Neurotrophic Factor Concentrations Research Articles

Effects of two different early socialization models on social behavior and physiology of suckling piglets

Early socialization not only facilitates positive behaviors and cognition abilities of post-weaning piglets, but also has effects on social behavior and physiology of suckling piglets during the lactation. Therefore, this study aimed to investigate the effects of early socialization environment on social behavior, stress coping and weaning weight of suckling piglets. We selected 199 piglets (Large White×Duroc×Min pig) from 18 litters and three treatments were differentiated: intermittent contact group (IC, 6 litters), piglets of two neighboring litters were socialized twice a week for 3 h from D14 (14 days of age) to D35; continuous contact group (CC, 6 litters), piglets of two neighboring litters were socialized continuously from D14 to D35; the control group (CON, 6 litters), piglets were not socialized during the lactation. Behavioral observation occurred on D14, D15, D21, D22, D28, D29, D33 and D34, and blood samples were collected on D16, D28 and D34. The results revealed that the amount of fighting and head knocking in IC group was higher than CC and CON groups (P < 0.05). On the social interaction during the lactation, for performing piglet, piglets in CC group showed more oral-nasal contact than IC in 3 weeks of age (W3, D21 and D22) (P = 0.045), and socialized groups (CC, IC) showed more oral-nasal contact than CON in W4 (P = 0.001). The amount of mounting in CC was higher than IC and CON from W3 to W5 (P < 0.001). For receiving pig, amounts of avoiding behavior in IC and CC were higher than CON in W4 (P = 0.047). The return approach (positive response to the performing pig) of IC and CC were higher than C in W2, CC was higher than IC and CON in W3 (P = 0.003), socialized groups were higher than CON in W4 and W5 (P < 0.001). Serum epinephrine concentration in IC and CC were lower than CON on D16 (P < 0.001). The brain-derived neurotrophic factor (BDNF) concentration of IC was higher than CC and CON (P < 0.05) on D16 and D28, IC and CC were higher than CON (P = 0.004) on D34. There was no significant difference in weaning weight and cross-sucking frequency among treatments. In conclusion, the early socialization environment provided opportunities for piglets to improve their social skills, increased the expression of social behaviors and had a positive impact on the expression of BDNF in piglets.

Effects of an Oroxylum indicum Extract (Sabroxy®) on Cognitive Function in Adults With Self-reported Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Study.

Background: Oroxylum indicum has been used in traditional Ayurvedic medicine for the prevention and treatment of several diseases and may have neuroprotective effects.Purpose: Examine the effects of Oroxylum indicum on cognitive function in older adults with self-reported cognitive complaints.Study Design: Two-arm, parallel-group, 12-week, randomized, double-blind, placebo-controlled trial.Methods: Eighty-two volunteers received either 500 mg, twice daily of a standardized Oroxylum indicum extract or placebo. Outcome measures included several computer-based cognitive tasks, the Control, Autonomy, Self-Realization, and Pleasure scale (CASP-19), Cognitive Failures Questionnaire (CFQ), and the Montreal Cognitive Assessment (MoCA). Changes in the concentration of brain-derived neurotrophic factor (BDNF) were also examined.Results: Compared to the placebo, Oroxylum indicum was associated with greater improvements in episodic memory, and on several computer-based cognitive tasks such as immediate word recall and numeric working memory, and a faster rate of learning on the location learning task. However, there were no other significant differences in performance on the other assessed cognitive tests, the MoCA total score, or other self-report questionnaires. BDNF concentrations increased significantly in both groups, with no statistically-significant between-group differences. Oroxylum indicum was well tolerated except for an increased tendency for mild digestive complaints and headaches.Conclusion: The results of this first human trial on the cognitive-enhancing effects of Oroxylum indicum suggest that it is a promising herbal candidate for the improvement of cognitive function in older adults with self-reported cognitive complaints.

ELISA-based quantification of neurotrophic growth factors in urine from prostate cancer patients.

Non‐invasive procedures are needed for prostate cancer management, and urine represents a potential source of new biomarkers with translational value. Recent evidence has shown that the growth of new nerves in the tumor microenvironment is essential to prostate cancer progression. Neurotrophic growth factors are expressed by prostate cancer cells and contribute to prostate tumor innervation, but their presence in urine is unclear. In the present study, we have assayed the concentration of neurotrophic factors in the urine of prostate cancer patients. Urine was collected from a prospective cohort of 45 men with prostate cancer versus 30 men without cancer and enzyme‐linked immunosorbent assay was used to quantify nerve growth factor (NGF) and its precursor proNGF, brain‐derived neurotrophic factor (BDNF) and proBDNF, neurotrophin‐3, neurotrophin‐4/5, and glia‐derived neurotrophic growth factor. The results show that neurotrophic factors are detectable in various concentrations in both cancer and healthy urine, but no significant difference was found. Also, no association was observed between neurotrophic factor concentrations and prostate cancer grade. This study is the first quantification of neurotrophins in urine, and although no significant differences were observed between prostate cancer patients versus those without prostate cancer, or between prostate cancers of various grades, the potential value of neurotrophins for prostate cancer diagnosis and prognosis warrants further investigations in larger patient cohorts.

Resistance Or Endurance Training Increases Brain-derived Neurotrophic Factor Concentrations In Middle Age Females

Evidence continues to develop regarding the positive connection between chronic physical activity and brain health. Brain derived neurotropic factor (BDNF) works collaboratively with other growth factors to encourage exercise-induced enhancements in cognitive function, neuronal growth, learning, memory, and overall brain health. However, the optimal stimulus and processes by which BDNF is enhanced has not yet been firmly established. PURPOSE: To compare the effects of 16 weeks aerobic (AT) or resistance training (RT) on mRNA concentrations in monocytes and basal plasma BDNF in sedentary middle-aged females. METHODS: Twenty-six untrained overweight female participants (age: 51.1 ± 4.2 years, weight: 69 ± 5.4 kg and BMI: 27.1 ± 2.1 kg/m2) were randomly assigned to AT, RT, or control (C) groups. Blood samples and body composition were collected at baseline and 48-h after the last training session. Participants in the AT and RT groups exercised three times a week for 16-weeks under the supervision of exercise specialists. RESULTS: There were significant group x time interactions (p < 0.05) for both plasma and mRNA concentrations of BDNF which significantly increased in both AT (plasma: 423 ± 13 pg/ml, p < 0.001; mRNA: 1.9 ± 2.9, p < 0.044) and RT (plasma: 610 ± 22.3 pg/ml, p < 0.001; mRNA: 0.6 ± 0.7, p < 0.039) when compared to C. There was also a significant group x time interaction (p < 0.05) for body fat percentage, which was significantly decreased in both AT (-1.8 ± 0.8 %, p < 0.001) and RT (-1.2 ± 1.5 %, p < 0.043) compared to the control group There were no significant differences between AT- and RT-induced improvements. There was a significant correlation between changes in plasma concentrations of BDNF and monocyte mRNA of BDNF (r = 0.506; p < 0.05). CONCLUSIONS: Sixteen weeks of chronic AT or RT increased basal BDNF monocyte mRNA, a key moderator of brain health, expression and plasma concentrations in sedentary middle-aged females. Future research is important to examine the effects of different exercise intensities, durations, frequencies, and exercise types on plasma BDNF concentrations.

Decreased Serum Brain-Derived Neurotrophic Factor Concentrations 72 Hours Following Marathon Running.

Background: Physical exercise has been linked to beneficial effects on brain plasticity. One potential key mechanism for this relationship is an exercise-induced increase of brain-derived neurotrophic factor (BDNF). However, the kinetics of BDNF in athletes during training phase, extreme exercise competition, and recovery period have not been investigated so far.Methods: We assessed serum BDNF concentrations in 51 marathon runners (23% female, mean age 43 years) in a longitudinal study design over a period of 6 months. Assessments were conducted during the training period before the marathon and after the marathon race during short-term (24 to 72 h) and long-term (3 months) follow-ups. Potential confounders (fitness level, sex, and platelet count) were included in subsequent linear-model analyses.Results: Linear mixed-model analyses revealed a main effect of time for BDNF concentrations over the study period (F(4,89.389) = 4.296, p = 0.003). Values decreased significantly with the lowest values at 72 h after the marathon compared to baseline (p = 0.025), a finding that was more pronounced in the larger male cohort.Conclusion: Prolonged exercise induces a significant decrease in serum BDNF concentration 72 h post-exercise. We assume that this observation is mainly driven by regenerative mechanisms and a higher muscular utilization.

A methodology for an acute exercise clinical trial called dementia risk and dynamic response to exercise

Exercise likely has numerous benefits for brain and cognition. However, those benefits and their causes remain imprecisely defined. If the brain does benefit from exercise it does so primarily through cumulative brief, “acute” exposures over a lifetime. The Dementia Risk and Dynamic Response to Exercise (DYNAMIC) clinical trial seeks to characterize the acute exercise response in cerebral perfusion, and circulating neurotrophic factors in older adults with and without the apolipoprotein e4 genotype (APOE4), the strongest genetic predictor of sporadic, late onset Alzheimer’s disease. DYNAMIC will enroll 60 older adults into a single moderate intensity bout of exercise intervention, measuring pre- and post-exercise cerebral blood flow (CBF) using arterial spin labeling, and neurotrophic factors. We expect that APOE4 carriers will have poor CBF regulation, i.e. slower return to baseline perfusion after exercise, and will demonstrate blunted neurotrophic response to exercise, with concentrations of neurotrophic factors positively correlating with CBF regulation. Preliminary findings on 7 older adults and 9 younger adults demonstrate that the experimental method can capture CBF and neurotrophic response over a time course. This methodology will provide important insight into acute exercise response and potential directions for clinical trial outcomes.ClinicalTrials.gov NCT04009629, Registered 05/07/2019.

Kinetics of serum brain-derived neurotrophic factor (BDNF) concentration levels in epileptic patients after generalized tonic-clonic seizures

ObjectiveEpilepsy is a chronic neurological disorder characterized by the periodic and unpredictable occurrence of seizures. The serum level of brain-derived neurotrophic factor (BDNF) has been suggested to be a potential biomarker that could detect differences in epilepsy patients. Although there is considerable neurobiological evidence linking BDNF to epilepsy, only a small number of studies investigated the relationship between BDNF serum levels and epilepsy, and these studies obtained inconsistent results. The aim of this study was to elucidate BDNF serum levels in epilepsy cases. MethodsCollectively, group of 143 patients (n = 143) were included in this study and subsequently divided into two groups consisting of individuals after singular generalized tonic-clonic seizures (n = 50) and patients with chronic epilepsy (n = 93). The samples from patients with acute epilepsy were collected 1−3 hours and 72 h after seizure, and a single collection was performed from patients with chronic epilepsy. These samples were compared to the control group (n = 48) using ELISA. ResultsIn the present study, we observed a significant decrease of BDNF serum levels in patients after generalized tonic-clonic seizures compared to the control group. Furthermore, the observed decrease of BDNF levels in this group was sustained at 1 and 72 h after seizure insult. We did not show the relationship between BDNF levels and age, etiology of epilepsy and the duration of illness. SignificanceOur results and the findings of previous studies indicate that the serum BDNF level significantly decreases after seizures and should be considered when measuring BDNF in patients with chronic epilepsy. It might be also influenced by neurodegenerative processes, which may be involved in the etiopathogenesis of particular epilepsy syndromes.

Neurotrophic Factors in Human Milk in Early Lactation and the Effect of Holder and Microwave Pasteurization on Their Concentrations.

The objective of this study was to determine the level of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in human milk in the first 2 weeks of breast-feeding and compare the effects of Holder pasteurization (HoP, 62.5 °C, 30 minutes) and microwave pasteurization (MP) at constant temperature (62.5 °C) on the concentraion of both neurotrophic factors (NFs). Concentration of NFs in human milk was determined using a commercially available ELISA assay. The average concentration of BDNF and GDNF in milk was 11 ± 6 ng/mL and 336 ± 238 pg/mL, respectively. There was a positive correlation between the concentrations of BDNF and GDNF in human milk and day of lactation (r = 0.441, P < 0.05 and r = 0.482, P < 0.05, respectively). In addition, there was a significant correlation between the levels of BDNF and GDNF (r = 0.366, P < 0.05). HoP and MP for 10 minutes affected both NF levels similarly, causing degradation of BDNF by about 24% and 17%, and GDNF by 47% and 45%, respectively. Use of MP for 5 minutes resulted in preservation of nearly 91% BDNF and 79% GDNF in human milk. In the pasteurization processes carried out, results showed that GDNF is more susceptible to degradation under the influence of high temperature. To the authors' best knowledge, this is the first study evaluating the effects of HoP and MP at constant temperature on the concentration of NFs in human milk. It was found that the MP for 5 minutes is the optimal method.

Acute caffeine intake in humans reduces post exercise performance in learning and memory.

To clarify the acute effect of caffeine on postexercise memory and learning performance. Eight male slow-to-normal caffeine metabolizers, unhabituated to caffeine, were recruited into this randomized, double blind, placebo controlled, cross over study. Caffeine (150mg) or the placebo was consumed one hour prior to two 30min submaximal cycling sessions. Blood was collected at the beginning, after 20 and 35min of exercise and 30min postexercise. Mature brain-derived neurotrophic factor (BDNF) and proBDNF concentrations were determined. Auditory memory was assessed immediately, 30min and 24h postexercise. Participants averaged lower scores in every measure of learning and memory after ingesting caffeine compared to the placebo. Although the mean did not differ significantly for all measures, significant differences were found between the caffeine and placebo groups for the three indices; learning over time, short-term index and retroactive interference. The ratio of serum mBDNF:proBDNF increased with exercise across all time points. No significant difference in the mBDNF:proBDNF ratio was observed between treatment groups. The consumption of caffeine prior to exercise may impair an unhabituated individual's capacity to learn and recall auditory information postexercise. However it is yet to be elucidated whether this is through caffeine's modulating effects on brain BDNF.

Effects of Positive Human Contact during Gestation on the Behaviour, Physiology and Reproductive Performance of Sows.

Simple SummaryStress can compromise animal welfare and impact the productivity of farm animals. In intensive production systems where close interactions between stockpeople and animals occur regularly, human contact of a positive nature may facilitate stress resilience. This experiment studied the effects of human interaction on stress in pigs, by providing sows in their home pens with either regular positive handling by stockpeople or routine human contact. Stress resilience was studied by assessing the behaviour, physiology and productivity of pigs in these two treatments. Positive human contact was effective at reducing the fear responses of sows towards stockpeople conducting routine husbandry practices in the home pens. However, the positive handling treatment did not affect the behaviour of pigs towards other stressors imposed outside of the home pen, acute or basal physiological measures of stress or reproductive performance. Sows receiving positive handling showed reduced physical interaction with the stockpeople delivering the treatment over time, which may indicate habituation to the novel or possible rewarding elements of the human contact treatment. This work confirms that regular positive interaction with stockpeople does reduce the fear of sows to stockpeople, but does not always confer stress resilence.Previous positive interactions with humans may ameliorate the stress response of farm animals to aversive routine practices such as painful or stressful procedures, particularly those associated with stockpeople. We studied the effects of positive handling by providing younger (parity 1–2) and older (parity 3–8) sows housed in pens of fifteen (n = 24 pens in total) with either positive human contact (+HC) or routine human contact (control) during gestation. The +HC treatment involved a familiar stockperson patting and scratching sows and was imposed at a pen-level for 2 min daily. Measurements studied included behavioural, physiological and productivity variables. The +HC sows showed reduced avoidance of the stockperson conducting pregnancy testing and vaccination in the home pens, however the behavioural and cortisol responses of sows in a standard unfamiliar human approach test did not differ. There were no effects of +HC on aggression between sows, serum cortisol or serum brain-derived neurotrophic factor concentrations during gestation, or on the behavioural and cortisol response to being moved to farrowing crates. There were also no effects of +HC on the maternal responsiveness of sows, farrowing rate or the number of piglets born alive, stillborn or weaned. Sows in the +HC pens reduced their physical interaction with the stockpeople imposing the treatment after 2 weeks, which suggests the sows may have habituated to the novel or possible rewarding elements of the handling treatment. This experiment shows that regular positive interaction with stockpeople does reduce sows’ fear of stockpeople, but does not always confer stress resilence.

The effects of endurance exercise combined with high-temperature head-out water immersion on serum concentration of brain-derived neurotrophic factor in healthy young men

Objectives To evaluate acute changes in serum brain-derived neurotrophic factor (BDNF) concentration following combined endurance exercise and heat stress through head-out water immersion (HOI). Setting Observational study with crossover design. Methods Ten healthy young male participants performed HOI at 40 °C (40 °C HOI) or continuous cycling at 60% of maximal oxygen uptake while immersed in 40 °C (40 °C HOI-ex) or 23 °C water (23 °C HOI-ex) for 15 min. Serum BDNF, cortisol and lactate concentrations, and core temperature (Tcore) were measured pre, immediately post, and 15 and 30 min post-immersion. Results BDNF concentration increased immediately and 15 min after 40 °C HOI-ex, but not after 40 °C or 23 °C HOI-ex. No changes in Tcore concentration were observed during 23 °C HOI-ex (Pre; 37.3 °C ± 0.3 °C, Post; 37.8 °C ± 0.2 °C, Post 15; 37.4 °C ± 0.3 °C, Post 30; 37.2 °C ± 0.2 °C). Tcore increased significantly post, post 15, and post 30 min of 40 °C HOI (Pre; 37.1 °C ± 0.4 °C, Post; 38.8 °C ± 0.5 °C, Post 15; 37.9 °C ± 0.4 °C, Post 30; 37.9 °C ± 0.2 °C) and 40 °C HOI-ex (Pre; 37.2 °C ± 0.2 °C, Post; 40.2 °C ± 0.7 °C, Post 15; 38.9 °C ± 0.5 °C, Post 30; 38.3 °C ± 0.5 °C). Tcore was higher in 40 °C HOI-ex compared with 40 °C HOI and 23 °C HOI-ex immediately post and post 15 min. Plasma lactate and cortisol were significantly higher in 40 °C HOI-ex compared with 40 °C HOI and 23 °C HOI-ex after immersion (p = 0.001). Conclusion While 15 min HOI alone or thermoneutral exercise do not increase BDNF concentration, both combined may form a time-efficient strategy to acutely elevate BDNF.

New perspectives of immunomodulation and neuroprotection in glaucoma.

Glaucoma is the neurodegenerative disease of retinal ganglion cells. The main risk factor for glaucoma is increased intraocular pressure. The processes leading to cell death due to presence of the injury factor comprise multiple molecular mechanisms, as well as the immunological response. The knowledge of immunological mechanisms occurring in glaucomatous degeneration makes it possible to introduce glaucoma treatment modulating the cellular degradation. The glaucoma treatment of the future will make it possible not only to lower the intraocular pressure, but also to moderate the intracellular mechanisms in order to prevent retinal cell degeneration. Citicoline is a drug modulating glutamate excitotoxicity that is already in use. Rho kinase inhibitors were found to stimulate neurite growth and axon regeneration apart from lowering intraocular pressure. The complementary action of brimonidine is to increase neurotrophic factor (NTF) concentrations and inhibit glutamate toxicity. Immunomodulatory therapies with antibodies and gene therapies show promising effects in the current studies. The supplementation of NTFs prevents glaucomatous damage. Resveratrol and other antioxidants inhibit reactive oxygen species formation. Cell transplantation of stem cells, Schwann cells and nerve extracts was reported to be successful so far. Our review presents the most promising new strategies of neuroprotection and immunomodulation in glaucoma.

Impact of mesenchymal stem cells derived conditioned media on neural progenitor cells

Neurodegenerative diseases are common problem for companion animals. Due to the limited ability of injured axons to regenerate, innovative therapies combined with rehabilitation have been applied and evaluated. Among them, stem cells and their conditioned media implantation, which can ameliorate damaged tissue has been suggested as a promising treatment strategy. The main goal of our study was to characterize mesenchymal stem cells (MSC) derived from canine adipose tissue (AT-MSC) and umbilical cord (UC-MSC) and analyse effect of their conditioned media (CM) on neurite outgrowth of neural progenitor cells isolated from the brain cortex of neonatal rats. MSC from both sources showed high osteogenic and chondrogenic potential and expression of CD90 and CD29. Furthermore, both UC-MSCCM and AT-MSCCM stimulated neurite growth. Interestingly, this effect was more pronounced with UC-MSCCM when compared to AT-MSCCM in vitro, which may be related to the different content of neurotrophic factors included in the CM.

Antidepressive Therapy Has No Effect on Ciliary Neurotrophic Factor Concentration in Blood Serum of Patients with Melancholic Depression

Ciliary neurotrophic factor (CNTF) is a 22-kDa cytokine belonging to the interleukin-6 family and is mainly expressed in glial cells of the central and peripheral nervous systems...

Prospects Of Using Resveratrol For Cognitive Impairment Correction In Patients With Type II Diabetes Mellitus

Our goal was to study the effectiveness of resveratrol in correcting cognitive impairments and in normalization of neurotrophin levels in patients with type II diabetes mellitus. Material and Methods ― In a randomized placebo-controlled trial, 100 patients with a verified diagnosis of type II diabetes mellitus took part, who were subsequently placed into two groups: the treatment group of 50 patients taking a polyphenol therapeutic drug in addition to standard therapy, and the comparison group of 50 indivuduals taking a placebo medication in addition to standard therapy. The control group consisted of 30 individuals belonging to the health group I sensu RF Ministry of Healthcare. Treatment efficacy was assessed using the Montreal Cognitive Assessment (MoCA) scale. The concentrations of insulin-like growth factor 1 (IFR-1), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) in blood plasma were analyzed before and after treatment completion (10 weeks later). Results ― Before starting treatment, patients exhibited an increase in the level of IFR-1 and a decrease in the content of neurotrophic factors (BDNF and NGF) in their blood plasma. In patients receiving resveratrol in addition to standard treatment, changes in IFR-1, BDNF and NGF in blood plasma were more noticeable relative to the comparison group and approached the values of the control group. According to the MoCA scale, more pronounced dynamics of cognitive functions was observed in patients of the treatment group. Conclusion ― The high efficiency of the polyphenol therapeutic drug resveratrol in the correction of cognitive impairments in patients with type II diabetes mellitus was established. The use of resveratrol promoted the normalization of the levels of IFR-1 and neurotrophic factors in the blood plasma: in the treatment group, a more pronounced statistically significant decrease in the concentration of IFR-1, along with an increase in BDNF and NGF levels, were observed relative to the control group. The clinically significant effect of resveratrol was in the reduction of cognitive deficit symptoms, which was confirmed by the data of dynamic monitoring on the MoCA scale: in treatment group, there was a statistically significant improvements of optical and spatial functions, attention, abstract thinking, and fulfilling delayed reproduction task; in the comparison group, there was a statistically significant improvement solely of completing delayed reproduction task.

P.355 Delayed increase of perinatally downregulated serum brain-derived neurotrophic factor concentrations may be a risk factor of postpartum depression

To determine the extent to which human rights considerations influence the attitudes of healthcare providers in Brazil with regard to access to the human papillomavirus (HPV) vaccine for females over 13 and males of all ages.From May to August 2015, we conducted a cross-sectional study among healthcare providers in eight public health clinics in the city of Mauá, Brazil. Frequency analysis was conducted across three subject areas: access, knowledge, and attitudes.A total of 154 surveys were analyzed. Providers reported their perception that Brazilians do not have equal access to health (80%) and the vaccine exclusions limit an individual's right to health (72%). Providers stated it is medically effective to vaccinate females over the age of 13 (77%), these females should be vaccinated (84%), and they would vaccinate them (82%). Similar responses were reported for males.Cervical cancer is the 4th leading cause of cancer among females in Brazil. Most cervical cancer cases are caused by persistent HPV infection, preventable through HPV vaccination. Limiting access to the HPV vaccine when medically efficacious is a perceived infringement of an individual's right to health. Brazil has a constitutional responsibility to reduce these access barriers.

Effects of High White and Brown Sugar Consumption on Serum Level of Brain-Derived Neurotrophic Factor, Insulin Resistance, and Body Weight in Albino Rats.

BackgroundIn recent decades, consumption of simple sugars has increased dramatically, which contributes to health problems including insulin resistance and obesity. In this study, we investigated the effects of high concentrations of white sugar (WS) and brown sugar (BS) on serum concentration of brain-derived neurotrophic factor (BDNF), insulin resistance, and body weight in albino rats.MethodsTwenty-four male Wistar rats were randomly divided into three groups: control, a group treated with 15% WS, and a group treated with 15% BS. Rats were given WS and BS by gavage (daily) for 42 days. At the end of the intervention period, serum level of BDNF, insulin resistance, and body weight were measured.ResultsBody weight and insulin resistance were significantly increased and serum BDNF level was decreased in both WS and BS groups compared to the control group (P<0.05). In the WS-treated rats, the amount of changes in the insulin resistance, body weight, and serum BDNF level was greater compared to that in BS-treated (P<0.05).ConclusionDue to the adverse effects of consuming high levels of WS and BS on serum level of BDNF, insulin resistance, and body weight, high intakes of these sweeteners are not recommended.

Plasma Brain-Derived Neurotrophic Factor (BDNF) Concentration and BDNF/TrkB Gene Polymorphisms in Croatian Adults with Asthma.

Brain-derived neurotrophic factor (BDNF) and its tropomyosin-related kinase B (TrkB) receptor might contribute to normal lung functioning and immune responses; however, their role in asthma remains unclear. Plasma BDNF concentrations, as well as BDNF and NTRK2 (TrkB gene) polymorphisms, were investigated in 120 asthma patients and 120 healthy individuals using enzyme-linked immunosorbent assay and polymerase chain reaction, respectively. The genotype and allele frequencies of BDNF Val66Met (rs6265) and NTRK2 rs1439050 polymorphisms did not differ between healthy individuals and asthma patients, nor between patients grouped according to severity or different asthma phenotypes. Although plasma BDNF concentrations were higher among healthy subjects carrying the BDNF Val66Met GG genotype compared to the A allele carriers, such differences were not detected in asthma patients, suggesting the influences of other factors. Plasma BDNF concentration was not affected by NTRK2 rs1439050 polymorphism. Asthma patients had higher plasma BDNF concentrations than control subjects; however, no differences were found between patients subdivided according to asthma severity, or Type-2, allergic, and eosinophilic asthma. Higher plasma BDNF levels were observed in asthma patients with aspirin sensitivity and aspirin-exacerbated respiratory disease. These results suggest that plasma BDNF may serve as a potential peripheral biomarker for asthma, particularly asthma with aspirin sensitivity.

Sex‐specific behavioral and neurogenic responses to cocaine in mice lacking and blocking dopamine D1 or dopamine D2 receptors

Adult neurogenesis in rodents is modulated by dopaminergic signaling and inhibited by cocaine. However, the sex-specific role of dopamine D1 and D2 receptors (D1R, D2R) in the deleterious effect of cocaine on adult neurogenesis has not been described yet. Here, we explored sex differences in (a) cell proliferation (5'-bromo-2'-deoxyuridine [BrdU]), (b) neural precursor (nestin), (c) neuronal phenotype (BrdU/β3-tubulin), and (d) neuronal maturity (NeuN) in the subventricular zone (SVZ) of the lateral ventricles and striatum of mice with genetic deletion (D1-/- , D2-/- ) or pharmacological blockage (SCH23390: 0.1 mg/kg/day/5 days; Raclopride: 0.3 mg/kg/day/5 days) of D1R and D2R, and treated (10 mg/kg/day/5 days) and then challenged (5 mg/kg, 48 hr later) with cocaine. Results indicated that hyperactivity responses to cocaine were absent in D1-/- mice and reduced in SCH23390-treated mice. Activity responses to cocaine were reduced in D2-/- males, but absent in D2-/- females and increased in Raclopride-treated females. D1R deletion blocked the deleterious effect of cocaine on SVZ cell proliferation in males. Cocaine-exposed D1-/- males also had reduced neuronal phenotype of SVZ newborn cells and increased striatal neuronal maturity. D2-/- mice had lower proliferative and neural precursor responses. Cocaine in D2-/- females or coadministered with Raclopride in wild-type females improved SVZ cell proliferation, an effect that positively correlated with plasma brain-derived neurotrophic factor (BDNF) concentrations. In conclusion, the sex-specific D1R and D2R signaling on SVZ cell proliferation, neural progenitor and neuronal maturity is differentially perturbed by cocaine, and BDNF may be required to link D2R to neuroplasticity in cocaine addiction in females.

Biotechnological approach for substantiation of differentiated application of neuroprotective therapy in patients with hereditary neuromuscular diseases

Hereditary neuromuscular diseases are a group of genetic diseases characterized by an onset of the disease in most cases in childhood, having a steadily progressive course of the pathological process, leading to more rapid disability of patients and having a high mortality rate at the age of 18–20 years.Objective. To study a condition of the intra-organ structure in patients with hereditary muscular atrophy and muscular dystrophy using testing of nerve tissue in the organotypic environment in order to justify the prescription of symptomatic neuroprotective therapy.Materials and methods. Ninety patients with hereditary neuromuscular diseases (spinal muscular atrophy types 1, 2 and 3 [n = 30], Duchenne muscular dystrophy [n = 60]) were examined; the control group consisted of 30 healthy people. In vitro – explants of sensory ganglia of 10–12-day-old chicken embryos. A comprehensive clinical, laboratory and experimental study was conducted. Concentrations of neurotrophic factors (Brain Growth Factor, Nerve Growth Factor, Ciliary Neurotrophic Factor) were determined by the enzyme immunoassay method in blood plasma samples using RayBiotech kits and in accordance with the manufacturer's instructions. The experimental study included 300 explants of sensory ganglia of 10–12-day chicken embryos cultured in Petri dishes on collagen substrates in a CO2 incubator (Sanyo, Japan) for 3 days at 36.5 °C and 5% CO2. In order to clarify the biochemical mechanisms involved in pathological cascades in patients with hereditary neuromuscular diseases, a test system was developed that included a sequential analysis of the patient's blood plasma in an organotypic tissue culture at a dilution of 1: 70, followed by an addition of reagents to the medium: synthetic nerve growth factor (NGF) (100 pg/ml). Explant cultivation was carried out according to the method developed at Institute for Physiology n.a. I.P. Pavlov (Saint Petersburg, Russia). Visualization of the objects was made using Axiostar Plus microscope (Carl Zeiss, Germany). The resulting images were analyzed with the help of ImageJ software. A morphometric method was used to quantify the growth of explants. The area index (AI) was calculated as the ratio of the area of the explant growth zone to the initial area. AI reference value was 100%.Results. Brain Growth Factor concentration was at the highest level in patients with progressive amyotrophy, while in patients with progressive myodystrophy, the blood concentra tion of this factor was at a level comparable to the control data, and in some patients the concentration of Brain Growth Factor was lower than normal. NGF concentration showed the highest values in the group of patients with progressive amyotrophies. Blood plasma of patients with progressive amyotrophy dose dependently inhibits the growth of neurites of the spinal ganglia, and blood plasma of patients with myodystrophy has a neurite-weakening effect on the growth of neurites. Introduction of synthetic NGF (100 pg/ml) to organotypic tissue culture containing blood plasma of patients with myodystrophy increased the area index value of 114.0 [111.0; 116.0]%; in explants containing blood plasma of patients with progressive amyotrophy, increased growth of neurites was not observed AI = 80.0 [74.5; 83.0]%.Conclusion. The data obtained are indicative of features of neurotrophic regulation in patients with hereditary muscular atrophy and muscular dystrophy, which should be taken into account when conducting symptomatic treatment aimed at stimulating reparative processes in the nervous tissue. We recommend patients with the neurite-weakening effect of blood plasma to have neuroprotective drugs therapy, and in case of patients with neuritis-inhibiting effect on neurites in organotypic culture of nervous tissue we recommend choosing a drug in vitro individually using pharmacological analysis.