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Rebecca A Johnson

Publications and source records attributed to Rebecca A Johnson.

14 recordsLinked to original sources
PubMed2006

Genome-wide atlas of gene expression in the adult mouse brain.

Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of approximately 20,000 genes in the adult mouse brain. Data were generated using automated high-throughput procedures for in situ hybridization and data acquisition, and are publicly accessible online. Newly developed image-based informatics tools allow global genome-scale structural analysis and cross-correlation, as well as identification of regionally enriched genes. Unbiased fine-resolution analysis has identified highly specific cellular markers as well as extensive evidence of cellular heterogeneity not evident in classical neuroanatomical atlases. This highly standardized atlas provides an open, primary data resource for a wide variety of further studies concerning brain organization and function.

Animals↗
PubMed2005

Respiratory plasticity after perinatal hypercapnia in rats.

Environmental conditions during early life may have profound effects on respiratory control development. We hypothesized that perinatal hypercapnia would exert lasting effects on the mammalian hypercapnic ventilatory response, but that these effects would differ between males and females. Rats were exposed to 5% CO2 from 1 to 3 days before birth through postnatal week 2 and ventilation was subsequently measured by whole-body plethysmography. In both male and female rats exposed to perinatal hypercapnia, a rapid, shallow breathing pattern was observed for the first 2 weeks after return to normocapnia, but ventilation was unchanged. Acute hypercapnic ventilatory responses (3% and 5% CO2) were reduced 27% immediately following perinatal hypercapnia, but these responses were normal after 2 weeks of recovery in both sexes and remained normal as adults. Collectively, these data suggest that perinatal hypercapnia elicits only transient respiratory plasticity in both male and female rats. This plasticity appears similar to that observed after chronic hypercapnia in adult animals and, therefore, is not unique to development.

Age Factors↗
PubMed2003

BDNF is necessary and sufficient for spinal respiratory plasticity following intermittent hypoxia.

Intermittent hypoxia causes a form of serotonin-dependent synaptic plasticity in the spinal cord known as phrenic long-term facilitation (pLTF). Here we show that increased synthesis of brain-derived neurotrophic factor (BDNF) in the spinal cord is necessary and sufficient for pLTF in adult rats. We found that intermittent hypoxia elicited serotonin-dependent increases in BDNF synthesis in ventral spinal segments containing the phrenic nucleus, and the magnitude of these BDNF increases correlated with pLTF magnitude. We used RNA interference (RNAi) to interfere with BDNF expression, and tyrosine kinase receptor inhibition to block BDNF signaling. These disruptions blocked pLTF, whereas intrathecal injection of BDNF elicited an effect similar to pLTF. Our findings demonstrate new roles and regulatory mechanisms for BDNF in the spinal cord and suggest new therapeutic strategies for treating breathing disorders such as respiratory insufficiency after spinal injury. These experiments also illustrate the potential use of RNAi to investigate functional consequences of gene expression in the mammalian nervous system in vivo.

Animals↗
PubMed2003

Exercise-induced changes in hippocampal brain-derived neurotrophic factor and neurotrophin-3: effects of rat strain.

We tested the hypothesis that exercise-induced changes in hippocampal brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) differ among rat strains exhibiting a range of voluntary wheel running activity. Four strains (Sprague-Dawley, Brown Norway, Dark Agouti and PVG) were given access to running wheels (1 or 7 nights). Over 7 nights, the average distance run per night was higher in PVG versus other strains, and higher in Brown Norway versus Sprague-Dawley rats. Hippocampal BDNF concentrations in sedentary rats were higher in PVG versus Sprague-Dawley rats. When data from all strains were combined, BDNF levels increased with 7 nights of wheel running and were positively correlated to the previous night distance run. Sedentary hippocampal NT-3 levels were not different between rat strains, but decreased with 7 nights of wheel access; NT-3 was negatively correlated with previous night distance run. There were no differences between strains in the correlation between distance run and BDNF or NT-3 levels. Although exercise decreases hippocampal NT-3, strain does not alter NT-3 levels. In contrast, BDNF levels increase with exercise and basal levels differ between strains, possibly due to strain differences in spontaneous activity.

Animals↗
PubMed2003

Free fatty acids modulate intermembrane trafficking of cholesterol by increasing lipid mobilities: novel 13C NMR analyses of free cholesterol partitioning.

Cholesterol and free fatty acids in membranes modulate major biological processes, and their cellular metabolism and actions are often coordinately regulated. However, effects of free fatty acid on cholesterol-membrane interactions have proven difficult to monitor in real time in intact systems. We developed a novel (13)C NMR method to assess effects of free fatty acids on molecular interactions of cholesterol within--and transfer between--model membranes. An important advantage of this method is the ability to acquire kinetic data without separation of donor and acceptor membranes. Large unilamellar phospholipid vesicles (LUV) with phosphatidylcholine/cholesterol ratios of 4:1 served as cholesterol donors. Small unilamellar vesicles (SUV) made with phosphatidylcholine were acceptors. The (13)C(4)-cholesterol peak is narrow in SUV, but very broad in LUV, spectra; the increase in intensity of this peak over time monitored transfer. Oleic acid and other long chain free fatty acids [saturated (C12-18) and unsaturated (C18)] dose-dependently increased mobilities of lipids in LUV (phospholipid and cholesterol) and cholesterol transfer rates, whereas short (C8-10) and very long (C24) chain free fatty acids did not. Decreasing pH from 7.4 to 6.5 (+/-oleic acid) had no effect on cholesterol transfer, and 5 mol % fatty acyl-CoAs increased transfer rates, demonstrating greater importance of the fatty-acyl tail over the headgroup. In LUV containing sphingomyelin, transfer rates decreased, but the presence of oleic acid increased transfer 1.3-fold. These results demonstrate free fatty acid-facilitated cholesterol movement within and between membranes, which may contribute to their multiple biological effects.

Biological Transport↗
PubMed2002

Selective uptake from LDL is stimulated by unsaturated fatty acids and modulated by cholesterol content in the plasma membrane: role of plasma membrane composition in regulating non-SR-BI-mediated selective lipid transfer.

We previously reported that unsaturated fatty acids stimulated low-density lipoprotein (LDL) particle uptake in J774 macrophages by increasing LDL receptor activity. Since free fatty acids (FFA) also change plasma membrane properties, a putative cholesteryl ester (CE) acceptor for selective uptake (SU), we questioned the ability of FFA to modulate SU from LDL. Using [(3)H]cholesteryl ether/(125)I-LDL to trace CE core and whole particle uptake, we found that oleic acid and eicosapentaenoic acid, but not saturated stearic acid, increased SU by 30% over control levels. An ACAT inhibitor, Dup128, abolished FFA effects on SU, indicating that increased SU by FFA was secondary to changes in cell-free cholesterol (FC). Consistent with these observations, ACAT inhibition increased cell FC and reduced LDL SU by half. The important role of plasma membrane composition was further demonstrated in that beta-cyclodextrin- (beta-CD-) mediated FC removal from the plasma membrane increased SU from LDL and was further stimulated by U18666A, a compound that inhibits FC transport between lysosomes and the plasma membrane. In contrast, cholesterol-saturated beta-CD markedly reduced LDL SU. In contrast to LDL SU, oleic acid, ACAT inhibition, U18666A, or beta-CD had no effects on HDL SU. Moreover, HDL SU was inhibited by antimouse SR-BI antibody by more than 50% but had little effect on LDL SU. In C57BL/6 mice fed a high fat diet, plasma FFA levels increased, and SU accounted for an almost 4-fold increased proportion of total cholesterol delivery to the arterial wall. Taken together, these data suggest that LDL SU is mediated by pathways independent of SR-BI and is influenced by plasma membrane FC content. Moreover, in conditions where elevated plasma FFA occur, SU from LDL can be an important mechanism for cholesterol delivery in vivo.

Androstenes↗
PubMed2002

Chronic cervical spinal sensory denervation reveals ineffective spinal pathways to phrenic motoneurons in the rat.

We hypothesized that pretreatment with chronic cervical dorsal rhizotomy (CDR; C(3)-C(6)) would reveal ineffective crossed spinal pathways to phrenic motoneurons. Anesthetized CDR (1 week post-rhizotomy) and control rats were spinally hemisected at C(2), and phrenic potentials were evoked by stimulating the ventrolateral funiculus contralateral and rostral to hemisection. Phrenic potentials contralateral to the stimulating electrode were evoked at lower stimulus currents (CDR=640 +/- 46 microA; control=900 +/- 50 microA; P<0.05) and potential amplitude was significantly greater in CDR versus control rats (P<0.05). The serotonin receptor antagonist methysergide (4 mg/kg, i.v.) had no effect on the crossed phrenic potential amplitude (91+/-17% of control at 800 microA; P>0.05). Thus, CDR enhances crossed phrenic pathways but serotonin receptor activation is not necessary to maintain this effect.

Animals↗
PubMed2002

Older Latinos, pets, and health.

The majority of thefindings regarding pet ownership, interaction, and the human-animal bond have involved only Caucasians or have included other ethnic group members only incidentally. The extent to which older adultsfrom other ethnic groups may benefitfrom pet ownership and interaction is unclear. If the benefits of human-animal interaction are to be used effectively in promoting health and preventing illness, it is necessary to identify the "boundaries" of effectiveness for this interaction across various populations. The present study is an initial effort at describing one ethnic minority group, Latino pet owners, the extent of their relationships with their pet, and the extent to which these relationships may be beneficial in facilitating health. Twenty-four Latinos over age 50 were studied and are described in terms of their demographic characteristics, relationships with their pets, health, and exercise practices. The findings suggest that the participants were very devoted to their pets, had been involved with pets since childhood, and viewed themselves as healthy.

Aging↗
PubMed2002

Animal-assisted interventions research: issues and answers.

Animal visitation programs have been used in a wide variety of clinical settings with predominantly positive outcomes reported anecdotally. However, there is also a growing body of research investigating the effects of these interventions. Developing and conducting rigorous studies of animal interventions can be a complex and challenging process, The purpose of this article is to identify and discuss several issues arising with this type of research and to posit suggestions for avoiding pitfalls.

Aged↗
PubMed2001

Unsaturated fatty acid-mediated decreases in sterol regulatory element-mediated gene transcription are linked to cellular sphingolipid metabolism.

A major physiological feedback mechanism of cholesterol in transcription of a number of lipid metabolism-related genes is mediated by sterol regulatory elements (SREs) and their binding proteins (SREBPs). Polyunsaturated free fatty acids alone, as well as synergistically with sterols, decrease SRE-mediated gene expression up to 80% in a dose-dependent manner by decreasing levels of the active transcription factor SREBP. We investigated potential mechanisms for this effect. We hypothesized that free fatty acids reduce SREBP-mediated gene transcription by increasing intracellular cholesterol content through the hydrolysis of cellular sphingomyelin, which has a high affinity for free cholesterol. We also questioned whether the lipid second messenger ceramide, a product of sphingomyelin hydrolysis, can decrease SRE-mediated gene transcription. First we investigated the effect of fatty acids on sphingomyelin hydrolysis. Incubation of [(3)H]choline-labeled cells with unsaturated (but not saturated) fatty acids induced hydrolysis of [(3)H]choline-labeled sphingomyelin. Also, incubation of cell extracts from fatty acid-treated cells with [(3)H]sphingomyelin increased generation of [(3)H]ceramide compared with control cells in vitro. We found that addition of ceramide analogs alone and additively with fatty acids decreased SRE expression and that ceramide analogs reduced levels of the transcriptionally active forms of SREBP-1 and SREBP-2. Increasing intracellular ceramide levels by exogenous sphingomyelinase or inhibition of ceramidase decreased SRE-mediated gene expression. None of the above conditions induced apoptosis. Incubation with U18666A, a compound that inhibits intracellular cholesterol movement, increased SRE-mediated gene transcription. C(2)-ceramide abrogated the effect of U18666A on SRE-mediated gene transcription, suggesting cholesterol-independent regulation of SREBP. We provide evidence that sphingomyelin hydrolysis and intermediates of sphingomyelin metabolism (in addition to cholesterol and fatty acids) contribute to regulation of SRE-mediated gene transcription.

Animals↗
PubMedDate not supplied

Evaluating functional activity in older Thai adults.

The purpose of this study was to translate the original English version of the Self-Efficacy and Outcome Expectations Scales for Exercise and Functional Activity and to establish their reliability in older Thai adults in geriatric rehabilitation. This study used a correlational design with repeated measures. Reliability of the Self-Efficacy for Exercise Scale (SEES), the Self-Efficacy for Functional Activity Scale (SEFAS), the Outcome Expectations for Exercise Scale (OEES), and the Outcome Expectations for Functional Activity Scale (OEFAS) developed by Resnick was measured in 20 older adults aged 60 years or older after hip or knee replacement or another orthopedic surgery of their lower extremity. All scales were translated into Thai and back translated into English according to the process described by Marin and Marin. The instruments were administered twice--the 1st and 2nd day in the participants' geriatric rehabilitation program (i.e., the 4th and 5th postoperative day). Results indicated that there was sufficient evidence for internal consistency of the SEES, SEFAS, OEES, and OEFAS with alpha coefficients of 0.84, 0.86, 0.70, and 0.86 respectively. Test-retest reliability of the tools was also demonstrated with Spearman correlation coefficients of 0.84 for the SEES, 0.87 for the SEFAS, 0.61 for the OEES, and 0.54 for the OEFAS. The findings from this study provide important information for instrument adaptation and the applicability of these scales for further studies of older Thai adults.

Activities of Daily Living↗
PubMedDate not supplied

Effectiveness of a behavioral change intervention in Thai elders after knee replacement.

BACKGROUND: After total knee replacement, elders need an effective intervention to change exercise and physical activity behavior. OBJECTIVES: This study examined the effects of a behavioral change intervention (BCI) on self-efficacy and outcome expectations for exercise and functional activity, physical activity participation, and physical performance of older adults. METHODS: The study was based on the social cognitive theory (SCT), with a longitudinal quasi-experimental, pretest-posttest control group design. Sixty-three Thai elders undergoing knee replacement surgery were studied. The experimental group received a BCI based on SCT given by the investigator. Outcome measures were the Self-Efficacy for Exercise Scale (SEES) and Self-Efficacy for Functional Activity Scale (SEFAS), the Outcome Expectations for Exercise Scale (OEES) and Outcome Expectations for Functional Activity Scale (OEFAS), the Physical Performance Test (PPT), and the Physical Activity Diary (PAD). RESULTS: The experimental group had significantly greater improvements in self-efficacy for exercise, outcome expectations for exercise, and functional activity, significantly more participation in exercise and walking, and significantly greater improvement in physical performance than did the control group at postoperative weeks 2 and 6. DISCUSSION: The BCI based on SCT was effective in changing the outcomes in the expected direction. This BCI may be applicable, with modifications, to elders in other situations in which changing behavior is the key to recovery.

Aged↗