCES↗