Plasma BDNF Research Articles

Brain-Derived Neurotrophic Factor as a Potential Mediator of the Beneficial Effects of Myo-Inositol Supplementation during Suckling in the Offspring of Gestational-Calorie-Restricted Rats.

This study aims to investigate the potential mechanisms underlying the protective effects of myo-inositol (MI) supplementation during suckling against the detrimental effects of fetal energy restriction described in animal studies, particularly focusing on the potential connections with BDNF signaling. Oral physiological doses of MI or the vehicle were given daily to the offspring of control (CON) and 25%-calorie-restricted (CR) pregnant rats during suckling. The animals were weaned and then fed a standard diet until 5 months of age, when the diet was switched to a Western diet until 7 months of age. At 25 days and 7 months of age, the plasma BDNF levels and mRNA expression were analyzed in the hypothalamus and three adipose tissue depots. MI supplementation, especially in the context of gestational calorie restriction, promoted BDNF secretion and signaling at a juvenile age and in adulthood, which was more evident in the male offspring of the CR dams than in females. Moreover, the CR animals supplemented with MI exhibited a stimulated anorexigenic signaling pathway in the hypothalamus, along with improved peripheral glucose management and enhanced browning capacity. These findings suggest a novel connection between MI supplementation during suckling, BDNF signaling, and metabolic programming, providing insights into the mechanisms underlying the beneficial effects of MI during lactation.

Transcutaneous auricular vagus nerve stimulation for post-stroke depression: A double-blind, randomized, placebo-controlled trial

BackgroundIt is a well-established fact that post-stroke depression (PSD) is a prevalent condition that affects a significant proportion of individuals who have suffered a stroke. Hence, our research endeavors to explore the safety, efficacy and the potential molecular mechanism of transcutaneous auricular vagus nerve stimulation (ta-VNS) for the treatment of depression in PSD patients by conducting a double-blind, sham-controlled, randomized trial. MethodsPatients who had experienced strokes and exhibited depressive symptoms, with a Hamilton Depression Scale (HAMD-17) score of ≥8 and met the DSM-IV criteria, were diagnosed with PSD. A volunteer sample of participants (N = 80) were randomly divided into either the ta-VNS group (which received ta-VNS in addition to conventional treatment) or the control group (which received conventional treatment only), in a 1:1 ratio. The effectiveness of the interventions was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD-17), Zung Self-Rating Depression Scale (SDS), and Barthel Index (BI) scores. Furthermore, Plasma BDNF, CREB1, and 5-HT levels were measured before and after treatment. ResultsThe concomitant application of ta-VNS demonstrated a remarkable reduction in HAMD-17 and SDS scores, leading to noteworthy enhancements in patients' daily functioning, as evidenced by improved activities of daily living, at all assessed time points, in contrast to the control group (p < 0.0001). Notably, the ta-VNS group exhibited superior effects in modulating the measured neurotrophic biomarkers when compared to the control group (p < 0.05). ConclusionsThe synergistic approach of combining ta-VNS with conventional treatment has demonstrated remarkable efficacy and tolerability in managing depression following a stroke.

Effects of combined dietary intervention and physical-cognitive exercise on cognitive function and cardiometabolic health of postmenopausal women with obesity: a randomized controlled trial

BackgroundPostmenopausal women with obesity are markedly at risk of cognitive impairment and several health issues. Emerging evidence demonstrated that both diet and exercise, particularly physical-cognitive exercise are involved in cognitive and health benefits. However, the comparative effect of diet, exercise, and combined interventions in postmenopausal women with obesity on cognition and cardiometabolic health is still lacking. Identifying the effective health promotion program and understanding changes in cardiometabolic health linking these interventions to cognition would have important medical implications. This RCT aimed to examine the effect of single and combined interventions of diet and exercise on cognitive function and cardiometabolic health in postmenopausal women with obesity.MethodsNinety-two postmenopausal women with obesity were randomly assigned to diet group (intermittent fasting 2 days/week, 3 months), exercise group (physical-cognitive exercise 3 days/week, 3 months), combined group, or control group (n = 23/group). All cognitive outcomes and cardiometabolic outcomes were measured at baseline and post-3 months. Primary outcomes were executive functions, memory, and plasma BDNF levels. Secondary outcomes were global cognition, attention, language domain, plasma adiponectin levels, IL-6 levels, metabolic parameters, and physical function.ResultsAt the end of the 3-month intervention, the exercise and combined group demonstrated significant memory improvement which was accompanied by significant improvements in plasma BDNF level, insulin levels, HOMA-IR, %body fat, and muscle strength when compared to controls (p < 0.05). Only the combined intervention group demonstrated a significant improvement in executive function and increased plasma adiponectin levels when compared to control (p < 0.05). Surprisingly, no cognitive improvement was observed in the diet group (p > 0.05). Significant reduction in cholesterol levels was shown in the diet and combined groups when compared to controls (p < 0.05). Among the three intervention groups, there were no significant differences in all cognitive outcomes and cardiometabolic outcomes (p > 0.05). However, all three intervention groups showed significant improvements in plasma BDNF levels, weight, BMI, WHR, fat mass, and predicted VO2 max, when compared to control (p < 0.05).ConclusionThese findings suggest that combined physical-cognitive exercise and dietary intervention are promising interventions to improve cognition and obesity-related complications of postmenopausal women with obesity.Trial registrationNCT04768725 (https://clinicaltrials.gov) 24th February 2021.

Changes in Plasma TPH2, GDNF, Trk-b, BDNF, and proBDNF in People Who Died by Suicide.

Recent studies have shown that neuropeptides and neurotrophic factors may be involved in the pathophysiological mechanisms of suicide. However, the current research on this aspect is still insufficient. Our study aimed to explore the biological patterns of suicide deaths, including levels of BDNF, proBDNF, BDNF/proBDNF, Trk-b, GDNF, and TPH2. The researchers selected 25 normal control patients matched by age with 30 suicide deaths. We used enzyme-linked immunosorbent assays to detect the levels of BDNF, proBDNF, BDNF/proBDNF, Trk-b, GDNF, and TPH2 in the plasma of suicide and control subjects. proBDNF, BDNF/proBDNF, Trk-b, GDNF, and TPH2 levels are shown as the median (25th-75th percentile). BDNF levels are shown as the mean (standard error of the mean). (1) The levels of plasma TPH2 and proBDNF in people who died by suicide were significantly higher than those in the control group. (2) The plasma levels of GDNF and BDNF/proBDNF in the suicide group were obviously lower than those in the control group. (3) There was no significant difference in plasma BDNF or Trk-b concentrations between the suicide group and the control group.Plasma TPH2, GDNF, and proBDNF levels are related to suicide. Plasma neurotrophic factor markers may predict suicide risk.

Reduced Plasma BDNF Levels in Normal Tension Glaucoma Compared to Open Angle Glaucoma.

The study suggests that a low level of systemic BDNF may contribute to the pathogenesis of glaucoma in an IOP-independent manner. To evaluate differences in systemic brain-derived neurotrophic factor (BDNF) levels between primary open angle glaucoma (POAG) patients and normal tension glaucoma (NTG) patients. This study collected blood samples from 260 NTG patients, 220 age-matched POAG patients, and 120 age-matched cataract patients (as controls). BDNF levels were measured with an antibody-conjugated bead assay system (Luminex). We found that plasma BDNF levels in the NTG group were significantly lower than in the POAG and cataract control groups. There was no significant difference between the POAG and cataract groups. This result suggests that a low level of systemic BDNF may contribute to the pathogenesis of glaucoma in an IOP-independent manner.

Elevated brain derived neurotrophic factor in plasma and interleukin-6 levels in cerebrospinal fluid in meningitis compared to cerebral malaria

Neurological infections, such as Cerebral malaria (CM) and meningitis are associated with high mortality and in survivors, particularly young children, persistent neurologic deficits often remain. As brain inflammation plays a role in the development of these neurological sequelae, multiplex assays were used to assess a select set of immune mediators in both plasma and cerebrospinal fluid (CSF) from Zambian children with neurological infections.Both CM and meningitis patients showed high levels of markers for vascular inflammation, such as soluble ICAM-1 and angiopoietins. Although high levels of angiopoietin 1 and angiopoietin 2 were found in the meningitis group, their levels in the CSF were low and did not differ.As expected, there were high levels of cytokines and notably a significantly elevated IL-6 level in the CSF of the meningitis group. Interestingly, although elevated levels BDNF were found, BDNF levels were significantly higher in plasma of the meningitis group but similar in the CSF.The striking differences in plasma BDNF and IL-6 levels in the CSF point to markedly different neuro-pathological processes. Therefore, further investigations in the role of both IL-6 and BDNF in the neurological outcomes are needed.

Effect of milnacipran on brain‑derived neurotrophic factor and oxidative stress biomarkers in patients of major depressive disorder.

Emerging hypotheses in the pathophysiology of major depressive disorder (MDD) suggest important role of neurotrophic factors and oxidative stress. This study assessed the effect of milnacipran (a dual serotonin‑noradrenaline reuptake inhibitor) on brain‑derived neurotrophic factor (BDNF) and oxidative stress biomarkers i.e., malondialdehyde (MDA), glutathione‑s‑ transferase (GST) and glutathione reductase (GR) in patients of MDD. Thirty patients (aged 18 to 60 years) with MDD diagnosed by DSM‑IV criteria, with Hamilton Depression Rating scale (HAM‑D) score ≥ 14 were included in the study. Patients were given milnacipran in the doses of 50‑100 mg once daily. Patients were followed up for 12 weeks. HAM‑D score at the start of treatment was 17.8±1.7 which significantly reduced to 8.9±3.1 at 12 weeks of treatment. In responders, the plasma BDNF levels increased significantly at 12 weeks post treatment. There was no significant change in the pre‑ and post‑treatment values of oxidative stress parameters (MDA, GST and GR) after 12 week treatment. Milnacipran is effective and well tolerated in MDD patients, and its therapeutic response is associated with an increase in plasma BDNF levels. However, milnacipran did not affect oxidative stress biomarkers.

Neurophysiological determinants of occupational stress and burnout

IntroductionResearch results show that one of the greatest health challenges of the 21st century, especially in developed countries, is becoming the fight against the effects of living too fast, including the fight against occupational stress and burnout.&#x0D; Aim of the study&#x0D; The purpose of this article is to elucidate the neurophysiological determinants of occupational stress and burnout, including ocupational, including through the path of research review and the development of computational models based on artificial intelligence.&#x0D; Materials and methods&#x0D; A literature search was conducted in six bibliographic databases: PubMed, EBSCO, PEDro, Web of Science, Scopus and Google Scholar. Articles were searched in English using the following keywords: occupational stress, burnout, marker, electroencephalography, EEG, magnetic resonance imaging, MRI, fMRI, computed tomography, CT, positron emission tomography, PET, computational model, machine learning, artificial intelligence, virtual patient, digital twin and similar. Neurophysiological determinants of occupational stress and burnout as far as computational models of occupational stress and burnout were analysed and discussed.&#x0D; Results&#x0D; The best currently observed neurophysiological markers of occupational stress and burnout may currently be a combination of EEG analysis (alpha power (IAF, PAF), P300, ERP (VPP and EPN)), diagnostic PET imaging (ACC, insular cortex and hippocampus) and monitoring changes in cortisol, prolactin, adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH) and thyroid hormones, as well as plasma BDNF levels. In addition, ERPs (LPPs) are a marker significantly differentiating burnout from depression.&#x0D; Conclusions&#x0D; The combination of traditional clinimetric tests, the aforementioned neurophysiological tests and AI-based big data analysis will provide new classifiers, highly accurate results and new diagnostic methods.&#x0D;

Association between Psychopathological Symptoms and Aggression and Selected Biochemical Parameters in Adolescents with Behavioural and Emotional Disturbances.

Behavioural and emotional disturbances (F92.8) are the most recognized disorders in a developmental psychiatry. As the problem is still alarmingly increasing, the searches for their etiopathogenesis and more effective preventing and therapy methods are required. The aim of the study was to assess the association between the quality of life, some psychopathological features, concentrations of selected immunoprotective (brain-derived neurotrophin, BDNF), and endocrine (cortisol, F) factors while adolescent disturbances. The study was performed in 123 inpatients of a psychiatric ward with F92.8 diagnosis, aged 13-18 years. The complete patients' interview, physical examination, and routine laboratory tests, including serum F and BDNF tests, were performed. All patients completed standardized questionnaires to estimate: the severity of psychopathological symptoms (SCL-90), the level of aggression (Buss-Perry). The changes in the plasma BDNF and F concentrations were shown in patients raised in foster homes and institutions. The significantly lower BDNF was observed in youth from foster and suicide-experienced families. The more severe psychopathological symptoms, especially aggression and hostility, were found in these ones, who abused alcohol, attempted suicide, had lower self-esteem and cognitive processes, and were lacking safety in dysfunctional families.

Brain-Derived Neurotrophic Factor, Kynurenine Pathway, and Lipid-Profiling Alterations as Potential Animal Welfare Indicators in Dairy Cattle

Complete animal welfare evaluation in intensive farming is challenging. With this study, we investigate new biomarkers for animal physical and mental health by comparing plasma expression of biochemical indicators in dairy cows reared in three different systems: (A) semi-intensive free-stall, (B) non-intensive tie-stall, and (C) intensive free-stall. Additionally, protein levels of mature brain-derived neurotrophic factor (mBDNF) and its precursor form (proBDNF) and indoleamine 2,3-dioxygenase (IDO1) specific activity were evaluated in brain samples collected from 12 cattle culled between 73 and 138 months of age. Alterations in plasma lipid composition and in the kynurenine pathway of tryptophan metabolism were observed in the tie-stall-reared animals. The total plasma BDNF concentration was higher in tie-stall group compared to the two free-housing groups. Brain analysis of the tie-stall animals revealed a different mBDNF/proBDNF ratio, with a higher level of proBDNF (p < 0.001). Our data are similar to previous studies on animal models of depression, which reported that inhibition of the conversion of proBDNF in its mature form and/or elevated peripheral kynurenine pathway activation may underlie cerebral biochemical changes and induce depressive-like state behavior in animals.

An exploratory approach to identify microRNAs as circulatory biomarker candidates for epilepsy-associated psychiatric comorbidities in an electrical post-status epilepticus model

Patients with epilepsy have a high risk of developing psychiatric comorbidities, and there is a particular need for early detection of these comorbidities. Here, in an exploratory, hypothesis-generating approach, we aimed to identify microRNAs as potential circulatory biomarkers for epilepsy-associated psychiatric comorbidities across different rat models of epilepsy. The identification of distress-associated biomarkers can also contribute to animal welfare assessment. MicroRNA expression profiles were analyzed in blood samples from the electrical post-status epilepticus (SE) model. Preselected microRNAs were correlated with behavioral and biochemical parameters in the electrical post-SE model, followed by quantitative real-time PCR validation in three additional well-described rat models of epilepsy. Six microRNAs (miR-376a, miR-429, miR-494, miR-697, miR-763, miR-1903) were identified showing a positive correlation with weight gain in the early post-insult phase as well as a negative correlation with social interaction, saccharin preference, and plasma BDNF. Real-time PCR validation confirmed miR-203, miR-429, and miR-712 as differentially expressed with miR-429 being upregulated across epilepsy models. While readouts from the electrical post-SE model suggest different microRNA candidates for psychiatric comorbidities, cross-model analysis argues against generalizability across models. Thus, further research is necessary to compare the predictive validity of rodent epilepsy models for detection and management of psychiatric comorbidities.

How can ketamine be used to manage suicidal risk?

In France, suicidal behaviors remain a major public health issue. Depressed patients with suicidal ideation have more severe depressive symptoms, a more unfavorable disease course, and a greater number of suicide attempts than patients without suicidal ideation. Unfortunately, conventional antidepressants tend to be less effective in patients with suicidal tendencies than in those without. Nevertheless, promising advancements have emerged with the use of ketamine, which has shown significant and rapid efficacy in reducing the intensity of suicidal ideation in depressed patients within the first 72 h after its administration. Several mechanisms are potentially involved: (1) reduction of anhedonia. It has been demonstrated that ketamine reduces both anhedonia and suicidal ideation. In depressed patients, the reduction of anhedonia observed 2 h after ketamine administration is associated with metabolic changes in the anterior cingulate cortex involved in suicidal ideation; (2) activation of neuroplasticity cascades. The reduction in suicidal ideation within 24 h following ketamine administration is correlated with changes in plasma BDNF levels and is modulated by the Val66Met functional polymorphism of the BDNF gene. Moreover, preclinical and clinical studies have shown that ketamine induces functional and connectivity changes in the prefrontal and anterior cingulate regions, which are strongly implicated in suicidal behaviors; (3) reduction of inflammation. It is now widely accepted that suicidal behaviors are associated with low-grade inflammation, and with elevated quinolinic acid and reduced kynurenic acid levels. Interestingly, predictors of a reduction in suicidal ideation after ketamine infusion include initial severity of suicidal thoughts and depression, as well as baseline blood levels of kynurenic acid; (4) involvement of the opioidergic system. Post-mortem studies have indicated alterations in the opioidergic system related to suicidal behaviors. A recent study suggested that the antisuicidal effect of ketamine may depend on this system because naltrexone, an antagonist of mu opioid receptors, abolished the typical antidepressant effect and reduction in suicidal ideation observed following ketamine administration. In conclusion, ketamine exhibits promising potential in mitigating suicidal ideation - its effects are specific, rapid, albeit temporary. The suggested mechanisms driving its efficacy are multifaceted. Nevertheless, it is yet to be determined whether ketamine administration can effectively prevent suicidal behaviors.

Sublingual buprenorphine/naloxone treatment is not affected by OPRM1 A118G and BDNF Va66Met polymorphisms, but alters the plasma beta-endorphin and BDNF levels in individuals with opioid use disorder

The study aimed to examine the genetic contribution to buprenorphine (BUP) treatment in individuals with opioid use disorder (OUD), with a specific focus on BDNF and OPRM1 genes. A total of 113 controls and 111 OUD patients receiving sublingual BUP/naloxone were enrolled. OPRM1 A118G and BDNF Val66Met polymorphisms were investigated by PCR-FRLP. Plasma BDNF and beta-endorphin levels were assessed by ELISA kits in both groups. Blood BUP levels were measured by LC-MS/MS and normalized with daily BUP dose (BUP/D). OPRM1 A118G and BDNF Val66Met polymorphisms didn’t have an effect on plasma beta-endorphin and BDNF levels in OUD patients, respectively. Interestingly, OUD patients had significantly higher plasma BDNF and lower beta-endorphin levels compared to the controls (p < 0.001). A negative and significant correlation between plasma BUP/D and BDNF levels was found. Age onset of first use was associated with OPRM1 A118G polymorphism. The findings indicated that sublingual BUP/naloxone may increase plasma BDNF levels, but may decrease beta-endorphin levels in individuals with OUD. Plasma BDNF level seemed to be decreased in a BUP/D concentration-dependent manner.

Association between plasma levels of BDNF and GDNF and the diagnosis, treatment response in first-episode MDD

IntroductionThe aims of our study are: i) to explore whether plasma levels of BDNF/GDNF are valuable in the diagnosis of first-episode depression; ii) to discuss whether there is an association between peripheral plasma levels of BDNF/GDNF and patients' depression severity and cognitive dysfunction; iii) to explore the association between plasma levels of BDNF/GDNF and the effectiveness of antidepressant treatment. MethodsNinety patients with first-episode unmedicated MDD and healthy controls were recruited. MDD patients were treated with antidepressant medication for 8 weeks. Patients were assessed for clinical symptoms using HDRS-17 and HAMA-14. Social and neurocognitive functioning of all subjects was assessed at baseline using the Functional Assessment Test Short Form (FAST) and the MATRICS Consensus Cognitive Battery (MCCB). At the same time, peripheral venous blood was drawn from all subjects for BDNF/GDNF peripheral plasma level analysis at baseline and after 8 weeks of treatment. ResultsThe baseline BDNF/GDNF levels in MDD patients were significantly lower than that in healthy controls. The area under ROC curve (AUC) of baseline plasma BDNF and GDNF levels predicting MDD was 0.776 (95 % CI: 0.705–0.846, p < 0.001) and 0.864 (95 % CI: 0.808–0.920, p < 0.001), respectively. The baseline GDNF level (beta = 0.425, p = 0.001), the autonomy score of FAST (beta = −0.247, p = 0.037) and BACS-SC score of MCCB (beta = 0.323, p = 0.039) were predictors of HDRS-17 reduction rate after 8 weeks' antidepressant treatment. LimitationsA longer follow-up period than 8 weeks may make the results more convincing, and the sample size of this study is still insufficient. ConclusionThe decreased plasma levels of BDNF and GDNF are strong indicators for predicting the occurrence of MDD. This preliminary finding highlighted the value of GDNF plasma concentrations in the diagnosis of MDD and the prognosis of antidepressant treatment.

A view of response and resistance to atomoxetine treatment in children with ADHD: effects of CYP2C19 polymorphisms and BDNF levels.

Although several genes have previously been studied about the treatment of Attention Deficit Hyperactivity Disorder (ADHD), the number of studies investigating the effects of genes on atomoxetine (ATX) treatment is very limited. In this study, we aimed to investigate the effect of CYP2C19 polymorphisms, which have a role in ATX biotransformation, on the treatment response and also to assess whether there is a relationship between BDNF and treatment response in children and adolescents with ADHD. One hundred children with ADHD and 100 healthy controls (HCs) were included in this study. The treatment response was assessed 2months after the start of the ATX treatment. DNA samples from peripheral venous blood were replicated using PCR and analyzed using the ILLUMINA next-generation sequencing method. The resulting fastqs were analyzed using Basespace's Variant Interpreter Program. Plasma BDNF levels were evaluated with ELISA kits. Treatment response was found to be lower in both heterozygous and homozygous carriers of the c.681G > A (CYP2C19*2) polymorphism. When the BDNF level was compared, it was found to be significantly higher in the ADHD group compared to HCs. Also, BDNF has a stronger predictive value for assessing resistance to ATX treatment. To our knowledge, this is the first study to assess the effects of CYP2C19 polymorphisms and BDNF levels together on ATX treatment in children. Further studies with an extensive population are needed to better understand the effects of CYP2C19 polymorphisms on treatment and side effects, as well as the effects of BDNF levels.

BDNF-Met polymorphism and amyloid-beta in relation to cognitive decline in cognitively normal elderly: the SCIENCe project

Brain-derived neurotrophic factor (BNDF) plays a role in synapse integrity. We investigated in 398 cognitively normal adults (60±8years, 41% female, MMSE=28±1) the joint association of the Val66Met polymorphism of the BDNF gene (Met+/-) and plasma BDNF levels and abnormal cerebrospinal fluid (CSF) amyloid-beta status (A+/-) with cognitive decline and dementia risk. Age-, sex- and education-adjusted linear mixed models showed that compared to Met-A-, Met+A+ showed steeper decline on tests of global cognition, memory, language, attention and executive functioning, while Met-A+ showed steeper decline on a smaller number of tests. There were no associations between Met+A- and cognitive decline. Cox models showed that compared to Met-A-, Met+A+ participants were at increased risk of dementia (HR=8.8, 95%CI: 2.8–27.9), as were Met-A+ participants (HR=6.5, 95%CI: 2.2–19.5). Lower plasma BDNF was associated with an increased risk of progression to dementia in the A+ participants. Our results imply that Met-carriage on top of amyloid-beta pathology might increase rate of cognitive decline to dementia.

Plasma BDNF and insight in OCD: a promising path for future research.

Plasma BDNF and insight in OCD: a promising path for future research.

Gestational acrylamide exposure and biomarkers of fetal growth: Probing the mechanism underlying the association between acrylamide and reduced fetal growth

IntroductionFour epidemiological studies have shown a negative association between prenatal acrylamide exposure and birth size. In order to shed light on the possible underlying mechanism(s), we analysed associations between acrylamide biomarkers and biomarkers related to fetal growth. MethodsIn newborns of the ENVIRONAGE birth cohort (n ranges from 215 to 434), we investigated the association between prenatal acrylamide exposure (acrylamide and glycidamide hemoglobin adduct levels in cord blood) and thyroid hormones (TSH, T3, T4 and the ratio of T4 to T3 in cord plasma), insulin-related factors (cord plasma insulin and IGF1, and placental IGF2), neurotrophins (cord plasma BDNF, and placental NGF, NT3 and NT4), and cord plasma homocysteine and progesterone, using multiple linear regression analysis. In addition, we investigated whether the biomarkers mediated the associations between prenatal acrylamide exposure and birth outcomes. ResultsWe observed lower cord plasma TSH (−10.2% [95% CI: −15.0, −4.3]) and higher placental NGF levels (10.0% [95% CI 3.7, 17.4]) for a twofold increase of acrylamide adducts, a decrease in the ratio of cord plasma free T4 and free T3 with higher acrylamide and glycidamide adducts of −2.9% (95% CI: −5.7, −0.1) and −3.9% (95% CI: −6.2, −1.6) for a twofold increase in acrylamide and glycidamide adduct levels, respectively, and higher cord plasma free T3 with increases in both acrylamide and glycidamide adducts of 2.8% (95% CI: 0.2, 5.6) and 3.6% (95% CI: 0.8, 6.6) for a twofold increase in acrylamide and glycidamide adduct levels, respectively. Additionally, a twofold increase in glycidamide adducts was associated with lower cord plasma insulin levels, particularly among newborns of non-smoking mothers (−11.2% [95% CI: −19.5, −0.1]).Cord plasma insulin seemed to mediate the association between glycidamide adducts and birth weight. ConclusionsA decrease in cord plasma insulin levels may be (a marker of) a mechanism by which gestational acrylamide exposure is associated with decreased fetal growth. The possible health consequences of the associations between gestational acrylamide exposure and thyroid hormones and neurotrophins warrant future study.

Resolvin D1 Decreases Severity of Streptozotocin-Induced Type 1 Diabetes Mellitus by Enhancing BDNF Levels, Reducing Oxidative Stress, and Suppressing Inflammation.

Type 1 diabetes mellitus is an autoimmune disease characterized by increased production of pro-inflammatory cytokines secreted by infiltrating macrophages and T cells that destroy pancreatic β cells in a free radical-dependent manner that causes decrease or absence of insulin secretion and consequent hyperglycemia. Hence, suppression of pro-inflammatory cytokines and oxidative stress may ameliorate or decrease the severity of diabetes mellitus. To investigate the effect and mechanism(s) of action of RVD1, an anti-inflammatory metabolite derived from docosahexaenoic acid (DHA), on STZ-induced type 1 DM in male Wistar rats, type 1 diabetes was induced by single intraperitoneal (i.p) streptozotocin (STZ-65 mg/kg) injection. RVD1 (60 ng/mL, given intraperitoneally) was administered from day 1 along with STZ for five consecutive days. Plasma glucose, IL-6, TNF-α, BDNF (brain-derived neurotrophic factor that has anti-diabetic actions), LXA4 (lipoxin A4), and RVD1 levels and BDNF concentrations in the pancreas, liver, and brain tissues were measured. Apoptotic (Bcl2/Bax), inflammatory (COX-1/COX-2/Nf-κb/iNOS/PPAR-γ) genes and downstream insulin signaling proteins (Gsk-3β/Foxo1) were measured in the pancreatic tissue along with concentrations of various antioxidants and lipid peroxides. RVD1 decreased severity of STZ-induced type 1 DM by restoring altered plasma levels of TNF-α, IL-6, and BDNF (p < 0.001); expression of pancreatic COX-1/COX-2/PPAR-γ genes and downstream insulin signaling proteins (Gsk-3β/Foxo1) and the concentrations of antioxidants and lipid peroxides to near normal. RVD1 treatment restored expression of Bcl2/Pdx genes, plasma LXA4 (p < 0.001) and RVD1 levels and increased brain, pancreatic, intestine, and liver BDNF levels to near normal. The results of the present study suggest that RVD1 can prevent STZ-induced type 1 diabetes by its anti-apoptotic, anti-inflammatory, and antioxidant actions and by activating the Pdx gene that is needed for pancreatic β cell proliferation.

Role of Brain Derived Neurotrophic Factor and Swimming Exercise in Cardiac Autonomic Neuropathy in Type 2 Diabetes Rat Model

Cardiac Autonomic Neuropathy (CAN) is a major chronic complications of DMII. Clinical investigations have revealed that uncontrolled DM II is frequently associated with lower levels of BDNF. This study assessed whether diminished BDNF level is the reason of CAN caused by DM II and if swimming aerobic exercise can increase BDNF level to ameliorate that CAN . Sixty rats were divided into six groups. Group I; Normal (N), Group 2; BDNF blocker, Group 3; DM II, Group 4; DM II + BDNF, Group 5; DM II + Swimming exercise and Group 6; DM II + Swimming exercise + BDNF blocker. Induction of DM II was done by intraperitoneal injection of 180 mg/kg of Nicotinamide 30 minutes before injection of 50 mg/kg Streptstozin. Swimming exercise began with a 1-week adaptation with gradual increase of swimming duration until reaching 1h swimming/day at the end of the 1st week. Then, a 7-weeks training program with 5 days/week swimming was followed. The duration of the experiment was 8 weeks during which the following parameters were measured: body weight, random blood glucose “RBG” level, plasma insulin level, heart rate “HR”, systolic blood pressure “SBP”, heart rate variability “HRV”, baroreflex sensitivity “BRS”, vascular sympathetic tone “VST” and plasma BDNF. Results revealed that BDNF significantly improved RBG level, HRV, VMT and BRS. Swimming exercise significantly increases plasma BDNF level and also improved CAN. Conclusively, BDNF can be used as a treatment regimen for CAN. Also swimming exercise has great therapeutic effect on CAN maybe by producing BDNF.