Neurotrophic Factor Gene Expression Research Articles

Fluoride exposure during pregnancy and lactation triggers oxidative stress and molecular changes in hippocampus of offspring rats

Long-term exposure to high concentrations of fluoride (F) can damage mineralized and soft tissues such as bones, liver, kidney, intestine, and nervous system of adult rats. The high permeability of the blood–brain barrier and placenta to F during pregnancy and lactation may be critical to neurological development. Therefore, this study aimed to investigate the effects of F exposure during pregnancy and lactation on molecular processes and oxidative biochemistry of offspring rats’ hippocampus. Pregnant Wistar rats were randomly assigned into 3 groups in accordance with the drinking water received: G1 – deionized water (control); G2 – 10 mg/L of F and G3 – 50 mg/L of F. The exposure to fluoridated water began on the first day of pregnancy and lasted until the 21st day of breastfeeding (when the offspring rats were weaned). Blood plasma samples of the offspring rats were collected to determine F levels. Hippocampi samples were collected for oxidative biochemistry analyses through antioxidant capacity against peroxyl (ACAP), lipid peroxidation (LPO), and nitrite (NO2−) levels. Also, brain-derived neurotrophic factor (BDNF) gene expression (RT-qPCR) and proteomic profile analyses were performed. The results showed that exposure to both F concentrations during pregnancy and lactation increased the F bioavailability, triggered redox imbalance featured by a decrease of ACAP, increase of LPO and NO2− levels, BDNF overexpression and changes in the hippocampus proteome. These findings raise novel questions regarding potential repercussions on the hippocampus structure and functioning in the different cognitive domains.

Low-Level Inhibition of GABAergic Synapses Enhances Gene Expressions Crucial for Neuronal Plasticity in the Hippocampus After Ischemic Stroke

ObjectivePharmacological inhibition of GABAergic synapses could represent a potent neuromodulation strategy to activate hippocampal neurons and increase neurotrophic factor gene expression, thus exerting a beneficial effect on post-stroke cognitive impairment (PSCI). The objective of this study was to assess the effects of low-level inhibition of GABAergic synapses on hippocampal gene expressions related to neuroplasticity using the middle cerebral artery occlusion surgery (MCAO) ischemic stroke rat model. MethodsThe animals were randomly assigned to three experimental groups—(1) a sham operated group (SHAM), (2) a control group (CON), and (3) a bicuculline group (BIC). MCAO was performed in the CON and BIC groups. A non-epileptic dose of bicuculline (0.25 mg/kg) was intraperitoneally administered every day for two weeks, starting three days after surgery, to the rats in the BIC group. The mRNA expression of brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), in relation to neurotrophic intracellular signal, p75, in relation to apoptosis, and synaptophysin (SYP) and PSD-95, synaptic markers, were assessed in the hippocampus ipsilateral to the ischemic site. ResultsMCAO increased the gene expression of TrkB. Furthermore, MCAO plus bicuculline administration increased the expression ratio of TrkB to p75 and SYP gene expression. ConclusionTherefore, this study showed that administration of bicuculline after stroke beneficially modulated the expression of crucial genes for neuroplasticity, including BDNF receptors and SYP, in the ipsilateral hippocampus, suggesting that low-level inhibition of GABAergic synapses could lead to beneficial neuromodulation in the hippocampus after stroke.

Isoflurane preconditioning effects on brain damage induced by electromagnetic pulse radiation through epigenetic modification of BDNF gene transcription.

The effects of electromagnetic pulse (EMP) radiation on cognitive impairment have attracted much attention, but the mechanism is still unclear. Regulation of brain-derived neurotrophic factor (BDNF) gene expression has been found to promote memory formation and neuronal survival. Isoflurane preconditioning (IP) was reported to have a neuroprotective effect. In this study, we verified the protective effect of IP against brain injury induced by EMP exposure and examined the relation of this effect with BDNF gene regulation. Twenty-four hours before EMP exposure, rats were pretreated with 2% inhaled isoflurane for 30 minutes. At 24 hours after EMP injury, the Morris water maze test was carried out. Meanwhile, the other rats were executed and their brain tissues were used for Nissl staining, qRT-PCR, western blot and chromatin immunoprecipitation. The Morris water maze results showed that 2% IP improved the spatial learning and memory ability of the rats. The Nissl staining results showed 2% of IP alleviated neuronal damage. Also, we detected the mRNA and protein expression of BDNF, and 2% IP significantly increased the expression of BDNF. We also found the expression level of histone deacetylase 2 (HDAC2) was increased and that EMP exposure significantly decreased H3 acetylation, while 2% IP reversed these phenomena, individually, BDNF transcription was activated, and neurogenesis after EMP exposure was alleviated. Our results suggested that 2% of IP alleviates cognitive impairment induced by EMP exposure in rats. Also, the sustained elevated level of BDNF gene transcription may be an essential mechanism for stimulating neurogenesis because of the increased level of HDAC2-dependent H3 acetylation.

Effects of maternal low-protein diet and spontaneous physical activity on the transcription of neurotrophic factors in the placenta and the brains of mothers and offspring rats.

Maternal protein restriction and physical activity can affect the interaction mother-placenta-fetus. This study quantified the gene expression of brain-derived neurotrophic factor (BDNF), neurothrophin 4, tyrosine kinase receptor B (TrkB/NTRK2), insulin-like growth factor (IGF-1), and insulin-like growth factor receptor (IGF-1r) in the different areas of mother's brain (hypothalamus, hippocampus, and cortex), placenta, and fetus' brain of rats. Female Wistar rats (n = 20) were housed in cages containing a running wheel for 4 weeks before gestation. According to the distance spontaneously traveled daily, rats were classified as inactive or active. During gestation, on continued access to the running wheel, active and inactive groups were randomized to receive normoprotein diet (18% protein) or a low-protein (LP) diet (8% protein). At day 20 of gestation, gene expression of neurotrophic factors was analyzed by quantitative polymerase chain reaction in different brain areas and the placenta. Dams submitted to a LP diet during gestation showed upregulation of IGF-1r and BDNF messenger RNA in the hypothalamus, IGF-1r and NTRK2 in the hippocampus, and BDNF, NTRK2, IGF-1 and IGF-1r in the cortex. In the placenta, there was a downregulation of IGF-1. In the brain of pups from mothers on LP diet, IGF-1r and NTRK2 were downregulated. Voluntary physical activity attenuated the effects of LP diet on IGF-1r in the hypothalamus, IGF-1r and NTRK2 in the hippocampus, IGF-1 in the placenta, and NTRK2 in the fetus' brain. In conclusion, both maternal protein restriction and spontaneous physical activity influence the gene expression of BDNF, NTRK2, IGF-1, and IGF-1r, with spontaneous physical activity being able to normalize in part the defects caused by protein restriction during pregnancy.

Neonatal Tactile Stimulation Alters Behaviors in Heterozygous Serotonin Transporter Male Rats: Role of the Amygdala.

The serotonin transporter (SERT) gene, especially the short allele of the human serotonin transporter linked polymorphic region (5-HTTLPR), has been associated with the development of stress-related neuropsychiatric disorders. In line, exposure to early life stress in SERT knockout animals contributes to anxiety- and depression-like behavior. However, there is a lack of investigation of how early-life exposure to beneficial stimuli, such as tactile stimulation (TS), affects later life behavior in these animals. In this study, we investigated the effect of TS on social, anxiety, and anhedonic behavior in heterozygous SERT knockouts rats and wild-type controls and its impact on gene expression in the basolateral amygdala. Heterozygous SERT+/– rats were submitted to TS during postnatal days 8–14, for 10 min per day. In adulthood, rats were assessed for social and affective behavior. Besides, brain-derived neurotrophic factor (Bdnf) gene expression and its isoforms, components of glutamatergic and GABAergic systems as well as glucocorticoid-responsive genes were measured in the basolateral amygdala. We found that exposure to neonatal TS improved social and affective behavior in SERT+/– animals compared to naïve SERT+/– animals and was normalized to the level of naïve SERT+/+ animals. At the molecular level, we observed that TS per se affected Bdnf, the glucocorticoid-responsive genes Nr4a1, Gadd45β, the co-chaperone Fkbp5 as well as glutamatergic and GABAergic gene expression markers including the enzyme Gad67, the vesicular GABA transporter, and the vesicular glutamate transporter genes. Our results suggest that exposure of SERT+/– rats to neonatal TS can normalize their phenotype in adulthood and that TS per se alters the expression of plasticity and stress-related genes in the basolateral amygdala. These findings demonstrate the potential effect of a supportive stimulus in SERT rodents, which are more susceptible to develop psychiatric disorders.

Protective effect of Lactobacillus salivarius Li01 on thioacetamide-induced acute liver injury and hyperammonaemia.

The gut microbiota plays pivotal roles in liver disease onset and progression. The protective effects of Lactobacillus salivarius Li01 on liver diseases have been reported. In this study, we aimed to detect the protective effect of L. salivarius Li01 on thioacetamide (TAA)-induced acute liver injury and hyperammonaemia. C57BL/6 mice were separated into three groups and given a gavage of L. salivarius Li01 or phosphate-buffered saline for 7days. Acute liver injury and hyperammonaemia were induced with an intraperitoneal TAA injection. L. salivarius Li01 decreased mortality and serum transaminase levels and improved histological liver damage caused by TAA. Serum inflammatory cytokine and chemokine and lipopolysaccharide-binding protein (LBP) concentrations, nuclear factor κB (NFκB) pathway activation and macrophage and neutrophil infiltration into the liver were significantly alleviated by L. salivarius Li01. L. salivarius Li01 also reinforced gut barrier and reshaped the perturbed gut microbiota by upregulating Bacteroidetes and Akkermansia richness and downregulating Proteobacteria, Ruminococcaceae_UCG_014 and Helicobacter richness. Plasma and faecal ammonia levels declined noticeably in the Li01 group, accompanied by improvements in cognitive function, neuro-inflammation and relative brain-derived neurotrophic factor (BDNF) gene expression. Our results indicated that L. salivarius Li01 could be considered a potential probiotic in acute liver injury and hepatic encephalopathy (HE).

The Effect of Endurance Exercise Training on the Expression of Brain Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) Genes of the Cerebellum in Diabetic Rat

Objective: Few studies have been conducted on variations of the central nervous system of diabetic patients and much fewer investigations done on the cerebellum of diabetes patients. The current research aims to investigate the effect of endurance training on neurotrophic factors affecting the cerebellum in the diabetic rat. Materials and Methods: This study is experimental.Twenty Wistar rat were randomly allocated in four groups including: (1) control (n=5), (2) diabetic exercise (n=5), (3) healthy-control (n=5), (4) and exercise-healthy (n=5). Diabetes were induced by intraperitoneal Streptozotocin injection. The endurance exercise training was performed at moderate intensity for six weeks. Expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) genes were measured using the Real-Time PCR method in the cerebellum of the rat. Two-way ANOVA test was used for comparing the means of expression of genes between groups. All statistical analyses were done using SPSS 22 software. Results: A significant increase was observed in the expression of NGF (from 1.03±0.11 to 1.61±0.24; P-value≤ 0.05) and BDNF (from 1.59±0.06 to 3.24±0.46; P-value≤ 0.05) genes in male rats with experimental diabetes and healthy subjects after six weeks endurance training. Conclusion: Endurance training may be helpful for diabetic patients by increasing the neurotrophic factors and thereby preventing diabetes-related neural complications.

Purification of Fibroblasts and Schwann Cells from Sensory and Motor Nerves in Vitro.

The principal cells in the peripheral nervous system are the Schwann cells (SCs) and the fibroblasts. Both these cells distinctly express the sensory and motor phenotypes involved in different patterns of neurotrophic factor gene expression and other biological processes, affecting nerve regeneration. The present study has established a protocol to obtain highly purified rat sensory and motor SCs and fibroblasts more rapidly. The ventral root (motor nerve) and the dorsal root (sensory nerve) of neonatal rats (7-days-old) were dissociated and the cells were cultured for 4-5 days, followed by isolation of sensory and motor fibroblasts and SCs by combining differential digestion and differential adherence methods sequentially. The results of immunocytochemistry and flow cytometry analyses showed that the purity of the sensory and motor SCs and fibroblasts were >90%. This protocol can be used to obtain a large number of sensory and motor fibroblasts/SCs more rapidly, contributing to the exploration of sensory and motor nerve regeneration.

9-Methyl-\u03b2-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes

β-Carbolines (BC) are pyridoindoles, which can be found in various exogenous and endogenous sources. Recent studies revealed neurostimulative, neuroprotective, neuroregenerative and anti-inflammatory effects of 9-methyl-BC (9-Me-BC). Additionally, 9-me-BC increased neurite outgrowth of dopaminergic neurons independent of dopamine uptake into these neurons. In this study, the role of astrocytes in neurostimulative, neuroregenerative and neuroprotective properties of 9-me-BC was further explored.9-Me-BC exerted anti-proliferative effects without toxic properties in dopaminergic midbrain and cortical astrocyte cultures. The organic cation transporter (OCT) but not the dopamine transporter seem to mediate at least part the effect of 9-me-BC on astrocytes. Remarkably, 9-me-BC stimulated the gene expression of several important neurotrophic factors for dopaminergic neurons like Artn, Bdnf, Egln1, Tgfb2 and Ncam1. These factors are well known to stimulate neurite outgrowth and to show neuroprotective and neuroregenerative properties to dopaminergic neurons against various toxins. Further, we show that effect of 9-me-BC is mediated through phosphatidylinositol 3-kinase (PI3K) pathway. Additionally, 9-me-BC showed inhibitory properties to monoamine oxidase (MAO) activity with an IC50 value of 1 µM for MAO-A and of 15.5 µM for MAO-B. The inhibition of MAO by 9-me-BC might contribute to the observed increased dopamine content and anti-apoptotic properties in cell culture after 9-me-BC treatment in recent studies. Thus, 9-me-BC have a plethora of beneficial effects on dopaminergic neurons warranting its exploration as a new multimodal anti-parkinsonian medication.

A Comparative Analysis of Multipotent Mesenchymal Stromal Cells derived from Different Sources, with a Focus on Neuroregenerative Potential

Multipotent mesenchymal stromal cells (MSCs) can be considered an accessible therapeutic tool for regenerative medicine. Here, we compared the growth kinetics, immunophenotypic and immunomodulatory properties, gene expression and secretome profile of MSCs derived from human adult bone marrow (BM-MSCs), adipose tissue (AT-MSCs) and Wharton’s jelly (WJ-MSCs) cultured in clinically-relevant conditions, with the focus on the neuroregenerative potential. All the cell types were positive for CD10/CD29/CD44/CD73/CD90/CD105/HLA-ABC and negative for CD14/CD45/CD235a/CD271/HLA-DR/VEGFR2 markers, but they differed in the expression of CD34/CD133/CD146/SSEA-4/MSCA-1/CD271/HLA-DR markers. BM-MSCs displayed the highest immunomodulatory activity compared to AT- and WJ-MSCs. On the other hand, BM-MSCs secreted the lower content and had the lower gene expression of neurotrophic growth factors compared to other cell lines, which may be caused by the higher sensitivity of BM-MSCs to nutrient limitations. Despite the differences in growth factor secretion, the MSC secretome derived from all cell sources had a pronounced neurotrophic potential to stimulate the neurite outgrowth of DRG-neurons and reduce the cell death of neural stem/progenitor cells after H2O2 treatment. Overall, our study provides important information for the transfer of basic MSC research towards clinical-grade manufacturing and therapeutic applications.

Antineuropathic pain actions of Wu-tou decoction resulted from the increase of neurotrophic factor and decrease of CCR5 expression in primary rat glial cells

Wu-tou decoction (WTD), a classic Traditional Chinese medicine formula, has been extensively used in the treatment of neuropathic pain (NP) such as chronic inflammatory pain, trigeminal neuralgia, and cancer-induced pain. Our previous studies have shown that the severity of mechanical allodynia and thermo hypersensitivity in NP rats are reduced by WTD, of which analgesic candidates are paeoniflorin (Pae) and liquiritin (Liq). The aim of this study was to clarify the molecular mechanisms of WTD, Pae and Liq against NP based on the primary rat glial cells in vitro. The gene expression levels of neurotrophic factors such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and Artemin and C-C chemokine receptor type 5 (CCR5) were augmented by inflammatory cytokines, while chemokines increased only CCR5 gene expression. The constitutive and cytokine-augmented neurotrophic factor gene expression was enhanced by WTD, Pae, and Liq through PI3K- and PKA-dependent pathways in rat glial cells, leading to the increase of NGF and BDNF production. Furthermore, the CCR5 gene expression under basal and chemokine-treated conditions was suppressed by these reagents, in which signal pathway(s) was independent on the activation of PI3K and PKA. Moreover, there was no cytotoxicity in the WTD, Pae, and Liq treatments in glial cells. Thus, these results provide a novel evidence that WTD may exert the anti-NP actions by predominantly increasing the production of neurotrophic factors through PI3K- and PKA-signaling pathways in rat glial cells. Furthermore, Pae and Liq may play as analgesic candidates in WTD-mediated NP management.

In Vivo and In Vitro Evaluation of a Novel Hyaluronic Acid–Laminin Hydrogel as Luminal Filler and Carrier System for Genetically Engineered Schwann Cells in Critical Gap Length Tubular Peripheral Nerve Graft in Rats

In the current study we investigated the suitability of a novel hyaluronic acid–laminin hydrogel (HAL) as luminal filler and carrier system for co-transplanted cells within a composite chitosan-based nerve graft (CNG) in a rat critical nerve defect model. The HAL was meant to improve the performance of our artificial nerve guides by giving additional structural and molecular support to regrowing axons. We filled hollow CNGs or two-chambered nerve guides with an inserted longitudinal chitosan film (CNG[F]s), with cell-free HAL or cell-free HA or additionally suspended either naïve Schwann cells (SCs) or fibroblast growth factor 2-overexpressing Schwann cells (FGF2-SCs) within the gels. We subjected female Lewis rats to immediate 15 mm sciatic nerve gap reconstruction and comprehensively compared axonal and functional regeneration parameters with the gold standard autologous nerve graft (ANG) repair. Motor recovery was surveyed by means of electrodiagnostic measurements at 60, 90, and 120 days post-reconstruction. Upon explantation after 120 days, lower limb target muscles were harvested for calculation of muscle-weight ratios. Semi-thin cross-sections of nerve segments distal to the grafts were evaluated histomorphometrically. After 120 days of recovery, only ANG treatment led to full motor recovery. Surprisingly, regeneration outcomes revealed no regeneration-supportive effect of HAL alone and even an impairment of peripheral nerve regeneration when combined with SCs and FGF2-SCs. Furthermore, complementary in vitro studies, conducted to elucidate the reason for this unexpected negative result, revealed that SCs and FGF2-SCs suspended within the hydrogel relatively downregulated gene expression of regeneration-supporting neurotrophic factors. In conclusion, cell-free HAL in its current formulation did not qualify for optimizing regeneration outcome through CNG[F]s. In addition, we demonstrate that our HAL, when used as a carrier system for co-transplanted SCs, changed their gene expression profile and deteriorated the pro-regenerative milieu within the nerve guides.

Rasagiline antiremodeling action after myocardial infarction may be mediated by circadian rhythm and neurotrophic related gene expression changes

Rasagiline mesylate (RG) is a potent, selective, irreversible monoamine oxidase-B inhibitor, developed to prolong the action of dopamine in the brain. It may rescue degenerating dopamine neurons through inhibiting death signal transduction initiated by the mitochondria permeability transition pore. We have previously shown that it decreases post-experimental infarct remodeling (REM). We investigated whether this cardioprotective result could be due to centrally mediated actions. In a rat model undergoing experimental myocardial infarction (MI) by a permanent ligation of the left anterior descending coronary artery. RG was administered, intraperitoneally for 28 days (2 mg/kg) starting 24 hours after MI induction. Treatment with RG significantly ameliorated cardiac REM echocardiographically as we have previously shown. In order to identify potential new cardioprotective mechanisms of RG action after MI, a comparative RNA expression analysis of remote region cardiac tissue was performed in placebo (Normal saline- NS), RG and Sham samples. RNA-seq analysis results were also confirmed by real time PCR. Our analysis showed: – differential RNA expression of circadian rhythm in NS samples versus RG. Circadian related genes Per3, Ciart, Dbp, Hpd, Nr1d2, and Rev-erb were upregulated while Arntl gene was downregulated (all P < 0.01); – as regards neurotrophic genes, neuropeptide Y (Npy) and neurogranin (Nrgn) genes were downregulated in RG samples compared to NS while the Brain-Derived Neurotrophic Factor (Bdnf) was upregulated (all P < 0.01). Our findings indicate that MI injury influences in a protective manner the expression of circadian rhythm and neurotrophic factor genes in cardiac tissue; potential regulation of these genes is part of the novel cardioprotective mechanism of RG action described, further advocating the possible use of this drug post-MI.

Combination of olfactory ensheathing cells and human umbilical cord mesenchymal stem cell-derived exosomes promotes sciatic nerve regeneration.

Olfactory ensheathing cells (OECs) are promising seed cells for nerve regeneration. However, their application is limited by the hypoxic environment usually present at the site of injury. Exosomes derived from human umbilical cord mesenchymal stem cells have the potential to regulate the pathological processes that occur in response to hypoxia. The ability of OECs to migrate is unknown, especially in hypoxic conditions, and the effect of OECs combined with exosomes on peripheral nerve repair is not clear. Better understanding of these issues will enable the potential of OECs for the treatment of nerve injury to be addressed. In this study, OECs were acquired from the olfactory bulb of Sprague Dawley rats. Human umbilical cord mesenchymal stem cell-derived exosomes (0-400 μg/mL) were cultured with OECs for 12-48 hours. After culture with 400 μg/mL exosomes for 24 hours, the viability and proliferation of OECs were significantly increased. We observed changes to OECs subjected to hypoxia for 24 hours and treatment with exosomes. Exosomes significantly promoted the survival and migration of OECs in hypoxic conditions, and effectively increased brain-derived neurotrophic factor gene expression, protein levels and secretion. Finally, using a 12 mm left sciatic nerve defect rat model, we confirmed that OECs and exosomes can synergistically promote motor and sensory function of the injured sciatic nerve. These findings show that application of OECs and exosomes can promote nerve regeneration and functional recovery. This study was approved by the Institutional Ethical Committee of the Air Force Medical University, China (approval No. IACUC-20181004) on October 7, 2018; and collection and use of human umbilical cord specimens was approved by the Ethics Committee of the Linyi People's Hospital, China (approval No. 30054) on May 20, 2019.

Controlling properties of human neural progenitor cells using 2D and 3D conductive polymer scaffolds

Human induced pluripotent stem cell-derived neural progenitor cells (hNPCs) are a promising cell source for stem cell transplantation to treat neurological diseases such as stroke and peripheral nerve injuries. However, there have been limited studies investigating how the dimensionality of the physical and electrical microenvironment affects hNPC function. In this study, we report the fabrication of two- and three-dimensional (2D and 3D respectively) constructs composed of a conductive polymer to compare the effect of electrical stimulation of hydrogel-immobilized hNPCs. The physical dimension (2D vs 3D) of stimulating platforms alone changed the hNPCs gene expression related to cell proliferation and metabolic pathways. The addition of electrical stimulation was critical in upregulating gene expression of neurotrophic factors that are important in regulating cell survival, synaptic remodeling, and nerve regeneration. This study demonstrates that the applied electrical field controls hNPC properties depending on the physical nature of stimulating platforms and cellular metabolic states. The ability to control hNPC functions can be beneficial in understanding mechanistic changes related to electrical modulation and devising novel treatment methods for neurological diseases.

Decreased Expression of Cerebral Dopamine Neurotrophic Factor in Platelets of Stroke Patients

BackgroundCerebral dopamine neurotrophic factor plays a critical role in repairing and maintaining healthy neurons in pathological conditions such as stroke. However, the association between cerebral dopamine neurotrophic factor expression and stroke has only recently been investigated in preclinical models and is rarely described in human studies. ObjectivesThe aims of this were to examine neurological alterations mirrored in human blood platelet cerebral dopamine neurotrophic factor gene expression. Cerebral dopamine neurotrophic factor is expressed in both the central nervous system and peripheral blood. Blood platelets are often used to model neuronal behavior because they exhibit biochemical impairments similar to brain tissues of patients with neurological disorders. MethodsRNA was isolated from platelets and cDNA was synthesized to quantify cerebral dopamine neurotrophic factor gene expression of 36 stroke patients compared to 72 healthy aged-matched controls through real-time PCR. Further grouping analyses of data with regard to age, sex, and medication history were performed. ResultsCerebral dopamine neurotrophic factor gene expression was significantly reduced in stroke patients relative to control subjects (P = .013). Subsequent analysis revealed a significant difference in expression between males and females within the control group (P = .026). Decreased cerebral dopamine neurotrophic factor expression was only observed in male stroke patients compared to their sex-matched controls (P = .008). Grouping stroke patients based on their medication history did not significantly alter cerebral dopamine neurotrophic factor gene expression. ConclusionsFurther studies investigating cerebral dopamine neurotrophic factor expression could be directed towards the interplay of the central nervous system, hematopoietic derivatives, and utilizing cerebral dopamine neurotrophic factor as a therapeutic tool.

Acute stress in adolescence vs early adulthood following selective deletion of dysbindin-1A: Effects on anxiety, cognition and other schizophrenia-related phenotypes

As exposure to stress has been linked to the onset and maintenance of psychotic illness, its pathogenesis may involve environmental stressors interacting with genetic vulnerability. To establish whether acute stress interacts with a targeted mutation of the gene encoding the neurodevelopmental factor dystrobrevin-binding protein 1 (DTNBP1), resulting in a specific loss of the isoform dysbindin-1A, to influence schizophrenia-relevant phenotypes in mice during adolescence and adulthood. Male and female mice with a heterozygous or homozygous deletion of DTNBP1 were assessed in the open field test following acute restraint stress in adolescence (Day 35) and young adulthood (Day 60-70). Effects of acute restraint stress on memory retention in the novel object recognition test was also assessed in adulthood. Baseline corticosterone was measured in serum samples and, brain-derived neurotrophic factor (BDNF), glucocorticoid and mineralocorticoid receptor gene expression levels were measured in the hippocampus of adult mice. In the open field, deletion of dysbindin-1A induced hyperactivity and attenuated the action of stress to reduce hyperactivity in adolescence but not in adulthood; in females deletion of dysbindin-1A attenuated the effect of acute stress to increase anxiety-related behaviour in adolescence but not in adulthood. In the novel object recognition test, deletion of dysbindin-1A impaired memory and also revealed an increase in anxiety-related behaviour and a decrease in hippocampal BDNF gene expression in males. These data suggest that deletion of dysbindin-1A influences behaviours related to schizophrenia and anxiety more robustly in adolescence than in adulthood and that dysbindin-1A influences stress-related responses in a sex-dependent manner.

The effect of rotenone on synuclein and neurotrophic factor gene expression levels in zebrafish larvae

The effect of rotenone on synuclein and neurotrophic factor gene expression levels in zebrafish larvae

A study of limbic brain derived neurotrophic factor gene expression in male Sprague-Dawley rats trained on a learned helplessness task

BackgroundBrain derived neurotrophic factor (BDNF) has been linked to the etiology and pathology of Major Depressive Disorder (MDD). Here, the relationship between learned helplessness (LH), a cognitive/motivational state relevant to MDD, and BDNF mRNA in various limbic regions, was investigated. MethodsIn Sprague-Dawley male rats, LH was induced by escape training, using a triadic design of stressor controllability involving exposure to no shocks (NS), escapable shocks (ES) or yoked inescapable shocks (IES). LH was subsequently assessed in an active avoidance task, and levels of BDNF mRNA in limbic brain regions were compared across the triad following testing. ResultsAlthough the IES group displayed greater LH, BDNF mRNA levels were lower in the hippocampus and higher in the nucleus accumbens of both IES and ES groups. In contrast, BDNF mRNA in the basolateral amygdala was elevated only in rats exposed to IES. ConclusionThese results suggest that the inability to control an aversive stimulus can lead to a LH behavioural phenotype that is associated with region-specific alterations of BDNF gene expression in limbic nuclei.

Brain-derived neurotrophic factor (BDNF) and TrkB hippocampal gene expression are putative predictors of neuritic plaque and neurofibrillary tangle pathology

IntroductionDownregulation of brain-derived neurotrophic factor (BDNF) and its cognate neurotrophin receptor, TrkB, were observed during the progression of dementia, but whether the Alzheimer's disease (AD) pathological lesions diffuse plaques, (DPs), neuritic plaques (NPs), and neurofibrillary tangles (NFTs) are related to this alteration remains to be clarified. MethodsNegative binomial (NB) regressions were performed using gene expression data accrued from a single population of CA1 pyramidal neurons and regional hippocampal dissections obtained from participants in the Rush Religious Orders Study (RROS). ResultsDownregulation of Bdnf is independently associated with increased entorhinal cortex NPs. Downregulation of TrkB is independently associated with increased entorhinal cortex NFTs and CA1 NPs during the progression of AD. DiscussionResults indicate that BDNF and TrkB dysregulation contribute to AD neuropathology, most notably hippocampal NPs and NFTs. These data suggest attenuating BDNF/TrkB signaling deficits either at the level of BDNF, TrkB, or downstream of TrkB signaling may abrogate NPs and/or NFTs.