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  1. Article: The multifactorial impact of receiving a hereditary angioedema diagnosis.

    Raasch, Jason / Glaum, Mark C / O'Connor, Maeve

    The World Allergy Organization journal

    2023  Volume 16, Issue 6, Page(s) 100792

    Abstract: Hereditary angioedema (HAE) is a rare, chronic, debilitating genetic disorder characterized by recurrent, unpredictable, and potentially life-threatening episodes of swelling that typically affect the extremities, face, abdomen, genitals, and larynx. The ...

    Abstract Hereditary angioedema (HAE) is a rare, chronic, debilitating genetic disorder characterized by recurrent, unpredictable, and potentially life-threatening episodes of swelling that typically affect the extremities, face, abdomen, genitals, and larynx. The most frequent cause of HAE is a mutation in the
    Language English
    Publishing date 2023-06-30
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2581968-9
    ISSN 1939-4551
    ISSN 1939-4551
    DOI 10.1016/j.waojou.2023.100792
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Brain-derived neurotrophic factor and inflammation in depression: Pathogenic partners in crime?

    Porter, Grace A / O'Connor, Jason C

    World journal of psychiatry

    2022  Volume 12, Issue 1, Page(s) 77–97

    Abstract: Major depressive disorder is a debilitating disorder affecting millions of people each year. Brain-derived neurotrophic factor (BDNF) and inflammation are two prominent biologic risk factors in the pathogenesis of depression that have received ... ...

    Abstract Major depressive disorder is a debilitating disorder affecting millions of people each year. Brain-derived neurotrophic factor (BDNF) and inflammation are two prominent biologic risk factors in the pathogenesis of depression that have received considerable attention. Many clinical and animal studies have highlighted associations between low levels of BDNF or high levels of inflammatory markers and the development of behavioral symptoms of depression. However, less is known about potential interaction between BDNF and inflammation, particularly within the central nervous system. Emerging evidence suggests that there is bidirectional regulation between these factors with important implications for the development of depressive symptoms and anti-depressant response. Elevated levels of inflammatory mediators have been shown to reduce expression of BDNF, and BDNF may play an important negative regulatory role on inflammation within the brain. Understanding this interaction more fully within the context of neuropsychiatric disease is important for both developing a fuller understanding of biological pathogenesis of depression and for identifying novel therapeutic opportunities. Here we review these two prominent risk factors for depression with a particular focus on pathogenic implications of their interaction.
    Language English
    Publishing date 2022-01-19
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2220-3206
    ISSN 2220-3206
    DOI 10.5498/wjp.v12.i1.77
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: The Influence of Branched-Chain Amino Acid Supplementation on Fatigue and Tryptophan Metabolism After Acute and Chronic Exercise in Older Adults: Protocol for a Pilot Randomized Controlled Trial.

    Robbins, Ronna N / Cortes, Tiffany / O'Connor, Jason C / Jiwani, Rozmin / Serra, Monica C

    JMIR research protocols

    2023  Volume 12, Page(s) e52199

    Abstract: Background: Fatigue is a strong predictor of negative health outcomes in older adults. Kynurenine, a metabolite of tryptophan, is strongly associated with fatigue. Reductions in fatigue are observed with exercise; however, exercise training does not ... ...

    Abstract Background: Fatigue is a strong predictor of negative health outcomes in older adults. Kynurenine, a metabolite of tryptophan, is strongly associated with fatigue. Reductions in fatigue are observed with exercise; however, exercise training does not completely alleviate symptoms. Branched-chain amino acids (BCAAs) have been shown to have advantageous effects on exercise performance and compete with kynurenine for transport into the central nervous system. Thus, the combination of BCAA and exercise may exert synergized effects of mental and physical fatigue. Therefore, we hypothesize that BCAA added to exercise will shift kynurenine metabolism toward enhanced synthesis of kynurenic acid, thereby reducing fatigue.
    Objective: This randomized, double-blind, placebo-controlled trial aims to compare the effects of acute (approximately 45 min) and chronic (8 wk) exercise with and without BCAA supplementation on mental and physical fatigue and assess whether the hypothesized outcomes are modulated by changes in kynurenine metabolism in 30 older adults (n=15, 50% per group).
    Methods: Older adults (aged 60-80 y) who do not exercise >2 days per week and self-report fatigue (≥3 on a scale of 1-10) will be recruited. Participants will be randomized to either the exercise+BCAA group or exercise+placebo group. Participants will engage in high-volume, moderate-intensity, whole-body exercise training (aerobic and resistance exercise; either in-person or web-based sessions) 3 times per week for 8 weeks. In addition, participants will consume daily either 100 mg/kg body weight of BCAA (2:1:1 leucine:isoleucine:valine) or placebo (maltodextrin) throughout the 8-week intervention. BCAA and placebo powders will be identical in color and dissolved in 400 mL of water and 2.5 g of a calorie-free water flavor enhancer. Muscle biopsies will be collected before and after the intervention after a 12-hour fast to examine changes in the biomarkers of tryptophan metabolism and inflammation. Our primary outcomes include changes in mental and physical fatigue and metabolism after the 8-week exercise training between the 2 groups. Mental and physical fatigue will be measured before and after the intervention. Mental fatigue will be subjectively assessed through the completion of validated questionnaires. Physical fatigue will be measured by isometric handgrip, 1-repetition maximum, chair rise, 400-meter walk, and cardiopulmonary exercise tests.
    Results: The study was funded in March 2022, with an anticipated projected data collection period lasting from January 2023 through December 2023.
    Conclusions: The discovery that kynurenine concentrations are associated with fatigue and are responsive to BCAA supplementation during exercise training could have important implications for the development of future interventions, both lifestyle and pharmacologic, to treat fatigue in older adults.
    Trial registration: ClinicalTrials.gov NCT05484661; https://www.clinicaltrials.gov/study/NCT05484661.
    International registered report identifier (irrid): DERR1-10.2196/52199.
    Language English
    Publishing date 2023-11-01
    Publishing country Canada
    Document type Journal Article
    ZDB-ID 2719222-2
    ISSN 1929-0748
    ISSN 1929-0748
    DOI 10.2196/52199
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Chronic Unpredictable Stress Alters Brain Tryptophan Metabolism and Impairs Working Memory in Mice without Causing Depression-Like Behaviour.

    Porter, Grace A / O'Connor, Jason C

    Neurology and neurobiology (Tallinn, Estonia)

    2021  Volume 4, Issue 3

    Abstract: Chronic stress is a well-known risk factor in major depressive disorder and disrupts the kynurenine and serotonin pathways of tryptophan metabolism. Here, we characterize the temporal central and peripheral changes in tryptophan metabolism and ... ...

    Abstract Chronic stress is a well-known risk factor in major depressive disorder and disrupts the kynurenine and serotonin pathways of tryptophan metabolism. Here, we characterize the temporal central and peripheral changes in tryptophan metabolism and concomitant depressive-like behavioural phenotype induced during the progression of chronic unpredictable stress (CUS). Mice were exposed to 0, 10, 20, or 30 days of CUS followed by a panel of behavioural assays to determine depressive-like phenotypes. Immediately after behavioural testing, plasma and brain tissue were collected for metabolic analysis. While anhedonia-like and anxiety-like behaviours were unaffected by stress, nesting behaviour and cognitive deficits became apparent in response to CUS exposure. While CUS caused a transient reduction in circulating quinolinic acid, no other tryptophan metabolites significantly changed in response to CUS. In the brain, tryptophan, kynurenine, picolinic acid, and 5-hydroxyindoleacetic acid concentrations were significantly elevated in CUS-exposed mice compared with non-stress control animals, while kynurenic acid, xanthurenic acid, and serotonin decreased in CUS-exposed mice. Metabolic turnover of serotonin to the major metabolite 5- hydroxyindoleacetic acid was markedly increased in response to CUS. These results suggest that CUS impairs hippocampal-dependent working memory and enhances nascent nesting behaviour in C57BL/6J male mice, and these behaviours are associated with increased brain kynurenine pathway metabolism leading to accumulation of picolinic acid and a significant reduction in serotonin levels.
    Language English
    Publishing date 2021-09-25
    Publishing country Estonia
    Document type Journal Article
    ISSN 2613-7828
    ISSN (online) 2613-7828
    DOI 10.31487/j.nnb.2021.03.03
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Are clinically unimportant findings qualified as benign in lumbar spine imaging reports? A content analysis of plain X-ray, CT and MRI reports.

    Farmer, Caitlin / Haas, Romi / Wallis, Jason / O'Connor, Denise / Buchbinder, Rachelle

    PloS one

    2024  Volume 19, Issue 3, Page(s) e0297911

    Abstract: Background: Lumbar spine diagnostic imaging reports may cause patient and clinician concern when clinically unimportant findings are not explicitly described as benign. Our primary aim was to determine the frequency that common, benign findings are ... ...

    Abstract Background: Lumbar spine diagnostic imaging reports may cause patient and clinician concern when clinically unimportant findings are not explicitly described as benign. Our primary aim was to determine the frequency that common, benign findings are reported in lumbar spine plain X-ray, computed tomography (CT) and magnetic resonance imaging (MRI) reports as either normal for age or likely clinically unimportant.
    Methods: We obtained 600 random de-identified adult lumbar spine imaging reports (200 X-ray, 200 CT and 200 MRI) from a large radiology provider. Only reports requested for low back pain were included. From the report text, one author extracted each finding (e.g., 'broad-based posterior disc bulge') and whether it was present or absent (e.g., no disc bulge) until data saturation was reached, pre-defined as a minimum of 50 reports and no new/similar findings in the last ten reports within each imaging modality. Two authors independently judged whether each finding was likely clinically unimportant or important. For each likely clinicially unimportant finding they also determined if it had been explicitly reported to be benign (expressed as normal, normal for age, benign, clinically unimportant or non-significant).
    Results: Data saturation was reached after coding 262 reports (80 X-ray, 82 CT, 100 MRI). Across all reports we extracted 3,598 findings. Nearly all reports included at least one clinically unimportant finding (76/80 (95%) X-ray, 80/82 (98%) CT, 99/100 (99%) MRI). Over half of the findings (n = 2,062, 57%; 272 X-Ray, 667 CT, 1123 MRI) were judged likely clinically unimportant. Most likely clinically unimportant findings (90%, n = 1,854) were reported to be present on imaging (rather than absent) and of those only 18% (n = 331) (89 (35%) X-ray, 93 (16%) CT and 149 (15%) MRI) were explicitly reported as benign.
    Conclusion: Lumbar spine imaging reports frequently include findings unlikely to be clinically important without explicitly qualifying that they are benign.
    MeSH term(s) Adult ; Humans ; X-Rays ; Lumbar Vertebrae/diagnostic imaging ; Lumbar Vertebrae/pathology ; Tomography, X-Ray Computed ; Magnetic Resonance Imaging/methods ; Lumbosacral Region
    Language English
    Publishing date 2024-03-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0297911
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The Influence of Branched-Chain Amino Acid Supplementation on Fatigue and Tryptophan Metabolism After Acute and Chronic Exercise in Older Adults

    Ronna N Robbins / Tiffany Cortes / Jason C O'Connor / Rozmin Jiwani / Monica C Serra

    JMIR Research Protocols, Vol 12, p e

    Protocol for a Pilot Randomized Controlled Trial

    2023  Volume 52199

    Abstract: BackgroundFatigue is a strong predictor of negative health outcomes in older adults. Kynurenine, a metabolite of tryptophan, is strongly associated with fatigue. Reductions in fatigue are observed with exercise; however, exercise training does not ... ...

    Abstract BackgroundFatigue is a strong predictor of negative health outcomes in older adults. Kynurenine, a metabolite of tryptophan, is strongly associated with fatigue. Reductions in fatigue are observed with exercise; however, exercise training does not completely alleviate symptoms. Branched-chain amino acids (BCAAs) have been shown to have advantageous effects on exercise performance and compete with kynurenine for transport into the central nervous system. Thus, the combination of BCAA and exercise may exert synergized effects of mental and physical fatigue. Therefore, we hypothesize that BCAA added to exercise will shift kynurenine metabolism toward enhanced synthesis of kynurenic acid, thereby reducing fatigue. ObjectiveThis randomized, double-blind, placebo-controlled trial aims to compare the effects of acute (approximately 45 min) and chronic (8 wk) exercise with and without BCAA supplementation on mental and physical fatigue and assess whether the hypothesized outcomes are modulated by changes in kynurenine metabolism in 30 older adults (n=15, 50% per group). MethodsOlder adults (aged 60-80 y) who do not exercise >2 days per week and self-report fatigue (≥3 on a scale of 1-10) will be recruited. Participants will be randomized to either the exercise+BCAA group or exercise+placebo group. Participants will engage in high-volume, moderate-intensity, whole-body exercise training (aerobic and resistance exercise; either in-person or web-based sessions) 3 times per week for 8 weeks. In addition, participants will consume daily either 100 mg/kg body weight of BCAA (2:1:1 leucine:isoleucine:valine) or placebo (maltodextrin) throughout the 8-week intervention. BCAA and placebo powders will be identical in color and dissolved in 400 mL of water and 2.5 g of a calorie-free water flavor enhancer. Muscle biopsies will be collected before and after the intervention after a 12-hour fast to examine changes in the biomarkers of tryptophan metabolism and inflammation. Our primary outcomes include changes in mental and ...
    Keywords Medicine ; R ; Computer applications to medicine. Medical informatics ; R858-859.7
    Subject code 796
    Language English
    Publishing date 2023-11-01T00:00:00Z
    Publisher JMIR Publications
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Randomization to Treadmill Training Improves Physical and Metabolic Health in Association With Declines in Oxidative Stress in Stroke.

    Serra, Monica C / Hafer-Macko, Charlene E / Robbins, Ronna / O'Connor, Jason C / Ryan, Alice S

    Archives of physical medicine and rehabilitation

    2022  Volume 103, Issue 11, Page(s) 2077–2084

    Abstract: Objective: To investigate the effect of aerobic exercise vs control (stretching/balance) on inflammatory and oxidative stress biomarkers in stroke survivors and whether these changes are associated with improvements in physical and metabolic health.: ... ...

    Abstract Objective: To investigate the effect of aerobic exercise vs control (stretching/balance) on inflammatory and oxidative stress biomarkers in stroke survivors and whether these changes are associated with improvements in physical and metabolic health.
    Design: Randomized controlled trial.
    Setting: The general communities of Baltimore, Maryland, and Atlanta, Georgia.
    Participants: Two hundred forty-six older (>50 years), chronic (>6 months) survivors of stroke (N=246) with hemiparetic gait were recruited, with 51 completing pre-intervention testing and 39 completing postintervention testing. Participants were required to have completed all conventional physical therapy and be capable of walking 3 minutes on a treadmill (N=246).
    Intervention: Participants completed 6 months of 2 times/wk stretching or balance (ST; n=19) or 3 times/wk aerobic treadmill rehabilitation (TM; n=20;).
    Main outcome measure(s): Peak oxygen uptake rate (V̇o
    Results: Physical function and metabolic health parameters tended to improve after TM but not ST (ST vs TM: V̇o
    Conclusions: Six months of TM tends to be associated with increased functional capacity and reduced oxidative stress in chronic stroke survivors. Our findings identify potentially modifiable systemic markers of inflammation and oxidative stress important to stroke rehabilitation and provide potential targets for novel therapeutics in future studies.
    MeSH term(s) Humans ; Biomarkers ; Exercise Therapy ; Insulins ; Oxidative Stress ; Random Allocation ; Stroke ; Stroke Rehabilitation ; Walking/physiology ; Middle Aged
    Chemical Substances Biomarkers ; Insulins
    Language English
    Publishing date 2022-07-12
    Publishing country United States
    Document type Journal Article ; Randomized Controlled Trial ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 80057-0
    ISSN 1532-821X ; 0003-9993
    ISSN (online) 1532-821X
    ISSN 0003-9993
    DOI 10.1016/j.apmr.2022.06.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Long-term benefits of hematopoietic stem cell-based macrophage/microglia delivery of GDNF to the CNS in a mouse model of Parkinson's disease.

    Ge, Guo / Sivasubramanian, Barath P / Geng, Bill D / Zhao, Shujie / Zhou, Qing / Huang, Gang / O'Connor, Jason C / Clark, Robert A / Li, Senlin

    Gene therapy

    2024  

    Abstract: Glial cell line-derived neurotrophic factor (GDNF) protects dopaminergic neurons in various models of Parkinson's disease (PD). Cell-based GDNF gene delivery mitigates neurodegeneration and improves both motor and non-motor functions in PD mice. As PD is ...

    Abstract Glial cell line-derived neurotrophic factor (GDNF) protects dopaminergic neurons in various models of Parkinson's disease (PD). Cell-based GDNF gene delivery mitigates neurodegeneration and improves both motor and non-motor functions in PD mice. As PD is a chronic condition, this study aims to investigate the long-lasting benefits of hematopoietic stem cell (HSC)-based macrophage/microglia-mediated CNS GDNF (MMC-GDNF) delivery in an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model. The results indicate that GDNF treatment effectively ameliorated MPTP-induced motor deficits for up to 12 months, which coincided with the protection of nigral dopaminergic neurons and their striatal terminals. Also, the HSC-derived macrophages/microglia were recruited selectively to the neurodegenerative areas of the substantia nigra. The therapeutic benefits appear to involve two mechanisms: (1) macrophage/microglia release of GDNF-containing exosomes, which are transferred to target neurons, and (2) direct release of GDNF by macrophage/microglia, which diffuses to target neurons. Furthermore, the study found that plasma GDNF levels were significantly increased from baseline and remained stable over time, potentially serving as a convenient biomarker for future clinical trials. Notably, no weight loss, altered food intake, cerebellar pathology, or other adverse effects were observed. Overall, this study provides compelling evidence for the long-term therapeutic efficacy and safety of HSC-based MMC-GDNF delivery in the treatment of PD.
    Language English
    Publishing date 2024-04-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 1191036-7
    ISSN 1476-5462 ; 0969-7128
    ISSN (online) 1476-5462
    ISSN 0969-7128
    DOI 10.1038/s41434-024-00451-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: COVID-19-Associated Acute Kidney Injury and Longitudinal Kidney Outcomes.

    Aklilu, Abinet M / Kumar, Sanchit / Nugent, James / Yamamoto, Yu / Coronel-Moreno, Claudia / Kadhim, Bashar / Faulkner, Sophia C / O'Connor, Kyle D / Yasmin, Farah / Greenberg, Jason H / Moledina, Dennis G / Testani, Jeffrey M / Wilson, F Perry

    JAMA internal medicine

    2024  Volume 184, Issue 4, Page(s) 414–423

    Abstract: Importance: COVID-19 infection is associated with a high incidence of acute kidney injury (AKI). Although rapid kidney function decline has been reported in the first few months after COVID-19-associated AKI (COVID-AKI), the longer-term association of ... ...

    Abstract Importance: COVID-19 infection is associated with a high incidence of acute kidney injury (AKI). Although rapid kidney function decline has been reported in the first few months after COVID-19-associated AKI (COVID-AKI), the longer-term association of COVID-AKI with kidney function remains unknown.
    Objective: To assess long-term kidney outcomes of patients who had COVID-19-associated AKI.
    Design, setting, and participants: This was a retrospective longitudinal multicenter cohort study conducted in a large hospital system using electronic health records data on adult hospitalized patients with AKI and COVID-19 or other illnesses. Included patients were hospitalized during the COVID-19 pandemic (March 2020-June 2022), were screened for SARS-CoV-2, had AKI, and survived to discharge, or had been hospitalized during the 5 years before the pandemic (October 2016-January 2020), had a positive influenza A or B test result, had AKI, and survived to discharge. Patients were followed up for a maximum of 2 years after hospital discharge. Data analyses were performed from December 2022 to November 2023.
    Exposure: COVID-19 and influenza.
    Main outcomes and measures: The primary outcome was major adverse kidney events (MAKE), defined as a composite of mortality and worsened kidney function (estimated glomerular filtration rate [eGFR] decline by ≥25% from discharge eGFR or kidney failure requiring dialysis). Multivariable time-to-event analyses were performed to compare MAKE between individuals with COVID-AKI and those who had AKI associated with other illnesses hospitalized during the same period. For further comparison, this outcome was assessed for a historic cohort of patients with influenza-associated AKI.
    Results: The study cohort included 9624 hospitalized patients (mean [SD] age, 69.0 [15.7] years; 4955 [51.5%] females) with AKI, including 987 patients with COVID-AKI, 276 with influenza-associated AKI, and 8361 with AKI associated with other illnesses (other-AKI). Compared with the other 2 groups, patients with COVID-19-associated AKI were slightly younger in age, had a higher baseline eGFR, worse baseline comorbidity scores, higher markers of illness severity, and longer hospital stay. Compared with the other-AKI group, the COVID-AKI group had lower MAKE (adjusted hazard ratio [aHR], 0.67; 95% CI, 0.59-0.75) due to lower all-cause mortality (aHR, 0.31; 95% CI, 0.24-0.39) and lower rates of worsened kidney function (aHR, 0.78; 95% CI, 0.69-0.88).
    Conclusions and relevance: The findings of this multicenter cohort study indicate that survivors of hospitalization with COVID-AKI experience lower rates of MAKE, long-term kidney function decline, and mortality compared with patients with AKI associated with other illnesses.
    MeSH term(s) Adult ; Female ; Humans ; Aged ; Male ; Cohort Studies ; Retrospective Studies ; Pandemics ; Influenza, Human ; COVID-19/complications ; COVID-19/epidemiology ; SARS-CoV-2 ; Kidney ; Acute Kidney Injury/epidemiology ; Acute Kidney Injury/etiology ; Risk Factors
    Language English
    Publishing date 2024-02-26
    Publishing country United States
    Document type Multicenter Study ; Journal Article
    ZDB-ID 2699338-7
    ISSN 2168-6114 ; 2168-6106
    ISSN (online) 2168-6114
    ISSN 2168-6106
    DOI 10.1001/jamainternmed.2023.8225
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Brain derived neurotrophic factor deficiency exacerbates inflammation-induced anhedonia in mice.

    Parrott, Jennifer M / Porter, Grace A / Redus, Laney / O'Connor, Jason C

    Psychoneuroendocrinology

    2021  Volume 134, Page(s) 105404

    Abstract: Brain-derived neurotrophic factor (BDNF) is implicated in the pathology of major depression and influences the inflammatory response. Prolonged immune system activation can cause depression symptoms, and individuals with low BDNF expression may be ... ...

    Abstract Brain-derived neurotrophic factor (BDNF) is implicated in the pathology of major depression and influences the inflammatory response. Prolonged immune system activation can cause depression symptoms, and individuals with low BDNF expression may be vulnerable to inflammation-induced depression. We tested the hypothesis that BDNF deficient mice are vulnerable to the induction of depressive-like behavior following peripheral immune challenge. BDNF heterozygous (BDNF
    Language English
    Publishing date 2021-09-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 197636-9
    ISSN 1873-3360 ; 0306-4530
    ISSN (online) 1873-3360
    ISSN 0306-4530
    DOI 10.1016/j.psyneuen.2021.105404
    Database MEDical Literature Analysis and Retrieval System OnLINE

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