Biomedical subjects

R A Floyd

Publications and source records attributed to R A Floyd.

At least 37 records · Page 2Linked to original sources

PubMed2000

Nitrone inhibition of age-associated oxidative damage.

The mechanistic basis of the neuroprotective activity of the nitrone-based free radical trap PBN (alpha-phenyl-N-tert-butyl nitrone) has been investigated extensively. Key observations exclude its simple mass action spin trapping of free radicals activity as the key mechanism of action. These include: A) the fact that it protects in experimental stroke even if administered several hours after the event and B) the fact that its chronic low-level administration to old experimental animals reverses their age-enhanced susceptibility to stroke even several days after the last dosage. PBN was found to inhibit gene induction in several models including stroke and an LPS-mediated septic shock model. Stoke causes inducible nitric oxide synthase (iNOS) to be expressed. High levels of nitric oxide and peroxynitrite (formed from nitric oxide), produced by iNOS, is particularly neurotoxic. PBN inhibits iNOS induction. Therefore, it seems that prevention of the formation of neurotoxic products is a rational mechanism of action of PBN in the stroke model. There is strong rationale to consider that there is an enhanced propensity for a "smoldering" neuro-inflammatory state in the old brain. Reversal of this state by PBN may explain its action in preventing age-enhanced stroke susceptibility in old experimental animals. Significant new findings underscore the importance of neuro-inflammatory processes in neuronal death or dysfunction in Alzheimer's disease. Neuro-inflammatory processes implicate enhanced signal transduction processes. Strong evidence for this is the enhanced p38 kinase activation in neurons near plaques and tangles of the Alzheimer's brain in contrast to normal aged-matched control brain which did not show p38 activation. In rat primary astrocytes p38 activation by the pro-inflammatory cytokine IL-1 beta, as well as by H2O2, was significantly suppressed by PBN. Mechanistically it was shown that PBN suppresses the amount of reactive oxygen species (ROS) produced in mitochondrial respiration. Much evidence indicates that ROS are signaling molecules and that they also are involved to maintaining brain phosphatases in an inactive state. We argue that finding a specific high affinity site mechanism for the neuroprotective action of PBN is unlikely based on the complexity of the system reflecting ROS generation and signal transduction processes that have apparently evolved to maintain adaptive responses. The promising pharmacological activity of molecules like PBN is not diminished by this however, for only excessive amounts of ROS is considered detrimental. The action of PBN in suppressing signal transduction processes, most likely by suppressing ROS production in mitochondrial respiration, effectively controls excessive oxidative damage and prevents induction of genes that form neurotoxic products.

Aging↗

PubMed1999

Protection of methamphetamine nigrostriatal toxicity by dietary selenium.

Multiple dose administration of methamphetamine (MA) results in long-lasting toxic effects in the nigrostriatal dopaminergic system. These effects are considered to be primarily due to oxidative damage mediated by increased production of hydrogen peroxide or other reactive oxygen species in the dopaminergic system. The present study was designed to determine the protective effects of dietary antioxidant selenium on MA-induced neurotoxicity in the nigrostriatal dopaminergic system. Male C57BL/6J mice were fed either selenium-deficient (< 0.01 ppm Se) or selenium-replete (0.2 ppm Se) diets for 90 days. MA treatment decreased the dopamine (DA) levels in the striatum and substantia nigra (SN) of both Se-replete and Se-deficient animals. However, in Se-replete animals, this DA depletion was significantly attenuated in both the striatum and SN. A novel observation is that MA administration resulted in increased activity of Cu,Zn-SOD in the brains of both Se-deficient and Se-replete animals. However, MA administration to Se-deficient animals exhibited a higher Cu,Zn-SOD activity in the nigrostriatal system than the control animals. Elevated malondialdehyde (MDA) levels in the striatum and SN were also observed in Se-deficient MA-treated animals. Se repletion significantly increased the glutathione peroxidase (GPx) activity and the ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) in the MA-treated animals. In conclusion, we have shown that dietary Se attenuated methamphetamine neurotoxicity and that this protection involves GPx-mediated antioxidant mechanisms. Even though Cu,Zn-SOD activity was significantly elevated by MA treatment, the role of this enzyme in MA-mediated neurotoxicity is not yet clear.

Animals↗

PubMed1999

Basal protein phosphorylation is decreased and phosphatase activity increased by an antioxidant and a free radical trap in primary rat glia.

Reversible protein phosphorylation regulates a wide array of cellular functions. Cells respond to cytokines and various stressors via phosphorylation and thus activation of one or more of the mitogen-activated protein kinase (MAPK) pathways. Involvement of these signal transduction pathways has been implicated in numerous pathologies, including inflammation. Using a primary glia cell culture, we show here that the antioxidant N-acetylcysteine (NAC) and the nitrone-based free radical trap, alpha-phenyl-N-tert-butyl nitrone (PBN), reduce total basal protein phosphorylation in a concentration-dependent manner as assessed by phosphotyrosine analysis and by [gamma-32P]ATP transfer radioassay. In addition we show that NAC inhibits H2O2-induced phosphatase inactivation in glia cell lysate. The PBN- and NAC-induced reduction in protein phosphorylation is accompanied by an increase in phosphatase activity, suggesting that PBN and NAC reduce protein phosphorylation by globally augmenting oxidant-sensitive phosphatase activities. These results partly explain why certain antioxidants also possess anti-inflammatory actions.

Acetylcysteine↗

PubMed1999

Phenyl-N-tert-butylnitrone demonstrates broad-spectrum inhibition of apoptosis-associated gene expression in endotoxin-treated rats.

Systemic exposure to gram-negative bacterial substances such as lipopolysaccharide (LPS, or endotoxin) induces an uncontrolled, massive inflammatory reaction which culminates in multiple system organ failure and death. Septic shock often does not respond to corticosteroids; however, certain low-molecular-weight antioxidant compounds have been discovered to possess potent anti-inflammatory action, and some of these novel compounds can rescue animals from experimentally induced septic shock. Phenyl-N-tert-butylnitrone (PBN) is the archetype of the nitrone class of antioxidants which we have previously shown to suppress LPS-induced cytokine biosynthesis in vivo. Using a multiprobe ribonuclease protection assay, we now demonstrate the ability of PBN to suppress proapoptotic gene expression in the LPS-induced model of endotoxic shock. The broad-spectrum gene-suppressive affects of PBN are discussed in the context of inflammatory signal transduction and models are proposed to explain why certain antioxidants may also possess anti-inflammatory and antiapoptotic properties.

Animals↗

PubMed1999

Redox-sensitive protein phosphatase activity regulates the phosphorylation state of p38 protein kinase in primary astrocyte culture.

Reactive oxygen species (ROS) have been implicated as second messengers that activate protein kinase cascades, although the means by which ROS regulate signal transduction remains unclear. In the present study, we show that interleukin 1beta (IL1beta), H2O2, and sorbitol-induced hyperosmolarity mediate a 5- to 10-fold increase in phosphorylation (activation) of the p38 protein kinase in rat primary glial cells as measured by analyses of Western blots using an antibody directed against the dually phosphorylated (active) p38. Additionally, IL1beta was found to elicit H2O2 synthesis in these cells. Concurrent with p38 phosphorylation, all three stimulation paradigms caused an inhibition of protein phosphatase activity. Phenyl-tert-butyl nitrone (PBN), a nitrone-based free radical trap and N-acetyl-cysteine (NAC), a thiol reducing agent, were examined for their effects on the phosphorylation of p38 as well as phosphatase activity. Pretreatment of cells with either PBN or NAC at 1.0 mM suppressed IL1beta H2O2, and sorbitol-mediated activation of p38 and significantly increased phosphatase activity. These data suggest that ROS, particularly H2O2, are used as second messenger substances that activate p38 in part via the transient inactivation of regulatory protein phosphatases.

Acetylcysteine↗

PubMed1999

Increased oxidative stress brought on by pro-inflammatory cytokines in neurodegenerative processes and the protective role of nitrone-based free radical traps.

Nitrone-based free radical traps (NFTs) have been shown to be protective in several neurodegenerative models. Our research has strongly implicated that: A) several neurodegenerative conditions exhibit increased levels of pro-inflammatory cytokines which consequently result in increased levels of oxidative stress and B) that NFTs act in part by suppressing oxidative stress through suppression of the action of the cytokine cascade. Acquired Immune Deficiency Syndrome (AIDS) dementia complex (ADC) is one of several conditions where the data collected helped to develop these concepts. Novel observations include demonstration that IL-1beta acts on cultured brain glia cells to invoke protein nitration and oxidative stress and that low levels of PBN (alpha-phenyl tert-butyl nitrone) inhibit this effect. We interpret these data as indicating that PBN prevents IL-1beta mediated peroxynitrite formation. Additionally, we have found that the AIDS viral envelope protein gp120 upregulates mRNA for the cytokines TNF alpha and TNF beta in rat neonatal brain, and that PBN prevents this. Western blots of protein extracts showed upregulation of inducible nitric oxide synthase (iNOS) in gp120 treated neonatal rat brains, and that PBN prevented induction of this enzyme as well. These observations underscore the general concept that PBN inhibits the induction of genes which produce neurotoxic products, one of which is peroxynitrite formed by the reaction of nitric oxide with superoxide, and may act also by inhibiting the induction of cytokines which mediate pro-inflammatory conditions in the brain.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Neuroinflammatory processes are important in neurodegenerative diseases: an hypothesis to explain the increased formation of reactive oxygen and nitrogen species as major factors involved in neurodegenerative disease development.

The hypothesis, as stated in the title, has arisen from the failure of simpler notions to explain a series of otherwise difficult to understand observations and the mounting evidence, in a broader sense, that inflammatory processes in the CNS are important etiologically in neurodegenerative diseases. Novel aspects include the primacy of inflammatory processes, within the CNS, which leads to increased formation of "proinflammatory" cytokines that lead to increased formation of reactive oxygen species (ROS) and mediation of the upregulation of genes that produce toxic products such as reactive nitrogen species (RNS). Here I utilize important background reports and synthesize ideas to help account for the noted increases in ROS and RNS and their biological reaction products in neurodegenerative diseases. The uniqueness of the CNS inflammatory processes include minimal damping of amplification processes, such as proinflammatory cytokine-mediated cascades, combined with unique genetic defects, that act in combination with other risk factors to repeatedly "spark" the inflammatory cascades to account for some of the major differences in neurodegenerative diseases. This hypothesis can be experimentally examined by development of definitive methods to quantitate unique products that are formed by processes predicted to occur under neurodegenerative conditions.

Alzheimer Disease↗

PubMed1999

Production of hydroxyl free radical by brain tissues in hyperglycemic rats subjected to transient forebrain ischemia.

Preischemic hyperglycemia is known to aggravate brain damage resulting from transient ischemia. In the present study, we explored whether this aggravation is preceded by an enhanced formation of reactive oxygen species (ROS) during the early reperfusion period. To that end, normo- and hyperglycemic rats were subjected to 15 min of forebrain ischemia and allowed recovery periods of 5, 15, and 60 min. Sodium salicylate was injected intraperitoneally in a dose of 100 mg/kg, and tissues were sampled during recirculation to allow analyses of salicylic acid (SA) and its hydroxylation products, 2,3- and 2,5-dihydroxybenzoate (DHBA). Tissue sampled from thalamus and caudoputamen in normoglycemic animals failed to show an increase in 2,3- or 2,5-DHBA after 5 and 15 min of recirculation. However, such an increase was observed in the neocortex after 60 min of recirculation, with a suggested increase in the hippocampus as well. Hyperglycemia had three effects. First, it increased 2,5-DHBA in the thalamus and caudoputamen to values exceeding normoglycemic ones after 15 min of recirculation. Second, it increased basal values of 2,5- and total DHBA in the neocortex. Third, it increased the 60-min values for 2,5- and total DHBA in the hippocampus. These results hint that, at least in part, hyperglycemia may aggravate damage by enhancing basal- and ischemia-triggered production of ROS.

Animals↗

PubMed1999

Oxidative DNA damage in circulating leukocytes occurs as an early event in chronic HCV infection.

UNLABELLED: Chronic hepatitis C virus (HCV) infection is associated with an increased production of reactive oxygen species within the liver that are responsible for the oxidation of intracellular macromolecules. To ascertain whether the increased risk of hepatocellular carcinoma in individuals with chronic HCV infection is related to an accumulation of oxidative DNA damage, the 8-hydroxydeoxyguanosine (8-OHdG) content in the DNA of liver tissue and leukocytes of 87 individuals with HCV- or HBV-related liver disease and of 10 healthy controls was measured. Serum levels of thiobarbituric acid reactive substances (TBARS) were also assessed as an index of lipid peroxidation. RESULTS: The 8-OHdG content in the circulating leukocytes correlated with that of liver tissue (r = 0.618, p < .0004). HCV patients had the highest median 8-OHdG levels (p < .0004). 8-OHdG leukocyte levels in HCV patients were higher than in HBV patients (p < .04) and they significantly correlated with the clinical diagnosis (p < .025), the serum ferritin levels (p < .05), and the amount of liver steatosis (p < .001). No correlation was found with age, gender, history of drinking or smoking, ALT or GGT levels, ESR, alpha-1, or gamma-globulin level and Ishak score. TBARS levels were significantly higher in cirrhotics than in noncirrhotics (p < .01). CONCLUSIONS: The 8-OHdG level in circulating leukocytes is a reliable marker of oxidative stress occurring in the liver of individuals with chronic HCV infection. DNA oxidative damage appears to be an early and unique event in the natural history of HCV-related hepatitis. This injury increases the risk of genomic damage and may be one of the important factors involved in the carcinogenic process in cases of HCV-related chronic liver disease.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1999

p38 kinase is activated in the Alzheimer's disease brain.

The p38 mitogen-activated protein kinase is a stress-activated enzyme responsible for transducing inflammatory signals and initiating apoptosis. In the Alzheimer's disease (AD) brain, increased levels of phosphorylated (active) p38 were detected relative to age-matched normal brain. Intense phospho-p38 immunoreactivity was associated with neuritic plaques, neuropil threads, and neurofibrillary tangle-bearing neurons. The antibody against phosphorylated p38 recognized many of the same structures as an antibody against aberrantly phosphorylated, paired helical filament (PHF) tau, although PHF-positive tau did not cross-react with the phospho-p38 antibody. These findings suggest a neuroinflammatory mechanism in the AD brain, in which aberrant protein phosphorylation affects signal transduction elements, including the p38 kinase cascade, as well as cytoskeletal components.

Aged↗

PubMed1999

Antioxidants, oxidative stress, and degenerative neurological disorders.

Recently, clinical trials of several neurodegenerative diseases have increasingly targeted the evaluation of the effectiveness of various antioxidants. The results so far are encouraging but variable and thus confusing. Rationale for the possible clinical effectiveness of antioxidants in several degenerative conditions has arisen out of the many years of basic science generally showing that reactive oxygen species (ROS) and oxidative damage are important factors in the processes involved. Aging is one of the most significant risk factors for degenerative neurological disorders. Basic science efforts in our laboratory have centered on exploring the role of ROS and oxidative stress in neurodegenerative processes. The present review brings together some of the basic concepts we have learned by following this approach for the last 20 years and specifically the results we have obtained by following up on our serendipitous findings that a nitrone-based free radical trap, alpha-phenyl-tert-butylnitrone (PBN), has neuroprotective activity in several experimental neurodegenerative models. The mechanistic basis of the neuroprotective activity of PBN does not appear to rely on its general free radical trapping or antioxidant activity per se, but its activity in mediating the suppression of genes induced by pro-inflammatory cytokines and other mediators associated with enhanced neuroinflammatory processes. Neuroinflammatory processes, induced in part by pro-inflammatory cytokines, yield enhanced ROS and reactive nitric oxide species (RNS) as well as other unknown components that have neurotoxic properties. Neurotoxic amounts of RNS are formed by the activity of inducible nitric oxide synthase (iNOS). The demonstration of enhanced 3-nitro-tyrosine formation in affected regions of the Alzheimer's brain, in comparison to age-matched controls, reinforces the importance of neuroinflammatory processes. iNOS induction involves activation by phosphorylation of the MAP kinase p38 and can be induced in cultured astrocytes by IL-1beta or H2O2. The action of PBN and N-acetyl cysteine to suppress the activation of p38 was demonstrated in cultured astrocytes. The demonstration of activated p38 in neurons surrounding amyloid plaques in affected regions of the Alzheimer's brain attest to enhanced signal transduction processes in this neurodegenerative condition. The major themes of ROS and RNS formation associated with neuroinflammation processes and the suppression of these processes by antioxidants and PBN continue to yield promising leads for new therapies. Outcomes of clinical trials on antioxidants will become less confusing as more knowledge is amassed on the basic processes involved.

Alzheimer Disease↗

PubMed1999

Q beta bacteriophage photoinactivated by methylene blue plus light involves inactivation of its genomic RNA.

Methylene blue (MB) is being used as a sensitizer for the photodynamic inactivation of viral contaminants, including the human immunodeficiency virus, in blood and blood components used in medical treatment. We recently showed that oxygen-dependent photodynamic inactivation of the RNA bacteriophage Q beta with MB plus light (MB + L) is associated with the formation of 8-oxo-7,8-dihydroguanine, protein carbonyls, RNA-protein crosslinkages and minor amounts of RNA strand breaks. We report herein, with the use of infectious RNA assays, that the lethal lesions in Q beta phage following MB + L exposure can be accounted for, and thereby most likely reside in, the RNA component of the phage but that the protein component of the virion contributes to the inactivation. The formation of RNA-protein crosslinkages as the primary inactivating type of lesion is put forth as the most probable model of the inactivation mechanism due to the sensitivity with which RNA-protein crosslinks are formed in response to MB + L exposure and the expectation of the powerful inactivating power of this type of lesion.

Bacteriophages↗

PubMed1998

The presence of two distinct 8-oxoguanine repair enzymes in human cells: their potential complementary roles in preventing mutation.

8-Oxoguanine (8-oxoG), induced by reactive oxygen species (ROS) and ionizing radiation, is arguably the most important mutagenic lesion in DNA. This oxidized base, because of its mispairing with A, induces GC-->TA transversion mutations often observed spontaneously in tumor cells. The human cDNA encoding the repair enzyme 8-oxoG-DNA glycosylase (OGG-1) has recently been cloned, however, its activity was never detected in cells. Here we show that the apparent lack of this activity could be due to the presence of an 8-oxoG-specific DNA binding protein. Moreover, we demonstrate the presence of two antigenically distinct OGG activities with an identical reaction mechanism in human cell (HeLa) extracts. The 38 kDa OGG-1, identical to the cloned enzyme, cleaves 8-oxoG when paired with cytosine, thymine and guanine but not adenine in DNA. In contrast, the newly discovered 36 kDa OGG-2 prefers 8-oxoG paired with G and A. We propose that OGG-1 and OGG-2 have distinct antimutagenic functions in vivo . OGG-1 prevents mutation by removing 8-oxoG formed in DNA in situ and paired with C, while OGG-2 removes 8-oxoG that is incorporated opposite A in DNA from ROS-induced 8-oxodGTP. We predict that OGG-2 specifically removes such 8-oxoG residues only from the nascent strand, possibly by utilizing the same mechanism as the DNA mismatch repair pathway.

Carbon-Oxygen Lyases↗

PubMed1998

Electrochemical analysis of protein nitrotyrosine and dityrosine in the Alzheimer brain indicates region-specific accumulation.

HPLC with electrochemical array detection (HPLC-ECD) was used to quantify 3,3'-dityrosine (diTyr) and 3-nitrotyrosine (3-NO2-Tyr) in four regions of the human brain that are differentially affected in Alzheimer's disease (AD). DiTyr and 3-NO2-Tyr levels were elevated consistently in the hippocampus and neocortical regions of the AD brain and in ventricular cerebrospinal fluid (VF), reaching quantities five- to eightfold greater than mean concentrations in brain and VF of cognitively normal subjects. Uric acid, a proposed peroxynitrite scavenger, was decreased globally in the AD brain and VF. The results suggest that AD pathogenesis may involve the activation of oxidant-producing inflammatory enzyme systems, including nitric oxide synthase.

Aged↗

PubMed1998

Inhibition by phenyl N-tert-butyl nitrone of early phase carcinogenesis in the livers of rats fed a choline-deficient, L-amino acid-defined diet.

Male Wistar rats were fed a choline-deficient, L-amino acid-defined (CDAA) diet alone or in combination with a nitrone-based free radical trapping agent, phenyl N-tert-butyl nitrone (PBN) in the drinking water at the concentrations of 0.013, 0.065, and 0.130% for 12 weeks. PBN inhibited the changes that are normally induced in the livers of rats by the CDAA diet feeding, i.e., development of putative preneoplastic lesions, proliferation of connective tissue, reduction of glutathione S-transferase activity, formation of 8-hydroxyguanine in DNA, and an increase in inducible cyclo-oxygenase (COX2) activity. PBN, however, did not prevent the increases in the COX2 mRNA or protein levels brought on by the CDAA diet These results indicate that the loss of glutathione S-transferase activity and COX2 induction may play significant roles in rat liver carcinogenesis by the CDAA diet and that PBN prevents neoplasia not only by its radical scavenging activity but also by inhibiting COX2 activity at the catalytic level.

Amino Acids↗

PubMed1998

Thiol-dependent metal-catalyzed oxidation of copper, zinc superoxide dismutase.

Superoxide dismutase (SOD) is a key enzyme in the antioxidant system of the cells. When exposed to a metal-catalyzed oxidation (MCO) system composed of Fe3+, O2, and thiol as an electron donor copper, zinc SOD (CuZnSOD) was susceptible to oxidative modification and damage as indicated by the loss of activity, fragmentation and aggregation of peptide as well as by the formation of carbonyl groups. Oxidative damage to CuZnSOD was inhibited by diethylenetriaminepentaacetic acid as well as by free radical scavengers and spin-trapping agents. The results of the present study indicate that hydrogen peroxide may be generated from a thiol/Fe3+/O2 system and that hydroxyl free radicals, produced by metal-catalyzed Fenton reactions, may be the ultimate species mediating the SOD damage. Incubation with the MCO system resulted in the release of Cu ions from CuZnSOD. Incubation with the thiol-MCO did not significantly increase the formation of 2-oxohistidine in CuZnSOD. The lack of formation of 2-oxohistidine, as well as the pronounced preventive effect of spin-traps on the thiol-MCO-mediated damage to CuZnSOD, indicates that inactivation might actually be predominantly due to global oxidation rather than a site-specific oxidation. The thiol-MCO-mediated damage to SOD may result in the perturbation of cellular antioxidant defense mechanisms and subsequently lead to a pro-oxidant condition.

Chelating Agents↗

PubMed1998

Prevention of reoxygenation injury by sodium salicylate in isolated-perfused rat liver.

Sodium salicylate can be used as a chemical trap for hydroxyl radicals, the most damaging reactive oxygen species. Because reactive oxygen species are involved in the pathogenesis of hepatic hypoxia/reoxygenation injury, the goal of this study was to determine if trapping hydroxyl radicals with salicylate would prevent or at least ameliorate such injury. Isolated rat livers, continuously perfused with Krebs-Henseleit bicarbonate buffer in the presence or absence of salicylate (2 mM), were exposed, after 30 min of recovery, to 60 min of hypoxia, followed by 30 min of reoxygenation. During reoxygenation, control livers experienced a sharp increase in the rate of lactic dehydrogenase release, taken as index of cell injury, protein carbonyl content, and malondialdehyde, taken as index of protein oxidation and lipid peroxidation, respectively. The presence of salicylate in the solution perfusion significantly reduced the rate of lactic dehydrogenase release, protein carbonyl content, and malondialdehyde production during reoxygenation. Hepatic histology documented a significantly reduced cell injury in salicylate-perfused livers compared to control livers. These data suggest that the hydroxyl radical chemical trap sodium salicylate, acting as an antioxidant, may represents an effective agent to reduce liver injury due to hypoxia/reoxygenation in a model of isolated-perfused rat liver.

Animals↗

PubMed1998

Effects of short-term sleep deprivation on murine immunity to influenza virus in young adult and senescent mice.

Sleep has been proposed as an innate host defense, exerting effects on both specific and nonspecific immunity. In one of the more striking papers dealing with the effects of sleep on specific immunity, Brown et al (Reg. Immunol. 1989; 2: 321-325) reported that depriving influenza virus-immune mice of sleep for 7 hours following total respiratory tract viral challenge abrogated anti-viral immunity within the lungs and lowered the level of anti-influenza antibody in lung homogenates. In the solidly-immune convalescent mouse, nasobronchial immunity to influenza virus has been shown to be due to secretory IgA (S-IgA) within the mucosal mucocilliary blanket, while serum IgG has been shown to mediate protection within the lung parenchyma. In this study we attempted to duplicate the work of Brown et al in solidly immune mice. We were unable to abrogate mucosal anti-influenza viral immunity with a single post-viral-challenge sleep-deprivation episode, nor were we able to depress this immunity with one pre- and two post-challenge sleep-deprivation episodes in young adult or old mice, or with two pre-challenge sleep-deprivation episodes in old mice. Sleep deprivation did not depress the level of serum influenza-specific IgG antibodies, and resulted in increased influenza-specific serum IgG compared with normally sleeping mice in aged immune mice boosted 3 weeks before challenge and sleep deprived once before and twice after challenge (p = 0.005). No differences in anti-viral respiratory immunity were apparent between young and old mice. We conclude that short-term sleep deprivation has minimal effects on pre-existing mucosal and humoral immunity in either the young adult or the senescent mouse.

Aging↗