BDNF Gene Expression Research Articles

Induction of microglia activation after infection with the non-neurotropic A/CA/04/2009 H1N1 influenza virus.

Although influenza is primarily a respiratory disease, it has been shown, in some cases, to induce encephalitis, including people acutely infected with the pandemic A/California/04/2009 (CA/09) H1N1 virus. Based on previous studies showing that the highly pathogenic avian influenza (HPAI) A/Vietnam/1203/2004 H5N1 virus was neurotropic, induced CNS inflammation and a transient parkinsonism, we examined the neurotropic and inflammatory potential of the CA/09 H1N1 virus in mice. Following intranasal inoculation, we found no evidence for CA/09 H1N1 virus neurotropism in the enteric, peripheral or central nervous systems. We did, however, observe a robust increase in microglial activity in the brain characterized by an increase in the number of activated Iba-1-positive microglia in the substantia nigra (SN) and the hippocampus, despite the absence of virus in the brain. qPCR analysis in SN tissue showed that the induction of microgliosis was preceded by reduced gene expression of the neurotrophic factors bdnf, and gdnf and increases in the immune modulatory chemokine chemokine (C-C motif) ligand 4 (ccl4). We also noted changes in the expression of transforming growth factor-1 (tgfβ1) in the SN starting at 7 days post-infection (dpi) that was sustained through 21 dpi, coupled with increases in arginase-1 (arg1) and csf1, M2 markers for microglia. Given that neuroinflammation contributes to generation and progression of a number of neurodegenerative disorders, these findings have significant implications as they highlight the possibility that influenza and perhaps other non-neurotropic viruses can initiate inflammatory signals via microglia activation in the brain and contribute to, but not necessarily be the primary cause of, neurodegenerative disorders.

Chronic Binge Alcohol Administration in Simian Immunodeficiency Virus‐Infected Rhesus Macaques Modulates Pre‐Frontal Cortex Expression of Brain‐Derived Neurotrophic Factor and Microtubule‐Associated Protein 2

Persons living with HIV/AIDS have a higher incidence of alcohol use and abuse. Previous studies by our group revealed that chronic binge alcohol (CBA) administration unmasks cognitive deficits in SIV-infected rhesus macaques. Chronic alcohol abuse and HIV infection result in loss of neurotrophic factors and neurons. We hypothesized that CBA administration would synergize with SIV to produce greater suppression of neurotrophic factor expression compared to SUC/SIV. Rhesus macaques were fitted with an intra-gastric catheter for delivery of alcohol (CBA, n = 7) or isocaloric sucrose (SUC, n = 7) for the duration of the experiment. Macaques were infected with SIVmac251 three months after initiation of CBA or SUC, one SUC animal was not infected. Macaques were euthanized when end-stage criteria were met (∼4 or 18 months post-inoculation), brains were excised and dissected. Pre-frontal cortex (PFC), caudate (Cd) and hippocampus (Hp) were used for analysis of tissue viral load and gene expression of BDNF and MAP2. Viral load was not significantly different in CBA animals or between brain regions. PFC was the only brain in which viral load was above the limit of detection in all animals. BDNF expression was lower in CBA/SIV only in the PFC (p=NS). MAP2 expression was lower in PFC and Cd (p=NS). Gene expression of MAP2 was positively correlated with BDNF in the PFC (p<0.01), Cd (p<0.01) and Hp (p=0.03). The results suggest that the PFC is most susceptible to combined SIV and CBA insult. Supported by AA07577, AA09803, AA11290.

Methionine increases BDNF DNA methylation and improves memory in epilepsy.

ObjectiveTemporal lobe epilepsy (TLE) patients exhibit signs of memory impairments even when seizures are pharmacologically controlled. Surprisingly, the underlying molecular mechanisms involved in TLE-associated memory impairments remain elusive. Memory consolidation requires epigenetic transcriptional regulation of genes in the hippocampus; therefore, we aimed to determine how epigenetic DNA methylation mechanisms affect learning-induced transcription of memory-permissive genes in the epileptic hippocampus.MethodsUsing the kainate rodent model of TLE and focusing on the brain-derived neurotrophic factor (Bdnf) gene as a candidate of DNA methylation-mediated transcription, we analyzed DNA methylation levels in epileptic rats following learning. After detection of aberrant DNA methylation at the Bdnf gene, we investigated functional effects of altered DNA methylation on hippocampus-dependent memory formation in our TLE rodent model.ResultsWe found that behaviorally driven BdnfDNA methylation was associated with hippocampus-dependent memory deficits. Bisulfite sequencing revealed that decreased BdnfDNA methylation levels strongly correlated with abnormally high levels of BdnfmRNA in the epileptic hippocampus during memory consolidation. Methyl supplementation via methionine (Met) increased BdnfDNA methylation and reduced BdnfmRNA levels in the epileptic hippocampus during memory consolidation. Met administration reduced interictal spike activity, increased theta rhythm power, and reversed memory deficits in epileptic animals. The rescue effect of Met treatment on learning-induced BdnfDNA methylation, Bdnf gene expression, and hippocampus-dependent memory, were attenuated by DNA methyltransferase blockade.InterpretationOur findings suggest that manipulation of DNA methylation in the epileptic hippocampus should be considered as a viable treatment option to ameliorate memory impairments associated with TLE.

Ovariectomy does not exacerbate the negative effects of sleep deprivation on synaptic plasticity in rats

In our previous work, we found that female rats showed more cognitive impairment than male rats following 72h sleep deprivation (SD). Here, we compared the intact female with ovariectomized (OVX) rats to assess the potential modulatory effects of endogenous female sex hormones against the 48h SD-induced cognitive and synaptic modulations. The multiple platform method was applied for SD induction and spatial performances were determined using Morris water maze (MWM) task. Early longterm potentiation (E-LTP) was evaluated in area CA1 of the hippocampus and PCR and western blotting assays were employed to assess hippocampal BDNF gene and protein expression. To reveal any influence of sleep loss on stress level, we also measured the plasma corticosterone levels of animals. Regardless of reproductive status, SD significantly impaired short-term memory and LTP, but did not significantly change the BDNF expression in the hippocampus. The corticosterone levels were decreased in both intact and OVX female rats following SD. These findings suggest that depletion of female sex steroid hormones does not lead to any heightened responsivity of female animals to the negative effects of SD on cognitive and synaptic functions.

Transcriptomic analysis and 3D bioengineering of astrocytes indicate ROCK inhibition produces cytotrophic astrogliosis.

Astrocytes provide trophic, structural and metabolic support to neurons, and are considered genuine targets in regenerative neurobiology, as their phenotype arbitrates brain integrity during injury. Inhibitors of Rho kinase (ROCK) cause stellation of cultured 2D astrocytes, increased L-glutamate transport, augmented G-actin, and elevated expression of BDNF and anti-oxidant genes. Here we further explored the signposts of a cytotrophic, “healthy” phenotype by data-mining of our astrocytic transcriptome in the presence of Fasudil. Gene expression profiles of motor and autophagic cellular cascades and inflammatory/angiogenic responses were all inhibited, favoring adoption of an anti-migratory phenotype. Like ROCK inhibition, tissue engineered bioscaffolds can influence the extracellular matrix. We built upon our evidence that astrocytes maintained on 3D poly-ε-caprolactone (PCL) electrospun scaffolds adopt a cytotrophic phenotype similar to that produced by Fasudil. Using these procedures, employing mature 3D cultured astrocytes, Fasudil (100 μM) or Y27632 (30 μM) added for the last 72 h of culture altered arborization, which featured numerous additional minor processes as shown by GFAP and AHNAK immunolabelling. Both ROCK inhibitors decreased F-actin, but increased G-actin labeling, indicative of disassembly of actin stress fibers. ROCK inhibitors provide additional beneficial effects for bioengineered 3D astrocytes, including enlargement of the overall arbor. Potentially, the combined strategy of bio-compatible scaffolds with ROCK inhibition offers unique advantages for the management of glial scarring. Overall these data emphasize that manipulation of the astrocyte phenotype to achieve a “healthy biology” offers new hope for the management of inflammation in neuropathologies.

Epigenetic basis of opiate suppression of Bdnf gene expression in the ventral tegmental area.

Brain-derived neurotrophic factor (BDNF) plays a crucial role in modulating neural and behavioral plasticity to drugs of abuse. Here, we demonstrate a persistent down-regulation of exon-specific Bdnf expression in the ventral tegmental area (VTA) in response to chronic opiate exposure, which is mediated by specific epigenetic modifications at the corresponding Bdnf gene promoters. Exposure to chronic morphine increases stalling of RNA polymerase II at these Bdnf promoters in VTA and alters permissive and repressive histone modifications and occupancy of their regulatory proteins at the specific promoters. Furthermore, we show that morphine suppresses binding of phospho-CREB (cAMP response element binding protein) to Bdnf promoters in VTA, which results from enrichment of trimethylated H3K27 at the promoters, and that decreased NURR1 (nuclear receptor related-1) expression also contributes to Bdnf repression and associated behavioral plasticity to morphine. These studies reveal novel epigenetic mechanisms of morphine-induced molecular and behavioral neuroadaptations.

Somatostatin, neuronal vulnerability and behavioral emotionality.

Somatostatin (SST) deficits are common pathological features in depression and other neurological disorders with mood disturbances, but little is known about the contribution of SST deficits to mood symptoms or causes of these deficits. Here we show that mice lacking Sst (SstKO) exhibit elevated behavioral emotionality, high basal plasma corticosterone and reduced gene expression of Bdnf, Cortistatin, and Gad67, together recapitulating behavioral, neuroendocrine and molecular features of human depression. Studies in SstKO and heterozygous (SstHZ) mice show that elevated corticosterone is not sufficient to reproduce the behavioral phenotype, suggesting a putative role for Sst cell-specific molecular changes. Using laser-capture microdissection, we show that cortical SST-positive interneurons display significantly greater transcriptome deregulations after chronic stress compared to pyramidal neurons. Protein translation through eukaryotic initiation factor 2 (EIF2) signaling, a pathway previously implicated in neurodegenerative diseases, was most affected and suppressed in stress-exposed SST neurons. We then show that activating EIF2 signaling through EIF2 kinase inhibition mitigated stress-induced behavioral emotionality in mice. Together, our data suggest that (1) low SST plays a causal role in mood-related phenotypes, (2) deregulated EIF2-mediated protein translation may represent a mechanism for vulnerability of SST neurons, and (3) that global EIF2 signaling has antidepressant/anxiolytic potential.

Lithium-induced neuroprotection is associated with epigenetic modification of specific BDNF gene promoter and altered expression of apoptotic-regulatory proteins.

Bipolar disorder (BD), one of the most debilitating mental disorders, is associated with increased morbidity and mortality. Lithium is the first line of treatment option for BD and is often used for maintenance therapy. Recently, the neuroprotective action of lithium has gained tremendous attention, given that BD is associated with structural and functional abnormalities of the brain. However, the precise molecular mechanism by which lithium exerts its neuroprotective action is not clearly understood. In hippocampal neurons, the effects of lithium (1 and 2 mM) on neuronal viability against glutamate-induced cytotoxicity, dendritic length and number, and expression and methylation of BDNF promoter exons and expression of apoptotic regulatory genes were studied. In rat hippocampal neurons, lithium not only increased dendritic length and number, but also neuronal viability against glutamate-induced cytotoxicity. While lithium increased the expression of BDNF as well as genes associated with neuroprotection such as Bcl2 and Bcl-XL, it decreased the expression of pro-apoptotic genes Bax, Bad, and caspases 3. Interestingly, lithium activated transcription of specific exon IV to induce BDNF gene expression. This was accompanied by hypomethylation of BDNF exon IV promoter. This study delineates mechanisms by which lithium mediates its effects in protecting neurons.

Analysis of the expression and polymorphism of APOE, HSP, BDNF, and GRIN2B genes associated with the neurodegeneration process in the pathogenesis of primary open angle glaucoma.

Glaucoma is characterized by optic neuropathy of the RGC or retinal nerve fiber. The aim of this study was to evaluate a relationship between the neurodegenerative genes' polymorphisms of the APOE (rs449647), BDNF (rs2030324), GRIN2B (rs3764028), and HSP70-1 (rs1043618) and the occurrence risk of POAG and to investigate its effect on allele-specific gene expression. Genomic DNA was extracted from peripheral blood. Analysis of the genes' polymorphisms was performed using PCR-RFLP. The level of mRNA expression was determined by QRT-PCR. We showed a statistically significant association of BDNF and APOE genes' polymorphisms with a risk of POAG occurrence. There was a statistically significant association of the rs2030324 polymorphism with progression of POAG based on cup disc ratio value and rs1043618 polymorphism based on nerve fiber index and rim area. Furthermore, we found that mean HSP70-1 mRNA expression was significantly lower in the case of individuals with the G/G genotype than in the case of minor allele carriers, that is, G/C and C/C. We also found that BDNF and HSP70-1 expression level are associated with the progression of POAG based on rim area value. In conclusion, our results suggest that BDNF, APOE, and HSP70-1 genes might be associated with a risk of POAG occurrence in the Polish population.

Effects of a Long Term Physical Exercise on the mrna Level of BDNF in Mice after Middle Cerebral Artery Occlusion

Backgroud: BDNF plays an important role in maintaining survival and function of neurons. Exercise may be increasing the mRNA and protein level of BDNF in hippocampus and cortex. Objective: To investigate the impact of a long-term physical training on the mRNA and protein level of BDNF after Middle Cerebral Artery Occlusion (MCAO) in mice. Design, Time and Seting: A randomized, controlled, animal experiment was performed at the department of rehabilitation medicine, Chinese PLA general hospital Materials: Twenty-six male C57 BL/6J mice (20–30g, 2-3 months old) were provided by Experimental Animal Center of Institute of Medicine, Chinese PLA general hospital. Methods: Twenty-six male C57 BL/6J mice underwent MCAO (described by Bederson JB et al) and then were divided into training group Ι (n=9), training group II (n=9) and control group (n=8). The mice of training group I were trained with voluntary running wheel for one hour daily (6 days per week) for 90 days; The mice of training group II were trained for 15 days, stopped for 30 days and retrained for 45 days after MCAO .The running wheel of control group was fixed. The mRNA level of BDNF mice brain was tested by RT-PCR method 90 days after MCAO. The design of study is completely randomized among three groups. Wilcoxon rank sum test and Kruskal-Wallis test were performed. Main Measures: Quantitation of the expression of BDNF genes is determined by RT-PCR for mRNA level techniques and Western blotting for protein level. Results: Both the mRNA and protein levels of BDNF mice brain are significantly higher in training group I and training group II than that in control group in 90 days after MCAOi¼ˆT values respectively are 5.1 and 3.9,P 0.05). Conclusion: The long term physical training can elevate the mRNA and protein levels of BDNF in mice brain after Middle Cerebral Artery Occlusion.

Activation of Schwann cells in vitro by magnetic nanocomposites via applied magnetic field.

Schwann cells (SCs) are attractive seed cells in neural tissue engineering, but their application is limited by attenuated biological activities and impaired functions with aging. Therefore, it is important to explore an approach to enhance the viability and biological properties of SCs. In the present study, a magnetic composite made of magnetically responsive magnetic nanoparticles (MNPs) and a biodegradable chitosan–glycerophosphate polymer were prepared and characterized. It was further explored whether such magnetic nanocomposites via applied magnetic fields would regulate SC biological activities. The magnetization of the magnetic nanocomposite was measured by a vibrating sample magnetometer. The compositional characterization of the magnetic nanocomposite was examined by Fourier-transform infrared and X-ray diffraction. The tolerance of SCs to the magnetic fields was tested by flow-cytometry assay. The proliferation of cells was examined by a 5-ethynyl-2-deoxyuridine-labeling assay, a PrestoBlue assay, and a Live/Dead assay. Messenger ribonucleic acid of BDNF, GDNF, NT-3, and VEGF in SCs was assayed by quantitative real-time polymerase chain reaction. The amount of BDNF, GDNF, NT-3, and VEGF secreted from SCs was determined by enzyme-linked immunosorbent assay. It was found that magnetic nanocomposites containing 10% MNPs showed a cross-section diameter of 32.33±1.81 µm, porosity of 80.41%±0.72%, and magnetization of 5.691 emu/g at 8 kOe. The 10% MNP magnetic nanocomposites were able to support cell adhesion and spreading and further promote proliferation of SCs under magnetic field exposure. Interestingly, a magnetic field applied through the 10% MNP magnetic scaffold significantly increased the gene expression and protein secretion of BDNF, GDNF, NT-3, and VEGF. This work is the first stage in our understanding of how to precisely regulate the viability and biological properties of SCs in tissue-engineering grafts, which combined with additional molecular factors may lead to the development of new nerve grafts.

The mood-stabilizer lithium prevents hippocampal apoptosis and improves spatial memory in experimental meningitis.

Pneumococcal meningitis is associated with high morbidity and mortality rates. Brain damage caused by this disease is characterized by apoptosis in the hippocampal dentate gyrus, a morphological correlate of learning deficits in experimental paradigms. The mood stabilizer lithium has previously been found to attenuate brain damage in ischemic and inflammatory diseases of the brain. An infant rat model of pneumococcal meningitis was used to investigate the neuroprotective and neuroregenerative potential of lithium. To assess an effect on the acute disease, LiCl was administered starting five days prior to intracisternal infection with live Streptococcus pneumoniae. Clinical parameters were recorded, cerebrospinal fluid (CSF) was sampled, and the animals were sacrificed 42 hours after infection to harvest the brain and serum. Cryosections of the brains were stained for Nissl substance to quantify brain injury. Hippocampal gene expression of Bcl-2, Bax, p53, and BDNF was analyzed. Lithium concentrations were measured in serum and CSF. The effect of chronic lithium treatment on spatial memory function and cell survival in the dentate gyrus was evaluated in a Morris water maze and by quantification of BrdU incorporation after LiCl treatment during 3 weeks following infection. In the hippocampus, LiCl significantly reduced apoptosis and gene expression of Bax and p53 while it increased expression of Bcl-2. IL-10, MCP-1, and TNF were significantly increased in animals treated with LiCl compared to NaCl. Chronic LiCl treatment improved spatial memory in infected animals. The mood stabilizer lithium may thus be a therapeutic alternative to attenuate neurofunctional deficits as a result of pneumococcal meningitis.

DNA methylation of BDNF as a biomarker of early-life adversity

Early-life adversity increases the risk for psychopathology in later life. The underlying mechanism(s) is unknown, but epigenetic variation represents a plausible candidate. Early-life exposures can disrupt epigenetic programming in the brain, with lasting consequences for gene expression and behavior. This evidence is primarily derived from animal studies, with limited study in humans due to inaccessibility of the target brain tissue. In humans, although there is evidence for DNA methylation changes in the peripheral blood of psychiatric patients, a fundamental question remains as to whether epigenetic markers in the blood can predict epigenetic changes occurring in the brain. We used in utero bisphenol A (BPA) exposure as a model environmental exposure shown to disrupt neurodevelopment and exert long-term effects on behavior in animals and humans. We show that prenatal BPA induces lasting DNA methylation changes in the transcriptionally relevant region of the Bdnf gene in the hippocampus and blood of BALB/c mice and that these changes are consistent with BDNF changes in the cord blood of humans exposed to high maternal BPA levels in utero. Our data suggest that BDNF DNA methylation in the blood may be used as a predictor of brain BDNF DNA methylation and gene expression as well as behavioral vulnerability induced by early-life environmental exposure. Because BDNF expression and DNA methylation are altered in several psychiatric disorders that are associated with early-life adversity, including depression, schizophrenia, bipolar disorder, and autism, BDNF DNA methylation in the blood may represent a novel biomarker for the early detection of psychopathology.

Expression of VEGF, GFAP, and BDNF genes in the brain of rats after fractionated γ-irradiation according to different protocols.

The expression of VEGF, GFAP, and BDNF genes in the nervous tissue changed on weeks 4, 8, and 12 after fractionated irradiation of the brain according to different protocols in a fixed total dose of 36 Gy. The expression of VEGF gene decreased in the prefrontal cortex and hippocampus after 4 and 8 weeks. After week 12, the expression of VEGF normalized in the prefrontal cortex and remained low in the hippocampus. The expression of GFAP gene was maximum in the prefrontal cortex after week 4 and returned to normal in week 12. In the hippocampus, the expression of GFAP was low only after week 12. The expression of BDNF gene was reduced only during the week 8 and this decrease was directly proportional to the single dose. Hence, fractionated γ-irradiation with fixed total dose differently modified gene expression in the nervous tissue.

The Effects of Suanzaoren decoction on hippocampus, cortex BDNF and TrKB geneexpression in depression rats

Objective To investigate the effect of Suanzaoren Decoction on hippocampus, cortex BDNF and TrKB gene expression in depression model rats. Methods Depression rat models were established by social-isolated raise and chronic stress stimulation. Suanzaoren decoction was administrated to the models. RT-PCR was adopted to detect the expression of mRNA BDNF and TrKB genes. Results The mRNA expression of BDNF and TrKB in cortex of Suanzaoren decoction high dose group、medium dose group and clomipramine group（0.213±0.094, 0.639±0.023, 1.032±0.015, 1.089±0.014, 1.580±0.012, 1.860±0.019）were all higher than the model group（0.032±0.008, 0.001±0.000）, showing a significant difference among four groups （P〈0.01）, and the mRNA expression of BDNF and TrKB in hippocampus of Suanzaoren decoction high dose group, medium dose group and clomipramine group（0.213±0.094, 0.639±0.023, 1.032±0.015, 1.089±0.014, 1.580± 0.012, 1.860±0.019）were higher than the model group （0.021±0.015, 0.125±0.013）, there was a significant difference between four groups（P〈0.01）. Compared with the model group, the mRNA expression of low-dose group of Suanzaoren decoction in both cortex and hippocampus of BDNF and TrKB was not significantly different to the model group（P>0.05）. Conclusion Suanzaoren decoction can increase the expression of BDNF and TrKB gene, promote neuronal proliferation, and resist depression. Key words: Depression; Suanzaoren Decoction; BDNF; TrKB

SUSTAINED DELIVERY OF SURFACE MODIFIED DONEPEZIL HCL LOADED PCL NANOPARTICLES FOR ALZHEIMER'S DISEASE

pathways. Since brain inflammation and hippocampal neurogenesis may correlate with bioenergetic function, we also analyzed genes and proteins that reflect neurogenesis and brain inflammation activity. Results: 21month old C57BL/6 mice showed increased brain PGC-1a protein, mTOR and phospho-mTOR protein, citrate synthase mRNA, and mtDNA copy number. Hippocampal VEGF-A gene expression trended higher, and a positive correlation between VEGF-A and PRC mRNA levels was observed. Brain DCX, BDNF, TNF-a, and CCL11 gene expression, as well as plasma CCL11 protein levels, were unchanged. Despite these apparent negative findings, a negative correlation between plasma CCL11 protein levels and hippocampal DCX gene expression was observed; further analysis indicated exercise may mitigate this relationship. Conclusions: Supra-lactate threshold exercise beneficially impacts bioenergetic-relevant parameters in the brains of aged mice. Our data further suggest supra-lactate threshold exercise may enhance neurogenesis by uncoupling it from the effects of inflammatory chemokines. This study supports the view that exercising above the lactate threshold may benefit the aging brain.

Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury

Previous work from our group has shown that intranasal MSC-treatment decreases lesion volume and improves motor and cognitive behavior after hypoxic–ischemic (HI) brain damage in neonatal mice. Our aim was to determine the kinetics of MSC migration after intranasal administration, and the early effects of MSCs on neurogenic processes and gliosis at the lesion site.HI brain injury was induced in 9-day-old mice and MSCs were administered intranasally at 10days post-HI. The kinetics of MSC migration were investigated by immunofluorescence and MRI analysis. BDNF and NGF gene expression was determined by qPCR analysis following MSC co-culture with HI brain extract. Nestin, Doublecortin, NeuN, GFAP, Iba-1 and M1/M2 phenotypic expression was assessed over time.MRI and immunohistochemistry analyses showed that MSCs reach the lesion site already within 2h after intranasal administration. At 12h after administration the number of MSCs at the lesion site peaks and decreases significantly at 72h. The number of DCX+ cells increased 1 to 3days after MSC administration in the SVZ. At the lesion, GFAP+/nestin+ and DCX+ expression increased 3 to 5days after MSC-treatment. The number of NeuN+ cells increased within 5days, leading to a dramatic regeneration of the somatosensory cortex and hippocampus at 18days after intranasal MSC administration. Interestingly, MSCs expressed significantly more BDNF gene when exposed to HI brain extract in vitro. Furthermore, MSC-treatment resulted in the resolution of the glial scar surrounding the lesion, represented by a decrease in reactive astrocytes and microglia and polarization of microglia towards the M2 phenotype.In view of the current lack of therapeutic strategies, we propose that intranasal MSC administration is a powerful therapeutic option through its functional repair of the lesion represented by regeneration of the cortical and hippocampal structure and decrease of gliosis.

Expression of BDNF gene in the femur of aged vs adult rats

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

Asymmetrical expression of BDNF and NTRK3 genes in frontoparietal cortex of stress-resilient rats in an animal model of depression.

The current study is based on the "approach-withdrawal" theory of emotional regulation and lateralization of brain function in rodents, which has little been studied. The aim was to indentify asymmetry in hemispheric genes expression during depression. Depressive-like symptoms were induced in rats using chronic mild stress protocol. The sucrose consumption test was performed to identify the anhedonic and stress-resilient rats. After decapitation, RNA was extracted from frontotemporal cortex of both hemispheres of anhedonic and stress-resilient rats. The pattern of gene expression in these samples was compared with controls by real-time polymerase chain reaction. A linear mixed model analysis of variance was fitted to the data to estimate the effect of rat line. From the total of 30 rats in the experimental group, five rats were identified to be anhedonic and five were stress-resilient, according to the result of sucrose-consumption test. BDNF and NTRK-3 were expressed at significantly lower levels in the right hemisphere of anhedonic rats compared with stress-resilient rats. No significant difference was found between left hemispheres. Hemispheric asymmetry in the level of gene expression was only observed for the BDNF gene in stress-resilient rats, upregulated in right hemisphere compared with the left. Expression of NTRK3, HTR2A, COMT, and SERT was not lateralized. There was no significant asymmetry between hemispheres of anhedonic rats. This study supports the evidence for the role of genes responsible for neural plasticity in pathophysiology of depression, emphasizing probable hemispheric asymmetry at level of gene expression.

Effects of exercise on mitochondrial function, neuroplasticity and anxio-depressive behavior of mice

The present study was aimed at analyzing the effects of physical exercise on mitochondrial physiology, anxio-depressive-like behaviors and neuroplasticity in mice. Adult C57BL/6J male mice were isolated in home cages equipped or not with free-running wheels. After 6weeks of exercise, mice were tested in various behavioral paradigms to evaluate anxiety- and depressive-like behaviors. The hippocampi were dissected for neurochemical assays, including mitochondrial activity, monoamines content and the expression of genes involved in energy metabolism and brain-derived neurotrophic factor (BDNF) regulation. Exercise decreased anxiety-like behaviors in the open field and elevated plus maze, and exerted antidepressant-like effects in the tail suspension test. Exercise stimulated brain mitochondrial activity and increased resistance against rotenone, an inhibitor of complex I activity. Furthermore, mRNA expression of Bdnf, Gdnf, Tfam (mitochondrial transcription factor A), and Ndufa6 (mitochondrial I subunit) genes, as well as the phosphorylation of cAMP response element-binding protein were increased after exercise. In summary, exercise appears to engage mitochondrial pathways and to potentiate neuroplasticity and might be associated to mood improvement.