scholarly journals An ancient polymorphic regulatory region within the BDNF gene associated with obesity modulates anxiety-like behaviour in mice and humans.

2021 ◽  
Author(s):  
Andrew R McEwan ◽  
Benjamin Hing ◽  
Johanna Erickson ◽  
Yvonne Turnbull ◽  
Mirela Delibegovic ◽  
...  
Keyword(s):  
Mouse Genome ◽  
Cohort Analysis ◽  
Regulatory Region ◽  
Human Populations ◽  
Mrna Levels ◽  
Primary Cells ◽  
Bdnf Gene ◽  
Bdnf Mrna ◽  
Marble Burying

Obesity and anxiety are morbidities notable for their increased impact on society during the recent COVID-19 pandemic. Understanding the mechanisms governing susceptibility to these conditions will increase quality of life and our resilience to future pandemics. In the current study we explored the function of a highly conserved regulatory region (BE5.1) within the BDNF gene that harbours a polymorphism strongly associated with obesity (rs10767664; p=4.69x10-26). Analysis in primary cells suggested that the major T-allele of BE5.1 was an enhancer whereas the obesity associated A-allele was not. However, CRISPR/CAS9 deletion of BE5.1 from the mouse genome (BE5.1KO) produced no significant effect on the expression of BDNF transcripts in the hypothalamus, no change in weight gain after 28 days and only a marginally significant increase in food intake. Nevertheless, transcripts were significantly increased in the amygdala of female mice and elevated zero maze and marble burying tests demonstrated a significant increase in anxiety-like behaviour that could be reversed by diazepam. Consistent with these observations, human GWAS cohort analysis demonstrated a significant association between rs10767664 and anxiousness in human populations. Intriguingly, interrogation of the human GTEx eQTL database demonstrated no effect on BDNF mRNA levels associated with rs10767664 but a highly significant effect on BDNF-antisense (BDNF-AS) gene expression and splicing suggesting a possible mechanism. We discuss our findings within the context of the known function and regulation of BDNF in obesity and anxiety whilst exploring the validity of interrogating GWAS data using comparative genomics and functional analysis using CRISPR genome editing in mice.

scholarly journals Altered mRNA Levels of Stress-Related Peptides in Mouse Hippocampus and Caudate-Putamen in Withdrawal after Long-Term Intermittent Exposure to Tobacco Smoke or Electronic Cigarette Vapour

2021 ◽  
Vol 22 (2) ◽  
pp. 599
Author(s):  
Lucia Carboni ◽  
Luisa Ponzoni ◽  
Daniela Braida ◽  
Mariaelvina Sala ◽  
Cecilia Gotti ◽  
...  
Keyword(s):  
Public Health Problem ◽  
Mrna Levels ◽  
Obsessive Compulsive ◽  
Bdnf Mrna ◽  
Object Recognition Test ◽  
Caudate Putamen ◽  
Molecular Alterations ◽  
Marble Burying ◽  
Cigarette Withdrawal

Nicotine addiction is a severe public health problem. The aim of this study was to investigate the alterations in key neurotransmissions after 60 days of withdrawal from seven weeks of intermittent cigarette smoke, e-cigarette vapours, or an e-cigarette vehicle. In the nicotine withdrawal groups, increased depressive and anxiety/obsessive–compulsive-like behaviours were demonstrated in the tail suspension, sucrose preference and marble burying tests. Cognitive impairments were detected in the spatial object recognition test. A significant increase in Corticotropin-releasing factor (Crf) and Crf1 mRNA levels was observed, specifically after cigarette withdrawal in the caudate-putamen nucleus (CPu). The nociceptin precursor levels were reduced by cigarette (80%) and e-cigarette (50%) withdrawal in the CPu. The delta opioid receptor showed a significant reduction in the hippocampus driven by the exposure to an e-cigarette solubilisation vehicle, while the mRNA levels doubled in the CPu of mice that had been exposed to e-cigarettes. Withdrawal after exposure to e-cigarette vapour induced a 35% Bdnf mRNA decrease in the hippocampus, whereas Bdnf was augmented by 118% by cigarette withdrawal in the CPu. This study shows that long-term withdrawal-induced affective and cognitive symptoms associated to lasting molecular alterations in peptidergic signalling may determine the impaired neuroplasticity in the hippocampal and striatal circuitry.

Expression of the BDNF gene in the developing visual system of the chick

Development ◽  
1994 ◽  
Vol 120 (6) ◽  
pp. 1643-1649 ◽  
Author(s):  
K.H. Herzog ◽  
K. Bailey ◽  
Y.A. Barde
Keyword(s):  
Visual System ◽  
Ganglion Cells ◽  
Mrna Levels ◽  
Retinal Ganglion ◽  
Bdnf Gene ◽  
Bdnf Mrna ◽  
Optic Stalk ◽  
Copy Numbers ◽  
Activity Dependent

Using a sensitive and quantitative method, the mRNA levels of brain-derived neurotrophic factor (BDNF) were determined during the development of the chick visual system. Low copy numbers were detected, and BDNF was found to be expressed in the optic tectum already 2 days before the arrival of the first retinal ganglion cell axons, suggesting an early role of BDNF in tectal development. After the beginning of tectal innervation, BDNF mRNA levels markedly increased, and optic stalk transection at day 4 (which prevents subsequent tectal innervation) was found to reduce the contralateral tectal levels of BDNF mRNA. Comparable reductions were obtained after injection of tetrodotoxin into one eye, indicating that, already during the earliest stages of target encounter in the CNS, the degree of BDNF gene expression is influenced by activity-dependent mechanisms. BDNF mRNA was also detected in the retina itself and at levels comparable to those found in the tectum. Together with previous findings indicating that BDNF prevents the death of cultured chick retinal ganglion cells, these results support the idea that the tightly controlled expression of the BDNF gene might be important in the co-ordinated development of the visual system.

scholarly journals Hyperglycemia and Hypercapnia Suppress BDNF Gene Expression in Vulnerable Regions after Transient Forebrain Ischemia in the Rat

1997 ◽  
Vol 17 (12) ◽  
pp. 1303-1308 ◽  
Author(s):  
H. Uchino ◽  
O. Lindvall ◽  
B. K. Siesjö ◽  
Z. Kokaia
Keyword(s):  
Pyramidal Neurons ◽  
Granule Cells ◽  
Hippocampal Formation ◽  
Cingulate Cortex ◽  
Mrna Levels ◽  
Forebrain Ischemia ◽  
Bdnf Gene ◽  
Bdnf Mrna ◽  
Transient Forebrain Ischemia

Preischemic hyperglycemia or superimposed hypercapnia exaggerates brain damage caused by transient forebrain ischemia. Because high regional levels of brain-derived neurotrophic factor (BDNF) protein correlate with resistance to ischemic damage, we studied the expression of BDNF mRNA using in situ hybridization in rats subjected to 10 minutes of forebrain ischemia under normoglycemic, hyperglycemic, or hypercapnic conditions. Compared with normoglycemic animals, the increase of BDNF mRNA in dentate granule cells was attenuated and that in CA3 pyramidal neurons completely prevented in hyperglycemic rats. No ischemia-induced increases of BDNF mRNA levels in the hippocampal formation were detected in hypercapnic animals. Hyperglycemic and hypercapnic rats showed transiently decreased expression of BDNF mRNA levels in the cingulate cortex, which was not observed in normoglycemic animals. The results suggest that suppression of the BDNF gene might contribute to the increased vulnerability of the CA3 region and cingulate cortex in hyperglycemic and hypercapnic animals.

Urban and rural millennials: Heterogeneity of the young adult generation

2019 ◽  
pp. 5-28
Author(s):  
Vadim V. Radaev
Keyword(s):  
Coming Out ◽  
Generational Differences ◽  
Cohort Analysis ◽  
Social Indicators ◽  
Well Being ◽  
Generational Cohort ◽  
Rural Infrastructure ◽  
Sociological Approach ◽  
Monitoring Survey

A sociological approach towards the generational cohort analysis is developed. A special emphasis is made upon the youngest adult generation of millennials coming out of their adolescence in the 2000s. A broad range of social indicators is used for empirical exploration of intra-generational differences between urban and rural millennials. Data were collected from the annual Russian Longitudinal Monitoring Survey (RLMS-HSE) in 2003—2016. Numerous significant differences have been revealed with regard to the educational level, family planning, use of modern gadgets and digital technologies, commitment to healthy lifestyles, and some values. Some practices are more widely spread among rural millennials, whereas other practices are more characteristic of urban millennials. Most of revealed differences are explained by the lower level of material well-being of rural millennials and lower quality of rural infrastructure.

scholarly journals Glatiramer Acetate Treatment in Multiple Sclerosis-Associated Fatigue—Beneficial Effects on Self-Assessment Scales But Not on Molecular Markers

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 393
Author(s):  
Oliver Neuhaus ◽  
Wolfgang Köhler ◽  
Florian Then Bergh ◽  
Wolfgang Kristoferitsch ◽  
Jürgen Faiss ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Neurotrophic Factors ◽  
Common Symptom ◽  
Mrna Levels ◽  
Open Label ◽  
Immunological Parameters ◽  
Beneficial Effects

Although fatigue is a common symptom in multiple sclerosis (MS), its pathomechanisms are incompletely understood. Glatiramer acetate (GA), an immunomodulatory agent approved for treatment of relapsing-remitting MS (RRMS), possesses unique mechanisms of action and has been shown to exhibit beneficial effects on MS fatigue. The objective of this study was to correlate clinical, neuropsychological, and immunological parameters in RRMS patients with fatigue before and during treatment with GA. In a prospective, open-label, multicenter trial, 30 patients with RRMS and fatigue were treated with GA for 12 months. Inclusion criterion was the presence of fatigue as one of the most frequent and disabling symptoms. Before and during treatment, fatigue was assessed using the Fatigue Severity Scale (FSS), the MS-FSS, and the Modified Fatigue Impact Scale (MFIS). In addition, fatigue and quality of life were assessed using the Visual Analog Scales (VAS). Laboratory assessments included screening of 188 parameters using real-time PCR microarrays followed by further analysis of several cytokines, chemokines, and neurotrophic factors. Fatigue self-assessments were completed in 25 patients. After 12 months of treatment with GA, 13 of these patients improved in all three scales (with the most prominent effects on the MFIS), whereas 5 patients had deteriorated. The remaining 7 patients exhibited inconsistent effects within the three scales. Fatigue and overall quality of life had improved, as assessed via VAS. Laboratory assessments revealed heterogeneous mRNA levels of cytokines, chemokines, and neurotrophic factors. In conclusion, we were not able to correlate clinical and molecular effects of GA in patients with RRMS and fatigue.

Urbanization, housing and environmental quality indicators

2015 ◽  
Vol 11 (2) ◽  
pp. 51-56
Author(s):  
A Oladele
Keyword(s):  
Quality Indicators ◽  
Environmental Quality ◽  
Power Supply ◽  
Housing Stock ◽  
Housing Quality ◽  
Human Populations ◽  
Urbanization Process ◽  
Reconnaissance Survey ◽  
Urban Settlements

The migration of human populations from rural to urban settlements known as urbanization in its most basic sense suggests an improvement in various facets of life. Urbanization ideally should also imply an enhancement of housing quality and other components of human settlements such as power supply, portable water, good roads, proper refuse and sewage disposal facilities, maintenance of ecological balance and a reduction in environmental pollution. Globally, the urbanization process has occurred in a disorganized and nearly uncontrollable manner. The spontaneity in growth of urban settlements has affected negatively several components of the urban fabric such that these components (previously mentioned) are either severely inadequate or non-existent in majority of instances where urbanization has taken place. Arguably, the success of any urbanization process can be measured by the quality of the environments produced and the housing stock found within such environments. This paper seeks to identify and evaluate the components of urban settlements that can be used as indices for establishing quality of our housing, environments and urban clusters particularly for the Nigerian context. The research methodology is a reconnaissance survey, field observation and comparison of four main areas within Ido Local Government Area of Ibadan, Oyo State, namely Apete, Elebu, Elenusonso and Ologuneru.Key words: Urbanization, Environmental quality indicators.

scholarly journals Prevalence of Function-Limiting Late Effects in Hodgkin Lymphoma Survivors

2020 ◽  
Author(s):  
Nabela Enam ◽  
Kathy Chou ◽  
Michael D. Stubblefield
Keyword(s):  
Quality Of Life ◽  
Hodgkin Lymphoma ◽  
Musculoskeletal Pain ◽  
Late Effects ◽  
Cohort Analysis ◽  
Cancer Rehabilitation ◽  
Secondary Malignancy ◽  
Major Function ◽  
Rehabilitation Clinic

AbstractObjectiveTo define the prevalence of neuromuscular, musculoskeletal, pain, visceral, oncologic and other late effects impacting function and quality of life in Hodgkin lymphoma(HL) survivors presenting to an outpatient cancer rehabilitation clinic.DesignA retrospective cohort analysis.SettingOutpatient cancer rehabilitation clinic.ParticipantsOne hundred consecutive HL survivors.InterventionsNone.Main Outcome MeasuresThe prevalence of neuromuscular, musculoskeletal, pain, visceral, oncologic and other late effects contributing to functional impairment and disability in HL survivors.ResultsAmong the 100 HL survivors, 43% received chemotherapy, 94% radiation therapy, and 38% a combination of chemotherapy and radiation for initial treatment. Nearly all HL survivors were diagnosed with myelopathy (83%), radiculo-plexopathy (93%), mononeuropathy (95%) and localized myopathy (93%). Musculoskeletal sequelae were extremely common and included dropped head syndrome (83%), cervicalgia (79%), shoulder girdle dysfunction (73%), and dysphagia (42%). Visceral disorders were also common and included cardiovascular (70%), pulmonary (44%), endocrine (63%), gastrointestinal (29%), and genitourinary (11%) dysfunction. Lymphedema affected 21% of survivors and 30% had a history of a secondary malignancy. Pain (71%), fatigue (45%), and dyspnea (43%) were major function-limiting impairments. Nearly all (95%) of survivors were referred to at least one therapy discipline including physical therapy, occupational therapy, speech and language pathology and/or lymphedema therapy.ConclusionNeuromuscular, musculoskeletal, pain, visceral, oncologic and other late effectsare extremely common in HL survivors seeking physiatric evaluation. Multiple function-limiting disorders can co-exist in HL survivors with the potential to severely compromise function and quality of life. Safe and effective rehabilitation may depend on the physiatrist’s ability to identify, evaluate and manage the multitude of complex and often interrelated functional late effects seen in HL survivors.

Transanal Ileal Pouch-Anal Anastomosis for Ulcerative Colitis has Comparable Long-Term Functional Outcomes to Transabdominal Approach: A Multicentre Comparative Study

2019 ◽  
Vol 14 (6) ◽  
pp. 726-733 ◽  
Author(s):  
Pramodh Chandrasinghe ◽  
Michele Carvello ◽  
Karin Wasmann ◽  
Caterina Foppa ◽  
Pieter Tanis ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ulcerative Colitis ◽  
Functional Outcomes ◽  
Ileal Pouch ◽  
Cohort Analysis ◽  
Ileal Pouch Anal Anastomosis ◽  
Global Quality Of Life ◽  
Anal Anastomosis

Abstract Background The transanal approach to ileal pouch-anal anastomosis [Ta-IPAA] provides better access to the lower pelvis with lower short-term morbidity in ulcerative colitis [UC]. The aim of this study was to assess the long-term functional outcomes after Ta-IPAA vs transabdominal IPAA [Abd-IPAA] in UC. Methods A multicentre cohort analysis was performed between March 2002 and September 2017. Patient characteristics, surgical details and postoperative outcomes were compared. CGQL [Cleveland global quality of life] score at 12 months with a functioning pouch was considered the primary end point. Results A total of 374 patients [100 Ta-IPAA vs 274 Abd-IPAA] were included. Ta-IPAA demonstrated a comparable overall quality of life [CGQL score] to Abd-IPAA [0.75 ± 0.11 vs 0.71 ± 0.14; respectively, p = 0.1]. Quality of life [7.71 ± 1.17 vs 7.30 ± 1.46; p = 0.04] and energy-level items [7.16 ± 1.52 vs 6.66 ± 1.68; p = 0.03] were significantly better after Ta-IPAA, while the quality of health item was comparable [7.68 ± 1.26 vs 7.64 ± 1.44; p = 0.96]. Analysis excluding anastomotic leaks did not change the overall CGQL scores. Stool frequencies [>10/24 h: 22% vs 21%; p = 1.0] and the rate of a single episode of major incontinence during the following 12-month period [27% vs 26%; p = 0.89] were similar. The differences in 30-day morbidity rates [33% vs 41%; p = 0.2] and anastomotic leak rates were not significant [6% vs 13%; p = 0.09]. Conclusions This study provides evidence of comparable long-term functional outcome and quality of life after Ta-IPAA and Abd-IPAA for UC.

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