Age-dependent Responses Research Articles

Ethanol Stimulation of Microglia Release Increases ERK1/2-Dependent Neuronal cPLA2 Activity in Immature Cultured Cortical Preparations.

Ethanol consumption typically begins during adolescence and is associated with age-dependent responses and maladaptive neuronal consequences. Our previous work established the role of a putative signaling cascade involving cytoplasmic phospholipase A2 (cPLA2), arachidonic acid (AA) and novel protein kinase C isoforms in adolescent hypnotic sensitivity. The current study aimed to further delineate this pathway by ascertaining the cellular specificity as well as the upstream activators of cPLA2 using an immature cultured cortical preparation. A threefold increase in cPLA2 was detected within 2min of 100mM ethanol exposure as measured by phosphorylation of serine 505 (Ser505). Increases in cPLA2 activity were further observed to be primarily confined to neuronal cells. Increases in the number of neurons co-expressing cPLA2 Ser505 phosphorylation were prevented by preincubation with an ERK1/2 inhibitor, but not P38 MAPK inhibition. Finally, conditioned media studies were used to determine whether glial cells were involved in the ethanol-induced neuronal cPLA2 activity. Rapid increases in neuronal cPLA2 activity appears to be initiated through ethanol stimulated microglial, but not astrocytic releasable factors. Taken together, these data extend the proposed signaling cascade involved in developmental ethanol responding.

Otolith increment width-based chronologies disclose temperature and density-dependent effects on demersal fish growth

Abstract Climate change and fishing are drastically impacting marine ecosystems. Comprehending the biological consequences of these effects on commercially exploited fish is especially challenging. Here, we developed a 43-year otolith increment width-based growth chronology for one of the most important commercially exploited fish species in the Northeast Atlantic (European hake, Merluccius merluccius). Increasingly complex linear mixed-effects models were used to partition growth variation into intrinsic (age, sex, and age-at-capture) and extrinsic (environmental and biotic variables) factors, allowing age interaction with extrinsic variables to assess age-dependent responses in growth. Our results provided strong evidence that European hake growth is impacted by ocean temperature, namely sea surface temperature and temperature at depth, and species abundance (recruitment), with different responses depending on fish age. We found evidence that increasing ocean temperature could be highly detrimental for species growth especially during the first years of life. We provided insights into the effects of environmental and biotic factors on species growth variation. Such information is key to recognize the sensitivity of European hake growth to climate change, which may contribute to sustainable management policies for this valuable resource.

Avian selenogenome: response to dietary Se and vitamin E deficiency and supplementation

Selenium (Se) is an essential nutrient for humans and all food-producing animal species. Nutritional deficiencies of Se and (or) vitamin E induce exudative diathesis, nutritional pancreatic atrophy, and nutritional muscular dystrophy in chicks. Although these diseases are presumably associated with the need of Se for the synthesis of the 21st amino acid, selenocysteine (Sec, U) in selenoproteins, metabolic functions of the 25 selenoproteins identified in avian species remain largely unknown. This paper reviews regulations of the whole selenogenome and selected selenoproteins by different concentrations and chemical forms of dietary Se and (or) vitamin E in various affected tissues. The avian selenogenome may be divided into 2 groups: responders and non-responders, based on its response to dietary Se and vitamin E changes. Mechanisms for the gene-, tissue-, and age-dependent responses and the correlation with the stress and cell death signaling are explored. Overall, this review intends to link the novel regulation and function of avian selenogenome to the protection by Se against oxidative insults associated with the classical Se/vitamin E deficiency diseases in chicks.

Synergistic Improvement in Children with Cerebral Palsy Who Underwent Double-Course Human Wharton's Jelly Stem Cell Transplantation.

Background Our previous studies confirmed that human Wharton's Jelly stem cell (hWJSC) transplantation improved motor function in children with spastic cerebral palsy (CP). This study investigated the dose-effect relationship between the transplanted cell dosage and efficacy in CP children. Methods CP children who received one- or two-course (four or eight times lumbar puncture, 4 or 8 × 107 hWJSCs) cell therapy were recruited into this study. Assessments of motor function were performed according to scales for gross motor function measurement (GMFM) and fine motor function measurement (FMFM). The measurement data obtained in the two different groups were analyzed by t-test. Univariate repeated measures analysis of variance was used to compare the data obtained at baseline and 6 or 12 months posttransplantation and met the conditions for Mauchly's sphericity test. Results The results for fifty-seven pediatric CP patients (including 35 male and 22 female patients) who completed follow-up showed that gross and fine motor functions improved after cell therapy. Interestingly, the GMFM and FMFM scores in patients who received one course of transplantation were significantly increased at 6 months after treatment. Moreover, another course of transplantation further improved gross and fine motor function in children. The scores for GMFM and FMFM were significantly higher at 6 months posttransplantation than at baseline and showed a linear upward trend. There was no gender difference in GMFM. Interestingly, there was a significant difference between male and female patients in the B and C dimensions of FMFM. These results reveal a gender-related susceptibility to stem cell therapy, especially for movement capability of the upper extremity joint and grasping ability. Similarly, in the group aged ≤3 years old, the improvement observed in dimension A (lying and rolling) of GMFM was nearly exponential and showed a quadratic trend. The results for FMFM were similar to those for GMFM. Moreover, the improvement in motor function was not age dependent. Conclusions In this study, our data collectively reveal that CP children display sex- or age-dependent responses to hWJSC therapy; these results shed light on the clinical utility of this approach in specific populations.

Age-dependent pulmonary reactivity to house dust mite allergen: a model of adult-onset asthma?

Asthma is a heterogeneous disease differentiated by factors like allergen sensitivity, inflammation, sex, and age at onset. The mouse model is widely used to study the early-life development of allergic asthma. However, age-dependent allergen responses later in life remain relatively understudied and lack a widely accepted model. To differentiate age-dependent responses to the ubiquitous house dust mite (HDM), 3- and 9-mo-old female C57BL/6 mice were randomized into two groups each and exposed to HDM or phosphate-buffered saline (control) via intranasal instillation for sensitization and challenge phases. At 24 h after challenge, all mice underwent pulmonary function testing and methacholine challenge. Bronchoalveolar lavage fluid (BALF) was collected for assessment of cell differentials, and right lung lobes were fixed, sectioned, and stained for histopathology and immunohistochemistry. Both age groups demonstrated strong inflammatory/allergic responses to HDM exposure. However, only 9-mo-old HDM-exposed mice demonstrated significant airway hyperresponsiveness compared with age-matched controls. These HDM-exposed mice also had 1) statistically significant increases in tissue bronchiolitis, perivasculitis, and BALF neutrophilia relative to their younger counterparts and 2) significantly increased extent of immunostaining compared with all other groups. This study presents a potential model for adult-onset asthma, focusing specifically on the atopic, perimenopausal female phenotype. Our findings suggest that lung function declines with age and that the inflammatory profile of this adult subgroup is a mixed, rather than a simple, atopic, Th2 response. This model may enhance our understanding of how age influences the development of asthmic-like symptoms in older subgroups.

Site and age-dependent responses of Picea abies growth to climate variability

Knowledge about spatiotemporal variability of climate change effect on tree-ring width (TRW) and crown condition is essential to optimize the modelling of future forest ecosystem responses to the changing climate. Geographical differences in the climate–growth relationship are a reflection of the regional climatic conditions mainly. In this study, 175 Picea abies trees from the north-western edge of its geographical distribution in Central Norway were evaluated with respect to geographical and age-dependent differences during the common period of 1950–2015. The results showed that the most significant positive correlations between TRW and the current June temperature were unstable although the temperature increased. The correlations suddenly started to decrease (regardless of the site placement and tree age) at the beginning of the 1990s, but subsequently unexpectedly increased in the 2010s. The superposed epoch analysis revealed longer TRW regeneration of the southern plots (except over-mature trees) after negative pointer years compared to the northern plots. Previous summer temperature and related physiological processes (cone crops, storage of nutrients, etc.) significantly negatively affected P. abies growth in the current year. Additionally, our results showed that the selection of the chronology version (standard or residual) significantly affects the resulting correlations and thus must be carefully considered in dendroclimatological studies. Our main outputs can contribute to better understanding of the climate–growth relationship variability and general prediction of the radial growth.

Abstract # 2049 Age dependent hypothalamic and pituitary responses to novel environment stress or lipopolysaccharide in rats

Previously, we have shown that nuclear factor interleukin (NF-IL)6 can be used as an activation marker for inflammatory lipopolysaccharide (LPS)-induced and psychological novel environment stress (NES) in the rat brain. Here, we aimed to investigate age-dependent changes of hypothalamic and pituitary responses to NES (cage switch) or LPS (100 μg/kg) in two and 24 months old rats. In the old rats, telemetric recording showed enhanced and prolonged NES-induced hyperthermia, which was accompanied by increased hypothalamic IL-6 mRNA expression and overall higher plasma corticosterone levels while corticotropin-releasing hormone mRNA-expression was only increased in young rats 90min after NES. Immunohistochemical analysis revealed a significant upregulation of NF-IL6-positive cells in the pituitary after NES or LPS-injection with higher numbers of NF-IL6 or NF-IL6-CD68-positive cells in the median eminence (LPS) or posterior pituitary (NES) of old rats compared to the young counterparts. Moreover, LPS-treatment significantly upregulated the secretion of the cytokines IL-6 and TNF α into supernatants of primary cell cultures of the anterior pituitary. Incubation with IL-6 and IL-10 antibodies prior to LPS-stimulation led to a robust decrease of IL-6- and an increase of TNF α -production by the pituitary cells in young but not in old rats. Overall, we show a prolonged hyperthermic and inflammatory response in aged animals to LPS and NES, which is linked to dysregulated pituitary cytokine interactions and modified brain cell activation (NF-IL6) in the hypothalamus-pituitary-adrenal axis.

Developmental differences in microglia morphology and gene expression during normal brain development and in response to hypoxia-ischemia

BackgroundNeuroinflammation plays an important role in ischemic brain injury and recovery, however the interplay between brain development and the neuroinflammatory response is poorly understood. We previously described age-dependent differences in the microglial response and the effect of microglial inhibition. Here we investigate whether age-dependent microglial responses may be related to pre-injury developmental differences in microglial phenotype. MethodsMeasures of microglia morphology were quantified using semi-automated software analysis of immunostained sections from postnatal day 2 (P2), P9, P30 and P60 mice using IMARIS. Microglia were isolated from P2, P9, P30 and P60 mice, and expression of markers of classical and alternative microglial activation was assessed, as well as transforming growth factor beta (TGF-β) receptor, Serpine1, Mer Tyrosine Kinase (MerTK), and the suppressor of cytokine signaling (SOCS3). Hypoxia-ischemia (HI) was induced in P9 and P30 mice using unilateral carotid artery ligation and exposure to 10% oxygen for 50 min. Microglia morphology and microglial expression of genes in the TGF-β and MerTK pathways were determined in ipsilateral and contralateral hippocampus. ResultsA progressive and significant increase in microglia branching morphology was seen in all brain regions from P2 to P30. No consistent classical or alternative activation profile was seen in isolated microglia. A clear transition to increased expression of TGF-β and its downstream effector serpine1 was seen between P9 and P30. A similar increase in expression was seen in MerTK and its downstream effector SOCS3. HI resulted in a significant decrease in branching morphology only in the P9 mice, and expression of TGF-β receptor, Serpine1, MerTK, and SOCS3 were elevated in P30 mice compared to P9 post-HI. Conclusion: Microglia maturation is associated with changes in morphology and gene expression, and microglial responses to ischemia in the developing brain differ based on the age at which injury occurs.

Age-dependent responses in cellular mechanisms and essential oil production in sweet Ferula assafoetida under prolonged drought stress

ABSTRACT The effect of environmental conditions at different developmental ages on the vegetative growth phase was investigated in sweet Ferula assa-foetida in order to identify the defensive mechanisms and essential oil production. Younger plants had more potential for producing the essential oil. Sulfur and sesquiterpenoid compounds were detected as the main groups of components. Monoterpene production was limited to camphene that particularly appeared in older plants. Thiourea as the main sulfur-containing component in fresh tissues helped plants to tolerate abiotic stresses due to scavenging activity of reactive oxygen species (ROS). Three isoforms of SOD and one isoform of catalase were identified in the plants subjected to environmental stresses. The significant enhancement in protein level and reduction in H2O2 level during the period of growth with strong induction in antioxidant enzymes’ activities in older plants indicated that they have more functional defensive mechanisms in comparing to younger plants.

Steroid signaling mediates longevity responses to the eat-2 genetic model of dietary restriction in Caenorhabditis elegans

Dietary restriction (DR) extends lifespan in a wide range of model organisms, including Caenorhabditis elegans. It is an interesting but yet to be addressed question whether hormones serve as a systemic mechanism that mediates this longevity response. We identified a requirement for steroid signaling in lifespan extension induced by DR, by studying two members of the conserved 3β-hydroxysteroid dehydrogenase (3β-HSD) family, HSD-2 and HSD-3. Specifically, we found that lifespan extension in the eat-2 genetic model of DR is completely suppressed by a deletion mutant of hsd-2. This suppression is independent of the decreased brood size and prolonged egglay timing of eat-2, as neither was affected by hsd-2, suggesting that the hsd-2-mediated steroid signal regulates longevity without influencing reproduction. Furthermore, hsd-2 suppressed the ability of eat-2 to resist acute heat shock; stress, as measured by survival after recovery, but only later in life (day 7 and day; 13 adults). This indicates a role for hsd-2 in age-dependent responses to DR, consistent with; hsd-2 expression, which is primarily in adults. Since hsd-2 did not affect DR-induced heat shock resistance in day 1 adults, we hypothesized that hsd-3, which is only expressed in larvae, might be functioning in that role. Indeed, we found that while a deletion mutant of hsd-3 does not appear to affect eat-2 overall lifespan, it completely suppressed its ability to resist heat shock stress as day 1 adults. Therefore, although both hsd-2 and hsd-3 contribute to stress resistance in eat-2 adults, only hsd-2 impacts lifespan, as though steroid signaling in older eat-2 adults is more important for lifespan extension than steroid signaling in larvae and young adults. Taken together, our results indicate that steroid signaling through these two steroidogenic enzymes, active at distinct times during the worm lifespan, is vital for the health and longevity conferred by DR.

Age-dependent migratory behavior of human endothelial cells revealed by substrate microtopography

Cell migration is part of many important in vivo biological processes and is influenced by chemical and physical factors such as substrate topography. Although the migratory behavior of different cell types on structured substrates has already been investigated, up to date it is largely unknown if specimen's age affects cell migration on structures. In this work, we investigated age-dependent migratory behavior of human endothelial cells from young (≤ 31 years old) and old (≥ 60 years old) donors on poly(dimethylsiloxane) microstructured substrates consisting of well-defined parallel grooves. We observed a decrease in cell migration velocity in all substrate conditions and in persistence length perpendicular to the grooves in cells from old donors. Nevertheless, in comparison to young cells, old cells exhibited a higher cell directionality along grooves of certain depths and a higher persistence time. We also found a systematic decrease of donor age-dependent responses of cell protrusions in orientation, velocity and length, all of them decreased in old cells. These observations lead us to hypothesize a possible impairment of actin cytoskeleton network and affected actin polymerization and steering systems, caused by aging.

Age-related climate sensitivity in Pinus Edulis at Dinosaur National Monument, Colorado, USA

The influence of tree age on climate sensitivity is of central importance in dendrochronology. Recent research has highlighted the disparate nature of age-dependent growth responses across species and geographic locations. We compared growth sensitivity and the influence of climate in Pinus edulis (Piñon) of varying ages at Dinosaur National Monument (DINO, northwestern Colorado, USA. Piñon is a particularly good species for this study because of its long life-span and climate sensitivity, and the DINO site is at the northern extreme of the current distribution. We evaluated changes in climate-growth relationships in piñon using total ring-width measurements and running averages of chronology statistics, mean sensitivity (MS) and coefficient of variation (CV), and we investigated growth response to climate variability as trees age. These measures indicated initial low growth sensitivity, increasing as trees reached mid-life stages, approximately 200–250 years, then relatively constant sensitivity from 250-800+ years. First order partial auto correlation (PAC1) declined throughout the life stages of piñon at DINO. The trend in declining autocorrelation leads to higher MS values in the older age classes. Greater year to year variation indicates less persistence in the study population, hence lower autocorrelation.We investigated the degree to which this relationship could be explained by the summer Palmer Drought Severity Index (PDSI) and whether this relationship varied with tree age. The strength of the tree-ring growth response to PDSI was at a maximum during the first two centuries of growth (R2 = 0.54). between two and six centuries (R2 = 0.48), after which we detected a decline in the sensitivity of tree growth to PDSI with increasing age (R2 = 0.41). This study adds to the literature on age-related climate sensitivity in trees; our findings indicate that age-related changes in climate-tree-ring growth responses should be considered when climate variables are reconstructed from tree-ring width chronologies, and specifically from Pinus edulis.

Metabolism and Redox Signaling in Brain Aging

A decrease in energy metabolism is associated with brain aging, which was assessed in terms of a coordinated metabolic triad encompassed by mitochondria, insulin signaling (IIS), and JNT ((c-Jun N-terminal kinase) signaling. Impairment of these coordinated responses leads to the cognitive decline that occurs with aging and neurodegenerative disorders. The complexity of the antagonism and cross-talk between IIS- and JNT (signaling and how they converge on mitochondrial function underscores the significance of an insulin resistance state. The hypometabolic state inherent in brain aging, a mouse model of Alzheimer's disease, and high-fat diet-induced obesity was accompanied by decreased brain glucose uptake, an imbalance between IIS- and JNT (signaling, decreased rate of glycolysis and flux of metabolites to the TCA cycle, and diminished synaptic plasticity. These effects are not cell specific, for astrocytes developed an age-dependent energy phenotype (increased mitochondrial oxidative metabolism and biogenesis) and augmented responses to inflammatory cytokines. In most of the models described above, the hypometabolic state was rescued by treatment with lipoic acid, likely through a thiol/disulfide mechanism, which resulted largely in improved IIS and in synaptic plasticity.

Age-dependent biologic response to orthodontic forces.

Orthodontic tooth movement results from increased inflammation and osteoclast activation. Since patients of all ages now routinely seek orthodontics treatment, we investigated whether age-dependent biologic responses to orthodontic force correlate with the rate of tooth movement. We studied 18 healthy subjects, adolescents (11-14years) and adults (21-45years), with Class II Division 1 malocclusion requiring 4 first premolar extractions. Canines were retracted with a constant force of 50cN. Gingival crevicular fluid was collected before orthodontic treatment and at days 1, 7, 14, and 28 after the canine retraction. Cytokine (IL-1β, CCL2, TNF-α) and osteoclast markers (RANKL and MMP-9) were measured using antibody-based protein assays. Pain and discomfort were monitored with a numeric rating scale. The canine retraction rate was measured from study models taken at days 28 and56. Although the cytokine and osteoclast markers increased significantly in both age groups at days 1, 7, and 14, the increases were greater in adults than in adolescents. Interestingly, the rate of tooth movement in adults was significantly slower than in adolescents over the 56-day study period. Adults also reported significantly more discomfort and pain. Age is a significant variable contributing to the biologic response to orthodontic tooth movement. Adults exhibited a significantly higher level of cytokine and osteoclasts activity but, counterintuitively, had a significantly slower rate of tooth movement.

Age-Dependent Developmental Response to Temperature: An Examination of the Rarely Tested Phenomenon in Two Species (Gypsy Moth (Lymantria dispar) and Winter Moth (Operophtera brumata)).

The pervading paradigm in insect phenology models is that the response to a given temperature does not vary within a life stage. The developmental rate functions that have been developed for general use, or for specific insects, have for the most part been temperature-dependent but not age-dependent, except where age is an ordinal variable designating the larval instar. Age dependence, where age is a continuous variable, is not often reported (or investigated), and is rarely included in phenology models. I provide a short review of the seldom-investigated phenomenon of age dependence in developmental response to temperature, and compare the derivation of the winter moth egg phenology model by Salis et al. to the derivation of another egg phenology model with age-dependent responses to temperature I discuss some probable reasons for the discrepancies (acknowledged by Salis et al.) between modelled and observed developmental rates of the winter moth, and discuss the contribution that geographically robust phenology models can make to estimates of species distributions.

Insular cortex mediates approach and avoidance responses to social affective stimuli.

Social animals detect the affective states of conspecifics and utilize this information to orchestrate social interactions. In a novel social affective preference text in which experimental adult male rats could interact with either naive or stressed conspecifics, the experimental rats either approached or avoided the stressed conspecific, depending upon the age of the conspecific. Specifically, experimental rats approached stressed juveniles but avoided stressed adults. Inhibition of insular cortex, which is implicated in social cognition, and blockade of insular oxytocin receptors disrupted the social affective behaviors. Oxytocin application increased intrinsic excitability and synaptic efficacy in acute insular cortex slices, and insular oxytocin administration recapitulated the behaviors observed toward stressed conspecifics. Network analysis of Fos immunoreactivity in 29 regions identified functional connectivity between insular cortex, prefrontal cortex, amygdala and the social decision-making network. These results implicate insular cortex as a key component in the circuit underlying age-dependent social responses to stressed conspecifics.

Molecular and functional signatures in a novel Alzheimer\u2019s disease mouse model assessed by quantitative proteomics

BackgroundAlzheimer’s disease (AD), the most common neurodegenerative disorder, is characterized by the deposition of extracellular amyloid plaques and intracellular neurofibrillary tangles. To understand the pathological mechanisms underlying AD, developing animal models that completely encompass the main features of AD pathologies is indispensable. Although mouse models that display pathological hallmarks of AD (amyloid plaques, neurofibrillary tangles, or both) have been developed and investigated, a systematic approach for understanding the molecular characteristics of AD mouse models is lacking.MethodsTo elucidate the mechanisms underlying the contribution of amyloid beta (Aβ) and tau in AD pathogenesis, we herein generated a novel animal model of AD, namely the AD-like pathology with amyloid and neurofibrillary tangles (ADLPAPT) mice. The ADLPAPT mice carry three human transgenes, including amyloid precursor protein, presenilin-1, and tau, with six mutations. To characterize the molecular and functional signatures of AD in ADLPAPT mice, we analyzed the hippocampal proteome and performed comparisons with individual-pathology transgenic mice (i.e., amyloid or neurofibrillary tangles) and wild-type mice using quantitative proteomics with 10-plex tandem mass tag.ResultsThe ADLPAPT mice exhibited accelerated neurofibrillary tangle formation in addition to amyloid plaques, neuronal loss in the CA1 area, and memory deficit at an early age. In addition, our proteomic analysis identified nearly 10,000 protein groups, which enabled the identification of hundreds of differentially expressed proteins (DEPs) in ADLPAPT mice. Bioinformatics analysis of DEPs revealed that ADLPAPT mice experienced age-dependent active immune responses and synaptic dysfunctions.ConclusionsOur study is the first to compare and describe the proteomic characteristics in amyloid and neurofibrillary tangle pathologies using isobaric label-based quantitative proteomics. Furthermore, we analyzed the hippocampal proteome of the newly developed ADLPAPT model mice to investigate how both Aβ and tau pathologies regulate the hippocampal proteome. Because the ADLPAPT mouse model recapitulates the main features of AD pathogenesis, the proteomic data derived from its hippocampus has significant utility as a novel resource for the research on the Aβ-tau axis and pathophysiological changes in vivo.

Age-dependent sympathetic neural responses to ß1 selective beta-blockade in untreated hypertension-related tachycardia

Background: Elevated heart rate (HR) increases cardiovascular morbidity and mortality in hypertension. The impact of beta-blockers on patient prognosis in hypertension is controversial. This study examined the age-related effects of betaxolol on HR, muscle sympathetic nerve activity (MSNA), blood pressure (BP) and sympathovagal balance in untreated males with hypertension and tachycardia.Methods: Ten young (age 26 ± 1 years) and seven older (age 50 ± 4 years) males underwent measurement of BP, HR, HR variability (Poincare plot) and MSNA before and after 8 weeks treatment with betaxolol at the initial starting dose of 10 mg/day, which was increased to 20 mg/day once daily after 4 weeks in all subjects.Results: In younger subjects, betaxolol decreased systolic BP (−13 ± 4 mm Hg, p = .01) and HR (−29 ± 4 bpm, p < .001) but not MSNA (3 ± 3 burst/min., p = 0.47) after 8 weeks. In older subjects a pronounced reduction in BP (−27 ± 7, p = .007) was accompanied by a significant decrease in MSNA (−13 ± 5 burst/min., p < .05) and HR (−17 ± 4 bpm, p = .002). SD1/SD2 ratio of Poincare plot increased in younger (0.36 ± 0.03 vs 0.51 ± 0.05, p = .004), but not in older (0.43 ± 0.08 vs 0.54 ± 0.12, p = .50) subjects.Conclusion: Autonomic neural responses to betaxolol are age-dependent in hypertension-related tachycardia. Betaxolol reduces sympathetic drive to the heart, but not to the peripheral vessels confirming the contribution of augmented cardiac sympathetic activity to disease pathophysiology in younger adults. In older hypertensives, the sympathovagal balance is not influenced by betaxolol. The paradoxical reduction in MSNA despite lowering of BP and HR in older patients may suggest age-related functional decrements in autonomic control and/or inhibitory effects of betaxolol on the central nervous system.

Cross-sectional area of the murine aorta linearly increases with increasing core body temperature

Purpose: The cardiovascular (CV) system plays a vital role in thermoregulation. To date, the response of core vasculature to increasing core temperature has not been adequately studied in vivo. Our objective was to non-invasively quantify the arterial response in murine models due to increases in body temperature, with a focus on core vessels of the torso and investigate whether responses were dependent on sex or age.Methods: Male and female, adult and aged mice were anaesthetised and underwent magnetic resonance imaging (MRI). Data were acquired from the circle of Willis (CoW), heart, infrarenal aorta and peripheral arteries at core temperatures of 35, 36, 37 and 38 °C (±0.2 °C).Results: Vessels in the CoW did not change. Ejection fraction decreased and cardiac output (CO) increased with increasing temperature in adult female mice. Cross-sectional area of the aorta increased significantly and linearly with temperature for all groups, but at a diminished rate for aged animals (p < 0.01; male and female: adult, 0.019 and 0.024 mm2/°C; aged, 0.017 and 0.011 mm2/°C). Aged male mice had a diminished response in the periphery (% increase in femoral artery area from 35 to 38 °C, male and female: adult, 67 and 65%; aged, 0.1 and 57%).Conclusion: Previously unidentified increases in aortic area due to increasing core temperature are biologically important because they may affect conductive and convective heat transfer. Leveraging non-invasive methodology to quantify sex and age dependent vascular responses due to increasing core temperature could be combined with bioheat modelling in order to improve understanding of thermoregulation.

Age-Dependent Responses of Brain Myelin Integrity and Behavioral Performance to Radiation in Mice.

Radiation therapy is widely used to treat primary and metastatic brain tumors, but it may also lead to delayed neurological complications. Oligodendrocytes in the central nervous system produce myelin, and myelin integrity becomes highly vulnerable after brain irradiation. In this study, mice at different developmental stages were used to test the age-dependent sensitivity of myelin formation and maintenance, as well as behavioral performance after whole-brain irradiation (WBI). Mice at postnatal days 21 and 28 and at 2 months received a single dose of 25 Gy WBI. Behavioral tests for general locomotor activity and motor coordination revealed an age-dependent response after WBI. Quantitative observation revealed a sharp decrease in the number of oligodendrocytes beginning at day 1 after WBI, which recovered during different observation intervals in white matter and gray matter in mice of different ages. Myelin basic protein (MBP) staining revealed disparate quantities in an age- and brain-region-dependent pattern between groups after WBI, which was confirmed using Black-Gold staining. In summary, the response to radiation in mice of different ages provided insight into the potential of oligogenesis in microenvironments at respective stages of myelin regeneration, which may reduce central nervous system impairment and optimize the prognosis after radiation treatment.