Behavioral evidence for geomagnetic imprinting and transgenerational inheritance in fruit flies.

Certain long-distance migratory animals, such as salmon and sea turtles, are thought to imprint on the magnetic field of their natal area and to use this information to help them return as adults. Despite a growing body of indirect support for such imprinting, direct experimental evidence thereof remains elusive. Here, using the fruit fly as a magnetoreceptive model organism, we demonstrate that exposure to a specific geographic magnetic field during a critical period of early development affected responses to a matching magnetic field gradient later in life. Specifically, hungry flies that had imprinted on a specific magnetic field from 1 of 3 widely separated geographic locations responded to the imprinted field, but not other magnetic fields, by moving downward, a geotactic behavior associated with foraging. This same behavior occurred spontaneously in the progeny of the next generation: female progeny moved downward in response to the field on which their parents had imprinted, whereas male progeny did so only in the presence of these females. These results represent experimental evidence that organisms can learn and remember a magnetic field to which they were exposed during a critical period of development. Although the function of the behavior is not known, one possibility is that imprinting on the magnetic field of a natal area assists flies and their offspring in recognizing locations likely to be favorable for foraging and reproduction.

Antioxidant Activity of Hydrogen Water Mask Pack Composed of Gel-Type Emulsion and Hydrogen Generation Powder.

In this study, hydrogen generation powder samples were prepared using zinc carbonate as a precursor, at a temperature varying from 400 to 700 °C in H2 atmosphere, and were characterized in terms of antioxidant activity. The concentration of dissolved hydrogen obtained by the powder samples was measured using a dissolved hydrogen meter as a function of time. In addition, the antioxidant activity of the samples was evaluated based on the Oyaizu's method, removal rate of ·OH radicals, and ferric reducing antioxidant power. Finally, the hydrogen mask pack was fabricated using the hydrogen generation powder sample and gel-type emulsion. In the clinical test on the mask pack, the effect of the mask on skin aging was characterized and compared to that of a commercial sample. The skin densities of the participants in the experimental group and the control group increased by 18.41% and 9.93% after 4 weeks, respectively. The improved skin density of the participants who used the hydrogen mask pack in the experimental group, might be attributed to the recovery effect of the hydrogen molecule in the mask pack on the denatured thick skin layer.

Inhibitory Effects of ß-Caryophyllene on Helicobacter pylori Infection In Vitro and In Vivo.

The human specific bacterial pathogen Helicobacter pylori (H. pylori) is associated with severe gastric diseases, including gastric cancer. Recently, the increasing resistance makes the usage of antibiotics less effectively. Therefore, development of a new antimicrobial agent is required to control H. pylori infection. In the current study, the inhibitory effect of ß-caryophyllene on H. pylori growth, as well as the antibacterial therapeutic effect, has been demonstrated. ß-caryophyllene inhibited H. pylori growth via the downregulation of dnaE, dnaN, holB, and gyrA and also downregulated virulence factors such as CagA, VacA, and SecA proteins. ß-caryophyllene inhibited expression of several T4SS components, so that CagA translocation into H. pylori-infected AGS gastric cancer cells was decreased by ß-caryophyllene treatment. ß-caryophyllene also inhibited VacA entry through the downregulation of T5aSS. After ß-caryophyllene administration on Mongolian gerbils, the immunohistochemistry (IHC) and Hematoxylin&Eosin stains showed therapeutic effects in the treated groups. Hematological data, which was consistent with histological data, support the therapeutic effect of ß-caryophyllene administration. Such a positive effect of ß-caryophyllene on H. pylori infection potently substantiates the natural compound as being capable of being used as a new antimicrobial agent or functional health food to help patients who are suffering from gastroduodenal diseases due to H. pylori infection.

Anti-inflammatory effects of Kaempferol on Helicobacter pylori-induced inflammation.

Inflammation induced by Helicobacter pylori infection related to gastric carcinogenesis. In this study, we have investigated the anti-inflammatory effect and its mechanism of kaempferol in the inflammatory response caused by H. pylori infection in vitro. We found that kaempferol reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-8) and production of IL-8 in AGS cells. In addition, kaempferol suppressed translocation of cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) of H. pylori to AGS cells. It was due to decreased transcription of type IV secretion system (T4SS) components involved in CagA injection and secretion system subunit protein A (SecA) of type V secretion system (T5SS) involved in VacA secretion by kaempferol. In conclusion, kaempferol shows the anti-inflammatory effect by suppressing the translocation of CagA and VacA proteins and leading to the down-regulation of pro-inflammatory cytokines. Abbreviations: CagA: cytotoxin-associated gene A; VacA: vacuolating cytotoxin A; T4SS: type IV secretion systems; SecA: secretion system subunit protein A; T5SS: type V secretion system.

Bleb-associated endophthalmitis: Proportion, presentation, management and outcomes in Victoria, Australia.

IMPORTANCE: Bleb-associated endophthalmitis is a potentially vision-threatening complication of trabeculectomy. With improvements in surgical technique and changing patterns of intraoperative antimetabolite use, a re-evaluation of the incidence of bleb-associated endophthalmitis is warranted. BACKGROUND: To investigate changes in the incidence, presentation, management and outcomes of bleb-associated endophthalmitis between 1997 and 2015 in Victoria, Australia. DESIGN: A retrospective cohort analysis. PARTICIPANTS: Consecutive cases of bleb-associated endophthalmitis managed at the Royal Victorian Eye and Ear Hospital (RVEEH) between 1997 and 2015. METHODS: Medical record review of consecutive cases of bleb-associated endophthalmitis and statistical analysis were performed. MAIN OUTCOME MEASURES: Visual acuity, including loss of light perception, intraocular pressure, and need for further surgery. RESULTS: Sixty-seven eyes with bleb-associated endophthalmitis (BAE) were identified. Of these, 41 had trabeculectomy performed in Victoria during the study period, over which time 11 129 trabeculectomies were performed. The proportion of BAE was stable over time (0.4%). The mean age at presentation was 73.7 ± 12.1 years old and the majority of patients were Caucasian (79.1%). The mean duration between glaucoma filtration surgery and the development of bleb-associated endophthalmitis was 3 years (Interquartile Range = 0.4-6.0 years). The cultures were positive in 71.6% of cases. Approximately 1 in 8 patients required enucleation. The final visual acuity was poor with a Snellen Visual Acuity (VA) of 6/60 or worse in two-thirds of patients. CONCLUSIONS AND RELEVANCE: Bleb-associated endophthalmitis is an uncommon complication following glaucoma filtration surgery. The proportion has remained stable over time. Visual outcomes remain poor.

Inhibitory Effects of Menadione on Helicobacter pylori Growth and Helicobacter pylori-Induced Inflammation via NF-κB Inhibition.

H. pylori is classified as a group I carcinogen by WHO because of its involvement in gastric cancer development. Several reports have suggested anti-bacterial effects of menadione, although the effect of menadione on major virulence factors of H. pylori and H. pylori-induced inflammation is yet to be elucidated. In this study, therefore, we demonstrated that menadione has anti-H. pylori and anti-inflammatory effects. Menadione inhibited growth of H. pylori reference strains and clinical isolates. Menadione reduced expression of vacA in H. pylori, and translocation of VacA protein into AGS (gastric adenocarcinoma cell) was also decreased by menadione treatment. This result was concordant with decreased apoptosis in AGS cells infected with H. pylori. Moreover, cytotoxin-associated protein A (CagA) translocation into H. pylori-infected AGS cells was also decreased by menadione. Menadione inhibited expression of several type IV secretion system (T4SS) components, including virB2, virB7, virB8, and virB10, that are responsible for translocation of CagA into host cells. In particular, menadione inhibited nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) activation and thereby reduced expression of the proinflammatory cytokines such as IL-1ß, IL-6, IL-8, and TNF-α in AGS as well as in THP-1 (monocytic leukemia cell) cell lines. Collectively, these results suggest the anti-bacterial and anti-inflammatory effects of menadione against H. pylori.

DDA3 and Mdp3 modulate Kif2a recruitment onto the mitotic spindle to control minus-end spindle dynamics.

Active turnover of spindle microtubules (MTs) for the formation of a bi-orientated spindle, chromosome congression and proper chromosome segregation is regulated by MT depolymerases such as the kinesin-13 family and the plus-end-tracking proteins (+TIPs). However, the control mechanisms underlying the spindle MT dynamics that are responsible for poleward flux at the minus end of MTs are poorly understood. Here, we show that Mdp3 (also known as MAP7D3) forms a complex with DDA3 (also known as PSRC1) and controls spindle dynamics at the minus end of MTs by inhibiting DDA3-mediated Kif2a recruitment to the spindle. Aberrant Kif2a activity at the minus end of spindle MTs in Mdp3-depleted cells decreased spindle stability and resulted in unaligned chromosomes in metaphase, lagging chromosomes in anaphase, and chromosome bridges in telophase and cytokinesis. Although they play opposing roles in minus-end MT dynamics, acting as an MT destabilizer and an MT stabilizer, respectively, DDA3 and Mdp3 did not affect the localization of each other. Thus, the DDA3 complex orchestrates MT dynamics at the MT minus end by fine-tuning the recruitment of Kif2a to regulate minus-end MT dynamics and poleward MT flux at the mitotic spindle.

Surgical outcomes of trabeculectomy and glaucoma drainage implant for uveitic glaucoma and relationship with uveitis activity.

IMPORTANCE: This study provides ophthalmologists who manage uveitic glaucoma with important information on factors that can affect the success of surgical management of this challenging disease. BACKGROUND: This study examines surgical outcomes of trabeculectomy and glaucoma device implant (GDI) surgery for uveitic glaucoma, in particular the effect of uveitis activity on surgical outcomes. DESIGN: Retrospective chart review at a tertiary institution. SAMPLES: Eighty-two cases with uveitic glaucoma (54 trabeculectomies and 28 (GDI) surgeries) performed between 1 December 2006 and 30 November 2014. METHODS: Associations of factors with surgical outcomes were examined using univariate and multivariate analysis. MAIN OUTCOME MEASURES: Surgical outcomes as defined in Guidelines from World Glaucoma Association. RESULTS: Average follow up was 26.4 ± 21.5 months. Overall qualified success rate of the trabeculectomies was not statistically different from GDI, being 67% and 75%, respectively (P = 0.60). Primary and secondary GDI operations showed similar success rates. The most common postoperative complication was hypotony (~30%). Active uveitis at the time of operation was higher in trabeculectomy compared with GDI group (35% vs. 14%). Active uveitis at the time of surgery did not significantly increase risk of failure for trabeculectomies. Recurrence of uveitis was significantly associated with surgical failure in trabeculectomy group (odds ratio 4.8, P = 0.02) but not in GDI group. CONCLUSIONS AND RELEVANCE: Surgical success rate of GDI was not significantly different from trabeculectomy for uveitic glaucoma in this study. Regular monitoring, early and prolonged intensive treatment of ocular inflammation is important for surgical success particularly following trabeculectomy.

Self-management Experiences of Older Korean Women With Urinary Incontinence: A Descriptive Qualitative Study Using Focus Groups.

PURPOSE: The purpose of this study was to explore the self-management experiences of Korean women with urinary incontinence (UI). DESIGN: Descriptive, qualitative study using focus groups. SUBJECTS AND SETTING: Twenty-two community-dwelling women, 65 years and older, participated in 3 focus-group interviews. Participants were recruited from 2 elderly halls and 1 senior welfare center in South Korea. METHODS: Three focus group interviews comprising 6 to 8 individuals were conducted in a quiet venue at the elderly hall or senior welfare center. Two investigators performed the interviews; one acted as moderator and one as notetaker; interviews began with scripted open-ended questions. All interviews were electronically recorded and transcribed verbatim. Using an inductive thematic approach, data were first analyzed by the first and second authors; and all 4 authors contributed to coding and agreed on final themes. RESULTS: Korean women perceived UI as a loss of dignity, an odor problem, an uncontrollable disease, and a life impairment. Thematic analysis revealed 4 themes regarding the self-management experience of UI: preserving self-respect in the sociocultural environment, deodorizing the smell, keeping the secret of uncontrollability, and adjusting to an impaired life. CONCLUSIONS: Women in this study used various daily-living strategies to manage UI, but they mainly implemented strategies to keep UI a secret, including restrictions in activities of daily living. Educational approaches are needed to inform women with UI about more effective management skills.

Ska1 cooperates with DDA3 for spindle dynamics and spindle attachment to kinetochore.

Spindle microtubules (MTs) capture kinetochores (KTs) on the centromere sequence of sister chromatids to align at the mitotic equator and segregate toward spindle poles during mitosis. For efficient chromosome capture, KTs initially attach to the lateral surface of a MT, providing a considerably larger contact surface than the MT tip. A sequential change of KT composition upon spindle attachment enables a conversion from lateral to stable end-on attachment. However, the molecular link between spindle dynamics and KT composition is not fully understood. Here, we report that Ska1 and DDA3 act as molecular linkers in the interplay between KTs and spindle dynamics. After recruitment of Kif2a onto the mitotic spindle by DDA3, Ska1 targets Kif2a to the minus-end of spindle MTs and facilitates spindle dynamics. Furthermore, DDA3 targets Ska1 to KTs to stabilize end-on attachment. Thus, our findings identified a definite regulatory mechanism of the search and capture process for stable spindle attachment through cross-talk between spindle dynamics and KT composition mediated by DDA3 and Ska1.

Lived experience of Korean nurses caring for patients on maintenance haemodialysis.

AIMS AND OBJECTIVES: To understand the lived experience of nurses who care for people undergoing maintenance haemodialysis. BACKGROUND: There is a lack of research regarding the lived experience of nurses caring for people undergoing chronic haemodialysis, in spite of an increased number of nurses and patients. DESIGN: A qualitative descriptive phenomenological study was conducted. METHODS: Fourteen nurses working at two haemodialysis centres in Korea were selected via purposive sampling and participated in in-depth interviews. Data were collected from October 2013-January 2014 and analysed using the phenomenological research method. RESULTS: Four themes were extracted for haemodialysis nurses' caring experience: feelings of pity for clients scheduled for haemodialysis treatment; continuous effort to establish good relationships with clients; feeling comfortable with clients, as though they were family or friends; and reflecting on their own lives through the lives of clients. CONCLUSIONS: Haemodialysis nurses experienced therapeutic relationships while taking care of clients undergoing haemodialysis; they also experienced maturation through reflection on their lives as nurses and human beings. An understanding of nurses' experiences in caring for people undergoing haemodialysis should be the basis of practice, education and nursing research in haemodialysis. RELEVANCE TO CLINICAL PRACTICE: This study could be helpful in enabling nursing students and/or nurses to understand the experience of caring and its meaning with respect to clients undergoing haemodialysis.

Tussilagone suppresses colon cancer cell proliferation by promoting the degradation of ß-catenin.

Abnormal activation of the Wnt/ß-catenin signaling pathway frequently induces colon cancer progression. In the present study, we identified tussilagone (TSL), a compound isolated from the flower buds of Tussilago farfara, as an inhibitor on ß-catenin dependent Wnt pathway. TSL suppressed ß-catenin/T-cell factor transcriptional activity and down-regulated ß-catenin level both in cytoplasm and nuclei of HEK293 reporter cells when they were stimulated by Wnt3a or activated by an inhibitor of glycogen synthase kinase-3ß. Since the mRNA level was not changed by TSL, proteasomal degradation might be responsible for the decreased level of ß-catenin. In SW480 and HCT116 colon cancer cell lines, TSL suppressed the ß-catenin activity and also decreased the expression of cyclin D1 and c-myc, representative target genes of the Wnt/ß-catenin signaling pathway, and consequently inhibited the proliferation of colon cancer cells. Taken together, TSL might be a potential chemotherapeutic agent for the prevention and treatment of human colon cancer.

Driving-Related Glucose Patterns Among Older Adults with Type 1 Diabetes.

Older adults with type 1 diabetes may face challenges driving safely. Glucose "above-5-to-drive" is often recommended for insulin-treated diabetes to minimize hypoglycemia while driving. However, the effectiveness of this recommendation among older adults has not been evaluated. Older drivers with type 1 diabetes were assessed while using sensor-augmented insulin pumps during a 2-week clinical trial run-in. Twenty-three drivers (median age 69 years [interquartile range; IQR 65-72]; diabetes duration 37 years [20-45]) undertook 618 trips (duration 10 min [5-21]). Most trips (n = 535; 87%) were <30 min duration; 9 trips (1.5%) exceeded 90 min and 3 trips (0.5%) exceeded 120 min. Pre-trip continuous glucose monitoring (CGM) was >5.0 mmol/L for 577 trips (93%) and none of these had CGM <3.9 mmol/L during driving (including 8 trips >90 min and 3 trips >120 min). During 41 trips with pre-trip CGM ≤5.0 mmol/L, 11 trips had CGM <3.9 mmol/L. Seventy-one CGM alerts occurred during 60 trips (10%), of which 54 of 71 alerts (76%) were unrelated to hypoglycemia. Our findings support a glucose "above-5-to-drive" recommendation to avoid CGM-detected hypoglycemia among older drivers, including for prolonged drives, and highlight the importance of active CGM low-glucose alerts to prevent hypoglycemia during driving. Driving-related CGM usability and alert functionality warrant investigation. Clinical trial ACTRN1261900515190.

Microstructures and electrochemical properties of Si-Ni-xTi alloys for anode materials.

The phase change due to varying content of titanium in Si-Ni-xTi alloys and its effect on the electrochemical behavior has been investigated. Specimens were prepared by melt-spinning to reduce the microstructure scale. Results showed that silicon particles of 50-100 nm diameter and dendrites of somewhat larger scale were formed in the Si-Ni-Ti alloys ribbons. The microstructure of Si70Ni15Ti15 alloy ribbons was composed of silicon particles finely dispersed in Si7Ni4Ti4 phase. The cycle performance was improved by the formation of TiSi2 or NiSi2 phase at the presence of Si7Ni4Ti4 phase, either of which combined with Si7Ni4Ti4 phase effectively accommodated the volume change of silicon particles during cycling. The reduced scale of silicon particles contributed to the enhanced cycle efficiency as well.

Microstructures and electrochemical properties of Si-xTiNi alloys for lithium secondary batteries.

The rapidly solidified Si-xTiNi (x = 0.2-0.45) alloy ribbons were fabricated via melt spinning process. The thickness of the melt-spun ribbons was about 12.5 microm, and the sound section was selected for the experiment. The microstructures of the ribbons were analyzed using XRD, FE-SEM, and HR-TEM: The primary silicon particles of 30 nm-100 n min diameter were finely dispersed in the inactive buffering matrix of Si7Ni4Ti4 phase. The charge/discharge energy capacity and electrochemical properties were significantly influenced by the relative ratio of NiTi to silicon. With increasing the total amount of Ni and Ti content up to 45 at%, the amount of Si7Ni4Ti4 phase increased and the cycle performance was improved. The Si7Ni4Ti4 phase acted as a buffer for the volume expansion/contraction of Si occurring during the alloying and dealloying, and it could prevent a significant deterioration in cycle performance of the battery.

Human magnetic sense is mediated by a light and magnetic field resonance-dependent mechanism.

Numerous organisms use the Earth's magnetic field as a sensory cue for migration, body alignment, or food search. Despite some contradictory reports, yet it is generally accepted that humans do not sense the geomagnetic field. Here, we demonstrate that a magnetic field resonance mechanism mediates light-dependent magnetic orientation in men, using a rotary chair experiment combined with a two-alternative forced choice paradigm. Two groups of subjects were classified with different magnetic orientation tendencies depending on the food context. Magnetic orientation of the subjects was sensitive to the wavelength of incident light and was critically dependent on blue light reaching the eyes. Importantly, it appears that a magnetic field resonance-dependent mechanism mediates these responses, as evidenced by disruption or augmentation of the ability to orient by radiofrequency magnetic fields at the Larmor frequency and the dependence of these effects on the angle between the radiofrequency and geomagnetic fields. Furthermore, inversion of the vertical component of the geomagnetic field revealed a non-canonical inclination compass effect on the magnetic orientation. These results establish the existence of a human magnetic sense and suggest an underlying quantum mechanical magnetoreception mechanism.

Behavioral Engagement With Playable Objects Resolves Stress-Induced Adaptive Changes by Reshaping the Reward System.

BACKGROUND: The reward system regulates motivated behavior, and repeated practice of specific motivated behavior might conversely modify the reward system. However, the detailed mechanisms by which they reciprocally regulate each other are not clearly understood. METHODS: Mice subjected to chronic restraint stress show long-lasting depressive-like behavior, which is rescued by continual engagement with playable objects. A series of molecular, pharmacological, genetic, and behavioral analyses, combined with microarray, liquid chromatography, and chemogenetic tools, are used to investigate the neural mechanisms of antidepressive effects of playable objects. RESULTS: Here, we show that repeated restraint induces dopamine surges into the nucleus accumbens-lateral shell (NAc-lSh), which cause upregulation of the neuropeptide PACAP in the NAc-lSh. As repeated stress is continued, the dopamine surge by stressors is adaptively suppressed without restoring PACAP upregulation, and the resulting enhanced PACAP inputs from NAc-lSh neurons to the ventral pallidum facilitate depressive-like behaviors. Continual engagement with playable objects in mice subjected to chronic stress remediates reduced dopamine response to new stressors, enhanced PACAP upregulation, and depressive-like behaviors. Overactivation of dopamine D1 receptors over the action of D2 receptors in the NAc-lSh promotes depressive-like behaviors. Conversely, inhibition of D1 receptors or PACAP upregulation in the NAc-lSh confers resilience to chronic stress-induced depressive-like behaviors. Histochemical and chemogenetic analyses reveal that engagement with playable objects produces antidepressive effects by reshaping the ventral tegmental area-to-NAc-lSh and NAc-lSh-to-ventral pallidum circuits. CONCLUSIONS: These results suggest that behavioral engagement with playable objects remediates depressive-like behaviors by resolving stress-induced maladaptive changes in the reward system.

Hyperoxygenation Ameliorates Stress-induced Neuronal and Behavioral Deficits.

Hyperoxygenation therapy remediates neuronal injury and improves cognitive function in various animal models. In the present study, the optimal conditions for hyperoxygenation treatment of stress-induced maladaptive changes were investigated. Mice exposed to chronic restraint stress (CRST) produce persistent adaptive changes in genomic responses and exhibit depressive-like behaviors. Hyperoxygenation treatment with 100% O2 (HO2) at 2.0 atmospheres absolute (ATA) for 1 h daily for 14 days in CRST mice produces an antidepressive effect similar to that of the antidepressant imipramine. In contrast, HO2 treatment at 2.0 ATA for 1 h daily for shorter duration (3, 5, or 7 days), HO2 treatment at 1.5 ATA for 1 h daily for 14 days, or hyperbaric air treatment at 2.0 ATA (42% O2) for 1 h daily for 14 days is ineffective or less effective, indicating that repeated sufficient hyperoxygenation conditions are required to reverse stress-induced maladaptive changes. HO2 treatment at 2.0 ATA for 14 days restores stress-induced reductions in levels of mitochondrial copy number, stress-induced attenuation of synaptophysin-stained density of axon terminals and MAP-2-staining dendritic processes of pyramidal neurons in the hippocampus, and stress-induced reduced hippocampal neurogenesis. These results suggest that HO2 treatment at 2.0 ATA for 14 days is effective to ameliorate stress-induced neuronal and behavioral deficits.

Repeated exposure with short-term behavioral stress resolves pre-existing stress-induced depressive-like behavior in mice.

Chronic stress induces adaptive changes in the brain via the cumulative action of glucocorticoids, which is associated with mood disorders. Here we show that repeated daily five-minute restraint resolves pre-existing stress-induced depressive-like behavior in mice. Repeated injection of glucocorticoids in low doses mimics the anti-depressive effects of short-term stress. Repeated exposure to short-term stress and injection of glucocorticoids activate neurons in largely overlapping regions of the brain, as shown by c-Fos staining, and reverse distinct stress-induced gene expression profiles. Chemogenetic inhibition of neurons in the prelimbic cortex projecting to the nucleus accumbens, basolateral amygdala, or bed nucleus of the stria terminalis results in anti-depressive effects similarly to short-term stress exposure, while only inhibition of neurons in the prelimbic cortex projecting to the bed nucleus of the stria terminalis rescues defective glucocorticoid release. In summary, we show that short-term stress can reverse adaptively altered stress gains and resolve stress-induced depressive-like behavior.

Aging increases vulnerability to stress-induced depression via upregulation of NADPH oxidase in mice.

Brain aging proceeds with cellular and molecular changes in the limbic system. Aging-dependent changes might affect emotion and stress coping, yet the underlying mechanisms remain unclear. Here, we show aged (18-month-old) mice exhibit upregulation of NADPH oxidase and oxidative stress in the hippocampus, which mirrors the changes in young (2-month-old) mice subjected to chronic stress. Aged mice that lack p47phox, a key subunit of NADPH oxidase, do not show increased oxidative stress. Aged mice exhibit depression-like behavior following weak stress that does not produce depressive behavior in young mice. Aged mice have reduced expression of the epigenetic factor SUV39H1 and its upstream regulator p-AMPK, and increased expression of Ppp2ca in the hippocampus-changes that occur in young mice exposed to chronic stress. SUV39H1 mediates stress- and aging-induced sustained upregulation of p47phox and oxidative stress. These results suggest that aging increases susceptibility to stress by upregulating NADPH oxidase in the hippocampus.