Neurotropic Factor Research Articles

Correlation of physical activity with cognition and mental health in medical students

Low physical activity increases the number of non-communicable diseases. This phenomenon occurs in medical students. This study aimed to determine the correlation between sedentary behavior and physical activity on cognition, mental health, cortisol, and brain derived neurotropic factor (BDNF). Using a cross-sectional design of observational study, eighty-six medical students were involved in this study. The subjects were interviewed to assess cognitive function and depression levels. Saliva was taken to measure cortisol and BDNF level. Bivariate analysis was performed using the Spearman test. Depression is the only variable that correlates significantly with habitual physical activity (p=0.025, r=-0.214). Sedentary behavior has a weak correlation with cognitive failure, anxiety, and depression ([p=0.046, r=0.216]; [p=0.039, r=0.223]; [p=0.011, r=0.273]). The results found that high physical activity improves mental health and cognition. This study suggested that physical activity can alleviate symptoms of depression and anxiety among medical students.

Post-traumatic stress disorder: Cerebral and extracerebral processing of traumatic memories and treatment strategies

Post-traumatic stress disorder (PTSD) is a severe neuropsychiatric condition characterized by anxiety-related symptoms, including intrusive memories. However, the exact anatomic location of traumatic memories remains unclear. Traumatic imagery may involve the amygdala and posterior cingulate cortex, rather than the hippocampus. Besides the central nervous system, cells and even proteins can process information and store memories. For instance, >36% of cardiac transplant recipients inherit donor personality traits, emphasizing that tissues can store and recall memories. Moreover, physical therapists mention “musculofascial memories,” that is, the ability of muscles and fascia to retain the memory of past injuries and adapt their function accordingly. Immune cells record previous infections, demonstrating the broader perspective of memory storage in the body. At the cellular level, psychological stress induces premature cellular senescence, a survival program characterized by proliferation arrest; resistance to apoptosis; and a toxic secretome known as the senescence-associated secretory phenotype (SASP). SASP contains brain-derived neurotropic factor (BDNF), a neurotrophin linked to fear memory that is frequently elevated in the peripheral blood of patients with PTSD. Endothelial cells (ECs), the tiles paving the lumen of large and small vessels, age earlier than other cells in patients with severe mental illness, including PTSD. Senescent ECs release SASP directly into the systemic circulation, spreading senescence throughout the body. In this narrative review, we hypothesize that ECs store traumatic memories and SASP-associated BDNF activates traumatic imagery. We also discuss membrane lipid replacement, mitochondrial transplantation and transfer, and several natural and synthetic compounds that may counteract endothelial senescence and SASP.

Effects of Artemisia asiatica ex on Akkermansia muciniphila dominance for modulation of Alzheimer's disease in mice.

The gut microbiome influences neurological disorders through bidirectional communication between the gut and the brain, i.e., the gut-brain axis. Artemisia asiatica ex, an extract of Artemisia asiatica Nakai (Stillen®, DA-9601) has been reported to improve depression by increasing brain-derived neurotropic factor. Therefore, we hypothesized that DA-9601 can be a potential therapeutic candidate for Alzheimer's disease (AD) acting through the gut-brain axis. Four groups of Tg2576 mice were used as the animal model for AD: wild type mice (n = 6), AD mice (n = 6), and DA-9601-administered AD mice given dosages of 30mg/kg/day (DA_30mg; n = 6) or 100mg/kg/day (DA_100mg; n = 6). Microglial activation, blood‒brain barrier integrity, amyloid beta accumulation, cognitive behavior, and changes in the gut microbiome were analyzed. DA-9601 improved the cognitive behavior of mice (DA_30mg **p<0.01; DA_100mg **p<0.01) and reduced amyloid beta accumulation (DA_30mg ***p<0.001; DA_100mg **p<0.01). Increased Iba-1 and upregulation of claudin-5 (DA_30mg *p<0.05) and occludin (DA_30mg **p<0.01; DA_100mg ***p<0.001) indicated altered microglial activation and improved blood‒brain barrier integrity. Akkermansia muciniphila was dramatically increased by DA-9601 administration (DA_30mg 47%; DA_100mg 61%). DA-9601 improved AD pathology with Akkermansia muciniphila dominance in the gut microbiome in a mouse model of AD, inferring that DA-9601 can affect AD through the gut-brain axis.

Antidepressant Herbal Plants: An Updated Review

The symptoms of this illness include mood swings, protracted melancholy, disinterest, and diminished cognitive performance. These symptoms give the patient discomfort and have a substantial negative impact on their capacity to function and lead fulfilling personal, social, and professional lives. Depression treatment has to be comprehensive and involve medicine. For several centuries, herbal chemicals have been the subject of scientific inquiry, and ongoing studies are being conducted to explore their possible medical benefits. Herbs used in traditional medicine have been shown to be highly beneficial in lowering depression and its symptoms as well as enhancing patient function. Plants are used in biology and medicine in a variety of ways. They are an excellent resource for the creation of innovative drugs due to their high levels of safety, accessibility, availability, tolerance, and low levels of toxicity. Depression is caused by a multitude of variables, such as inflammation, brain-derived neurotropic factor (BDNF), hypothalamic-pituitary-adrenal (HPA) axis, and monoamine neurotransmitters (dopamine, serotonin (5-HT), noradrenaline, and 5-HT). Herbal medicines have gained a lot of attention lately since they are less costly and have less adverse effects than traditional depression treatments. Recent years have seen a significant amount of study on the possible application of sedative and antidepressant plants. The primary emphasis of this review has been herbal medications with antidepressant properties. Keywords: Depression, herbal medications. Herb, antidepressant plants

Repurposing celecoxib as adjuvant therapy in patients with Parkinsonian disease: a new therapeutic dawn: randomized controlled pilot study.

The clinical presentations of Parkinson's disease (PD), a chronic neurodegenerative condition, include bradykinesia, hypokinesia, stiffness, resting tremor, and postural instability. Recently, neuroinflammation is involved in pathogenesis of PD. Application of nonsteroidal anti-inflammatory drugs captured attention to treat these neuroinflammation. To investigate the possible effectiveness of celecoxib in patients with PD treated with conventional treatment. Sixty outpatients who fulfilled the inclusion requirements for PD were enrolled in this randomized, prospective, and controlled study. The patients were allocated into two groups at random (n = 30); the control group received standard PD treatment, consisting of levodopa/carbidopa, and the celecoxib group received standard PD treatment plus celecoxib. A neurologist evaluated each patient at the beginning of the treatment and after 6months. Assessment of Unified Parkinson's disease rating scale (UPDRS) for each patient. Before and after treatment, α -synuclein (α-Syn), tumor necrosis factor alpha (TNF-α), Toll like receptors-4 (TLR-4), nuclear factor erythroid 2-related factor 2 (Nrf-2) and brain-derived neurotropic factor (BDNF) were assessed. Paired and unpaired t tests were used to assess statistical significance within and between groups respectively. The celecoxib group exhibited a significant and statistical reduction in the level of measured parameters by unpaired t test as followed: TLR-4 (p = 0.004), TNF-α (p = 0.042), and α-Syn (p = 0.004) apart from a significant increase in BDNF (p = 0.0005) and Nrf-2 (p = 0.004), in comparison with the control group. Also, UPDRS was significantly decreased in celecoxib group (p < 0.05). Celecoxib could be a promising adjuvant therapy in managing patients with PD. NCT05962957.

Maternal metformin administration during the pre-gestation period improves transient cerebral ischemia injury in male offspring rats

Purpose: It seems that maternal intervention, which may involve epigenetic mechanisms, can affect cerebral ischemia in offspring. Metformin consumption by the mother activates the AMP-activated protein kinase (AMPK) pathway. Metformin has also induced the AMPK and protected neurons in cerebral ischemia. This study investigates the effect of maternal metformin administration, which activates the AMPK pathway, on cerebral ischemia in offspring Methods: Animals were separated into four groups: sham, 2-vessels occlusion (2VO), Met+2VO, Met+compound c (CC)+2VO. Female rats were administrated with metformin at a dose of 200 mg.kg-1 body weight for 2 weeks prior to mating. After the final metformin injection, each female rat was paired with an intact adult male to allow for mating. Sixty-days old offspring underwent cerebral ischemia and then memory-related tests were done. Results: Current data revealed that the neurological deficits score was reduced Met+2VO group (P&lt;0.001), and the memory increased (P&lt;0.001) in comparison to the 2VO. The Bcl-2/Bax ratio declined in the metformin group (P&lt;0.001) while the Brain-Derived Neurotropic Factor (BDNF), c-fos, p-AMPK/AMPK ratio and Histone H3K9 acetylation in the hippocampus augmented significantly compared to the 2VO group (P&lt;0.001). Conclusion: These findings indicated that the metformin intervention via AMPK activation could improve the movement disability, enhance spatial memory, increase neural plasticity, and augment the bioenergetics state and histone acetylation in the hippocampus of the offspring.

Prediction of molecular targets for antidepressant potential of hydroalcoholic extract of Tamarindus indica using network pharmacology approach and evaluating its efficacy in Chronic Unpredictable Mild Stress model in mice.

The prevalence of psychological disorders has surged since the 1990s, posing a significant global health burden with depressed individuals averaging six lost hours per week and contributing to over 20% of all missed workdays. Current antidepressants, while effective for some, have limited efficacy, dietary restrictions, and adverse effects, including liver damage and hypertension. Natural remedies offer promising therapeutic potential with minimal side effects. Tamarindus indica (TI) is a plant that grows in the shape of a tree. Network pharmacology of TI revealed the key targets MAPK, D1-6, 5HT, DAT, MAO, COMT, PKA, PKC, AKT, and VMAT, which are linked to prominent key pathways such as dopaminergic and serotonergic. The cell viability assays on SH-Sy5y cells indicated a favourable safety profile with an IC50 of 573.99µg/ml and further, the in vivo efficacy was observed through Chronic Unpredictable Mild Stress (CUMS) model in mice. The hydroalcoholic extract of TI demonstrated antidepressant effects, significantly reducing immobility time in the Tail Suspension Test (TST) and Forced Swim Test (FST). Additionally, locomotor activity, assessed via the Open Field Test (OFT), was significantly increased in the treatment group compared to CUMS mice. Biochemical analyses revealed elevated Brain Derived Neurotropic Factor (BDNF), decreased cortisol levels, and reduced catechol-O-methyltransferase (COMT) concentration in TI-treated (50mg/kg) groups. These findings underscore the potential of TI as a natural antidepressant, offering a promising avenue for further therapeutic development in depression management. The current study did not evaluate the level of neurotransmitters in the brain, which will be evaluated in future studies.

Kappa Opioid Receptor Activation Induces Epigenetic Silencing of Brain-Derived Neurotropic Factor via HDAC5 in Depression.

Treatment-resistant depression (TRD) occurs in almost 50% of the depressed patients. Central kappa opioid receptor (KOR) agonism has been demonstrated to induce depression and anxiety, while KOR antagonism alleviates depression-like symptoms in rodent models and TRD in clinical studies. Previously, we have shown that sustained KOR activation leads to a TRD-like phenotype in mice, and modulation of brain-derived neurotrophic factor (BDNF) expression in the prefrontal cortex (PFC) appears to be one of the molecular determinants of the antidepressant response. In the present study, we observed that sustained KOR activation by a selective agonist, U50488, selectively reduced the levels of Bdnf transcripts II, IV, and Bdnf CDS (protein-coding Exon IX) in the PFC and cultured primary cortical neurons, which was blocked by selective KOR antagonist, norbinaltorphimine. Considering the crucial role of epigenetic pathways in BDNF expression, we further investigated the role of various epigenetic markers in KOR-induced BDNF downregulation in mice. We observed that treatment with U50488 resulted in selective and specific downregulation of acetylation at the ninth lysine residue of the histone H3 protein (H3K9ac) and upregulation of histone deacetylase 5 (HDAC5) expression in the PFC. Further, using anti-H3K9ac and anti-HDAC5 antibodies in the chromatin immune precipitation assay, we detected decreased enrichment of H3K9ac and increased HDAC5 binding at Bdnf II and IV transcripts after U50488 treatment, which were blocked by a selective KOR antagonist, norbinaltorphimine. Further mechanistic studies using HDAC5 selective inhibitor, LMK235, in primary cortical neurons and adeno-associated viral shRNA-mediated HDAC5-knockdown in the PFC of mice demonstrated an essential role of HDAC5 in KOR-mediated reduction of Bdnf expression in the PFC and in depression-like symptoms in mice. These results suggest that KOR engages multiple pathways to induce depression-like symptoms in mice and provide novel insights into the mechanisms by which activation of KOR regulates major depressive disorders.

Heat-Processed Soybean Germ Extract and Lactobacillus gasseri NK109 Supplementation Reduce LPS-Induced Cognitive Impairment and Colitis in Mice.

Soybean alleviates cognitive impairment. In our preparatory experiment, we found that dry-heat (90 °C for 30 min)-processed soybean embryo ethanol extract (hSE) most potently suppressed lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α expression in BV2 cells among dry-heat-, steaming-, and oil exclusion-processed soybean embryo ethanol extracts (SEs). Heat processing increased the absorbable soyasaponin Bb content of SE. Therefore, we investigated whether hSE and its supplement could mitigate LPS-impaired cognitive function in mice. Among dry-heat-, steaming-, and oil exclusion-processed SEs, hSE mitigated LPS-impaired cognitive function more than parental SE. hSE potently upregulated LPS-suppressed brain-derived neurotropic factor (BDNF) expression in the hippocampus, while LPS-induced TNF-α and IL-1β expression in the hippocampus and colon were downregulated. Lactobacillus gasseri NK109 additively increased the cognitive function-enhancing activity of hSE in mice with LPS-induced cognitive impairment as follows: the hSE and NK109 mix potently increased cognitive function and hippocampal BDNF expression and BDNF-positive neuron cell numbers and decreased TNF-α expression and NF-κB-positive cell numbers in the hippocampus and colon. These findings suggest that hSE and its supplement may decrease colitis and neuroinflammation by suppressing NF-κB activation and inducing BDNF expression, resulting in the attenuation of cognitive impairment.

Changes in brain-derived neurotropic factor following aerobic exercise

Changes in brain-derived neurotropic factor following aerobic exercise

Concomitant Exposure to Lower Doses of Arsenic, Lead, and Manganese Induces Greater Synergistic Neurotoxicity Than Individual Metals in Mice.

People in Bangladesh are often exposed to low to high levels of multiple metals due to contaminated groundwater with various heavy metals such as arsenic (As), lead (Pb), and manganese (Mn). However, the effects of concomitant exposure of these three metals on neurobehavioral changes are yet to be studied. Therefore, this study was intended to assess the neurotoxic effect of As, Pb, and Mn in a mouse model. Elevated plus maze (EPM) and Morris water maze (MWM) tests were conducted to evaluate anxiety, learning, and spatial memory impairment, respectively. The mice exposed to a combination of metals spent least time exploring the open arms and had longer latencies to find the hidden platform than the control and individual metal exposure groups in EPM and MWM tests. Moreover, concomitant multi-metal exposure remarkably decreased the activities of cholinergic and antioxidant enzymes, brain-derived neurotropic factor (BDNF), and nuclear factor erythroid 2-related factor 2 (Nrf2) levels and significantly increased interleukin-6 (IL-6) level in the brain tissue compared to the control and individual metal-exposed mice. Among the mice treated with a single metal, the As-treated mice showed the highest toxic effects than Pb- or Mn-treated mice. Taken together, the present study demonstrated that exposure to a mixture of As, Pb, and Mn, even at lower doses than individual metals, significantly augmented anxiety-like behavior and impaired learning and spatial memory compared to exposure to individual metals, which was associated with the changes of BDNF, Nrf2, IL-6 levels, and related enzyme activities in the brain.

The effect of an induced hypercholesteremia on the regulation of the ARC gene expression, Brain Derived Neurotropic Factor (BDNF), Synapsing-1 and neurotransmitter –glutamate in male rats

The effect of an induced hypercholesteremia on the regulation of the ARC gene expression, Brain Derived Neurotropic Factor (BDNF), Synapsing-1 and neurotransmitter –glutamate in male rats

The use of neuroleptics, sedatives and anesthetics for anxiolytic therapy in animals

An important area for improving antidepressant treatment is the expansion of the indications for neuroleptics, anesthetics and sedatives. All these drugs have pronounced neurotropic effects. The aim of our work is to study the published scientifc evidence on the potential of neuroleptics, anesthetics and sedatives for anxiolytic therapy. A systematic literature review was used to search for publications on the topic of the study. The PubMed database (https://pubmed.ncbi.nlm.nih.gov) was used to search for scientifc articles. The literature data indicates that ketamine is used to treat recurrent anxiety in both humans and animals. It provides rapid and sustained relief of anxiety symptoms in a variety of its clinical presentations. The anxiolytic effect occurs within the frst 12 hours after administration and remains effective for 1 to 2 weeks. The anxiolytic effect of ketamine is due to its effect on hippocampal neurotropic factor activity. Diazepam can signifcantly reduce anxiety and depressive symptoms as well as neuroinflammation in brain-injured mice. It causes a dose-dependent increase in motor activity. In combination with metformin, diazepam is the preferred treatment for type 2 diabetes mellitus in stressed animals. Intermittent use of diazepam is useful to avoid the development of physical dependence when the drug is used for a long period of time. Acepromazine is promising to be used for anxiolytic effect in animals. A combined protocol with acepromazine signifcantly reduced signs of stress, anxiety and aggression during veterinary visits and had an anxiolytic effect in dogs. Acepromazine reduces the negative effects of transport stress in wild ungulates. Dexmedetomidine is used for sedation in both human and veterinary medicine. This drug is a promising candidate for the experimental treatment of stress-related diseases such as anxiety disorders or post-traumatic stress disorder. We believe that further research in this area should be conducted in controlled comparative studies to determine the optimal doses and duration of administration of potential anxiolytics, considering the species, age, sex, physiological state and other relevant clinical parameters of the animals studied. Therefore, systematic and detailed studies will help us not only to understand the effectiveness, but also to provide safe and individualized treatment. This research can improve our understanding of the use of anxiolytics in veterinary practice, which is of key importance for improving the quality of animal welfare. In our opinion, the use of anesthetics, neuroleptics and sedatives, which are now widely used for sedation or general anesthesia, opens new possibilities for the treatment of behavioral and anxiety disorders in animals. Key words: anxiety, veterinary medicine, neuroleptics, sedatives, ketamine, acepromazine, diazepam, medetomidine.

Circulating netrin-1 levels are reduced and related to corneal nerve fiber loss in patients with diabetic neuropathy.

Deficiency of neurotropic factors is implicated in diabetic neuropathy (DN). Netrin-1 is a neurotropic factor, but its association with DN has not been explored. We have assessed the association between serum netrin-1 levels and early diabetic neuropathy assessed by quantifying corneal nerve fiber loss using corneal confocal microscopy. A total of 72 participants with type 2 diabetes, without and with corneal nerve fiber loss (DN- n = 42, DN+ n = 30), and 45 healthy controls were studied. Serum netrin-1 levels were measured by enzyme-linked immunosorbent assay, and corneal nerve morphology was assessed using corneal confocal microscopy. Corneal nerve fiber density, branch density, fiber length and serum netrin-1 levels were significantly lower in the DN- and DN+ groups compared with controls (P < 0.001). Netrin-1 levels correlated with corneal nerve fiber length in the DN+ group (r = 0.51; P < 0.01). A receiver operating characteristic curve analysis showed that a netrin-1 cut-off value of 599.6 (pg/mL) had an area under the curve of 0.85, with a sensitivity of 76% and specificity of 74% (P < 0.001; 95% confidence interval 0.76-0.94) for differentiating patients with and without corneal nerve loss. Serum netrin-1 levels show a progressive decline with increasing severity of small nerve fiber damage in patients with diabetes. Netrin-1 could act as a biomarker for small nerve fiber damage in DN.

Creating new in vitro models to examine the role of Pkd1 in cell and tubular physiology

Autosomal dominant polycystic kidney disease (ADPKD) results from loss of function mutations in polycystin proteins PC1 and PC2 encoded by the PKD1 and PKD2 genes. ADPKD affects 1 in 400 to 1 in 1000 people worldwide, with approximately 50% of patients progressing to end stage renal disease. The physiological function of the polycystins and the mechanisms of cystogenesis remain largely unknown. In vitro models may provide the clearest possibility to understand the immediate cell biological effects of polycystin loss, without the confounding second order injury that occurs as cysts develop. Some of the hurdles to in vitro models include clonal variation, renal segment heterogeneity, and inconsistent growth in 3D culture conditions. To address this need, we isolated renal epithelial cells from either the cortex or the medulla of Pkd1flox/flox; Pax8-rtTA; tetO-7-Cre mice crossed with the immorto-mouse expressing the temperature sensitive SV40 large T antigen. We then cloned single cells into isogenic cell lines, one cortical and one medullary. We verified the induction of Pkd1 KO by treating the cells with either 10 ug/ml doxycycline to knock out (KO) Pkd1 or vehicle control. Treatment continued for 7 days, after which Pkd1 KO was confirmed by western blot. Next, we sought to functionally characterize the two new cell lines. When the cells were grown on transwell supports, cells formed epithelial tight junctions with a trans-epithelial resistance of 2467 ohms/cm2. Resistance increased to 3130 ohms/cm2 following Pkd1 KO in the medullary clone. We next measured the rate of media acidification with or without Pkd1 KO as a proxy for glucose utilization. Pkd1 KO cells acidified faster than controls in both clones. Next, we addressed their ability to grow into tubuloids or spheroids / cysts in 3D culture using multiple approaches. Cells were either 1) suspended directly in Matrigel and plated in a 96 well plate, 2) suspended in Matrigel droplets, with multiple droplets adhering to an individual well of a 6 well plate, 3) plated within a Matrigel “sandwich”, or 4) plated within a sandwich and pulsed with glial derived neurotropic factor (GDNF) for 48 hours. All clones suspended directly in Matrigel formed spheroids, with more and larger spheroids in the Matrigel droplet cultures. Similar results were observed in the cortical clone grown in the sandwich, however the Pkd1 KO medullary clone in the same culture conditions had several giant spheroid structures at least 3 times larger than any other organoid observed in control medullary cultures. Finally, cortical cultures grown in the sandwich and pulsed with GDNF revealed larger spheroid structures in the Pkd1 KO cells than the control structures. Medullary cultures grown with GDNF revealed complicated structures with lumens and tubuloid projections in the controls, and large hollow spheroid / cystic structures in the Pkd1 KO cultures. Taken together, these data support the Matrigel sandwich with GDNF pulse may be the most useful to interrogate physiological changes in the absence of Pkd1 expression. In summary, we have created two new clonal cell lines with inducible Pkd1 KO, with isogenic controls, and the ability to differentiate into complicated tubuloids or spheroids in a genotypical manner, that may help elucidate the most proximate events occuring in renal epithelial cells after the inactivation of Pkd1. U54 DK126114. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of moderate intensity training and lithium on spatial learning and memory in a rat model: The role of SIRT3 and PGC1-α expression levels and brain-derived neurotropic factor

In this study we investigated the potential synergistic effects of moderate interval training (MIT) and lithium on spatial learning and memory. Forty-two male Wistar males were classified into six groups including I: Control, II: 10 mg/kg/day IP lithium (Li10), III: MIT, IV: Li10 + MIT, V: 40 mg/kg/day IP lithium (Li40), and VI: Li40 + MIT. Then, the rats underwent Morris Water Maze (MWM) test to assess their spatial memory and learning ability. Brain-derived neurotrophic factor (BDNF) density was measured by enzyme-linked immunosorbent assay (ELISA), and the expression of PGC1 and SIRT3 were assessed via qRT-PCR. The results show that MIT improves both memory and spatial learning; but lithium alone, does not cause this. Additionally, those exposed to a combination of exercise and lithium also had improved spatial learning and memory. Finally, we observed a positive role of BDNF protein, and PGC1 gene on the effects of exercise and lithium.

Lack of Direct Effects of Neurotrophic Factors in an In Vitro Model of Neuroinflammation.

Neuroinflammation is associated with several neurological disorders including temporal lobe epilepsy. Seizures themselves can induce neuroinflammation. In an in vivo model of epilepsy, the supplementation of brain-derived neurotropic factor (BDNF) and fibroblast growth factor-2 (FGF-2) using a Herpes-based vector reduced epileptogenesis-associated neuroinflammation. The aim of this study was to test whether the attenuation of the neuroinflammation obtained in vivo with BDNF and FGF-2 was direct or secondary to other effects, for example, the reduction in the severity and frequency of spontaneous recurrent seizures. An in vitro model of neuroinflammation induced by lipopolysaccharide (LPS, 100 ng/mL) in a mouse primary mixed glial culture was used. The releases of cytokines and NO were analyzed via ELISA and Griess assay, respectively. The effects of LPS and neurotrophic factors on cell viability were determined by performing an MTT assay. BDNF and FGF-2 were tested alone and co-administered. LPS induced a significant increase in pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and NO. BDNF, FGF-2, and their co-administration did not counteract these LPS effects. Our study suggests that the anti-inflammatory effect of BDNF and FGF-2 in vivo in the epilepsy model was indirect and likely due to a reduction in seizure frequency and severity.

The β-Secretase BACE1 Drives Fibroblast Activation in Systemic Sclerosis through the APP/β-Catenin/Notch Signaling Axis

The beta-amyloid precursor protein cleaving enzyme 1 (BACE1) is well known for its role in the development of Alzheimer’s disease. Recent publications, including our own, have demonstrated a role for this enzyme in other chronic diseases. The aim of this study was to investigate the role of BACE1 in the autoimmune disease systemic sclerosis (SSc). BACE1 protein levels were elevated in SSc patient skin. Inhibition of BACE1 with small molecule inhibitors or siRNA blocked SSc and fibrotic stimuli mediated fibroblast activation. Furthermore, we show that BACE1 regulation of dermal fibroblast activation is dependent on β-catenin and Notch signalling. The Neurotropic factor BDNF negatively regulates BACE1 expression and activity in dermal fibroblasts. Finally, sera from SSc patients show higher Aβ and lower BDNF levels compared to healthy controls. The ability of BACE1 to regulate SSc fibroblast activation reveals a therapeutic target in SSc. Several BACE1 inhibitors have been shown to be safe in clinical trials for Alzheimer’s disease and could be repurposed to ameliorate fibrosis progression.

Assessment of brain-derived neurotrophic factor levels in serum of children with autism spectrum disorders

BackgroundThe autism spectrum disorder (ASD) has no identified biomarker for early detection or for its severity. As for the brain-derived neurotrophic factor (BDNF), it is a crucial neurotropic factor that regulates the plasticity and maturing of neuronal synapses. Accordingly, it might influence how children with autism develop.MethodTo evaluate the BDNF serum levels in autistic children and their relationship with the illness severity as well as with the common drugs received by autistic patients, 60 patients with autism along with another 60 normally developing children were involved in the study. Using the Childhood Autism Rating Scale (CARS), the severity of autism was then evaluated. The ELISA method was used to measure the BDNF level.ResultsIt was seen that the BDNF concentrations were higher in autism patients (P < 0.001). There was also a highly strong positive association between the CARS score and the BDNF (P < 0.001). Using the cut-off value of > 2.8 of BDNF helped to distinguish between well-developing and autistic children, with the aspects of “sensitivity” and “specificity” being 88.3% and 80%, respectively. Moreover, children with autism who received omega-3 had statistically lower levels of BDNF than those who did not take any (P = 0.040).ConclusionThe serum BDNF concentration is higher in autism; this proposes that the BDNF may contribute to the onset or progress of autism. Therefore, it may be used as a noninvasive biomarker for the illness severity because of its greater occurrence in autistic children who have severe social impairment.

Transfection of the BDNF Gene in the Surviving Dopamine Neurons in Conjunction with Continuous Administration of Pramipexole Restores Normal Motor Behavior in a Bilateral Rat Model of Parkinson's Disease.

In Parkinson's disease (PD), progressive degeneration of nigrostriatal innervation leads to atrophy and loss of dendritic spines of striatal medium spiny neurons (MSNs). The loss disrupts corticostriatal transmission, impairs motor behavior, and produces nonmotor symptoms. Nigral neurons express brain-derived neurotropic factor (BDNF) and dopamine D3 receptors, both protecting the dopamine neurons and the spines of MSNs. To restore motor and nonmotor symptoms to normality, we assessed a combined therapy in a bilateral rat Parkinson's model, with only 30% of surviving neurons. The preferential D3 agonist pramipexole (PPX) was infused for four ½ months via mini-osmotic pumps and one month after PPX initiation; the BDNF-gene was transfected into the surviving nigral cells using the nonviral transfection NTS-polyplex vector. Overexpression of the BDNF-gene associated with continuous PPX infusion restored motor coordination, balance, normal gait, and working memory. Recovery was also related to the restoration of the average number of dendritic spines of the striatal projection neurons and the number of TH-positive neurons of the substantia nigra and ventral tegmental area. These positive results could pave the way for further clinical research into this promising therapy.