Neurotrophic Factor mRNA Expression Research Articles

Regional Changes in Brain Biomolecular Markers in a Collagen-Induced Arthritis Rat Model.

The effects of collagen-induced arthritis (CIA), a model of systemic inflammation, on brain regional molecular markers associated with neurological disorders are uncertain. This study investigated the brain regional molecular changes in markers associated with inflammation and neuronal dysfunction in a CIA model. Fourteen male Sprague Dawley rats were divided into control (n = 5) or CIA (n = 9) groups. 10 weeks after CIA induction, brain tissue was collected. Brain regional mRNA expression of inflammatory markers (IL-1β and IL-6), apoptotic markers (BAX and Bcl2) and neurotrophic factors (BDNF, CREB and TrkB) was determined. Monoamine distribution and abundance in different brain regions were determine by mass spectrometry imaging (MSI). Neuroinflammation was confirmed in the CIA group by increased IL-β mRNA expression, concurrent with an increased BAX/Bcl2 ratio. The mRNA expression of CREB was increased in the midbrain and hippocampus while BDNF was increased and TrkB was decreased across all brain regions in CIA compared to control animals. Serotonin was decreased in the midbrain and hippocampus while dopamine was decreased in the striatum of CIA rats, compared to controls. CIA resulted in neuroinflammation concurrent with an apoptotic state and aberrant expression of neurotrophic factors and monoamines in the brain, suggestive of neurodegeneration.

Early-life manipulation of the serotonergic system exacerbates the harmful effects of sleep deprivation on cognitive functions.

Serotonin is a monoamine neurotransmitter that plays a main role in regulating physiologicaland cognitive functions. Serotonergic system dysfunction is involved in the etiology of various psychiatric and neurological disorders. Therefore, the present study was designed to investigate the effects of early-life serotonin depletion on cognitive disorders caused by sleep deprivation. Serotonin was depleted by para-chlorophenylalanine (PCPA, 100 mg/kg, s.c.) at postnatal days 10-20, followed by sleep deprivation-induced through the multiple platform apparatus for 24 h at PND 60. After the examination of the novel object recognition and passive avoidance memories, the hippocampi and prefrontal cortex were dissected to examine the brain-derived neurotrophic factor (BDNF) mRNA expression by PCR. Our findings showed that postnatal serotonin depletion and sleep deprivation impaired the novel object recognition and passive avoidance memories and changed the BDNF levels. In the same way, the serotonin depletion in early life before sleep deprivation exacerbated the harmful effects of sleep deprivation on cognitive function and BDNF levels. It can be claimed that the serotonergic system plays a main role in the modulation of sleep and cognitive functions.

Ovomemolins: Egg-derived peptides that improved cognitive decline after oral administration in mice.

Eggs not only contain all the molecules necessary to nurture new life but are also rich in nutrients such as high-quality protein. For example, epidemiologic studies have shown that egg intake is positively correlated with cognitive function. Thus, we specifically examined the effect of ovalbumin, a major protein present in egg whites, on cognitive function. First, we found that an orally administered enzymatic digest of ovalbumin improves cognitive function in mice fed a high-fat diet. Then, we narrowed down candidate peptides based on the prediction of peptide production according to enzyme-substrate specificity and comprehensive peptide analysis of the digest. We found that three peptides, namely ILPEY, LYRGGLEP, and ILELP, improve cognitive function after oral administration. We also showed that ILPEY, LYRGGLEP, and ILELP were present in the digest and named them ovomemolins A (OMA), B, and C, respectively. Notably, ovomemolins are the first peptides derived from egg whites that have been shown to improve cognitive function. The cognitive improvement induced by OMA, the most abundant of the peptides in the digest, was inhibited by methyllycaconitine, an antagonist of α7nAChR, which is known to be related to memory. These results suggest that OMA improves cognitive function through the acetylcholine system. After OMA administration, brain-derived neurotrophic factor (BDNF) mRNA expression and the number of 5-bromo-2'-deoxyuridine-positive cells suggested that OMA increases hippocampal BDNF expression and neurogenesis.

Aripiprazole combined with nerve growth factor improves cognitive function in mice with schizophrenia model

The pathogenesis and treatment of cognitive dysfunction in patients with schizophrenia (SCZ) remains a challenge. Exploring new effective treatment strategies is relevant for the improvement of cognitive function. Aripiprazole (ARI) is an atypical antipsychotic that improves some cognitive functions. Nerve growth factor (NGF) has been shown to improve cognitive function in certain neurological impairments and partial neurological deficits, but its mechanism of action in cognitive dysfunction in SCZ is unclear. In this study, we established schizophrenia mouse model with dizocilpine (MK-801); treated mice with ARI alone or in combination with NGF; assessed spontaneous activity and cognitive function using open field test and Morris water maze test; and measured brain-derived neurotrophic factor (BDNF) protein and mRNA expression levels using immunohistochemistry and molecular biology assays. The results showed that ARI alone or in combination with NGF can improve increased spontaneous activity and spatial learning memory deficits in model mice by elevating BDNF expression levels in prefrontal cortex (PFC) and hippocampus (HIP). The results suggest that ARI combined with NGF can improve cognitive function in SCZ, which provides new ideas and directions for the clinical treatment of cognitive dysfunction in SCZ.

Neuroprotective effect of South Sulawesi propolis on neurogenesis in primary cultures of rat cerebral cortical neurons

BackgroundNeurodegenerative diseases have a significant risk factor, namely aging, which is associated with increased neuronal dysfunction and death. Propolis has been widely used as medicine due to its various benefits. This research study investigated the effect of propolis from the stingless bee (Tetragonula sapiens) from South Sulawesi, Indonesia, on neurogenesis in primary cultures of embryonic cerebral cortex of Wistar rats at 17-18 days of gestation. Methods This research was an experimental study involving 4 female pregnant Wistar rats, which were terminated and the cerebral cortex of the embryos collected and grown as primary cultures. The cultures were divided into 3 groups, i.e. control, vehicle, and propolis extract group. The research began with 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) to obtain the optimal dose among propolis doses of 0.5 μg/mL, 1 μg/mL, 5 μg/mL, 10 μg/mL, 25 μg/mL, and 100 μg/mL. The study was continued by using the best dose in immunostaining examination using microtubule-associated protein 2 (MAP2) primary antibody and qRT-PCR examination of brain-derived neurotrophic factor (BDNF) mRNA expression. One Way ANOVA and Kruskal-Wallis test were used to analyse the data. ResultsThe results showed that the propolis doses of 0.5 μg/mL and 1 μg/mL significantly increase cell viability compared to the other doses (p=0.011) and stimulate dendritic growth. The propolis dose group of 1 μg/mL induces a significantly higher expression of BDNF mRNA than the control group (p=0.031). ConclusionOur findings indicate that stingless bee propolis has neuroprotective effects against BDNF mRNA in rats. It is shown that propolis can be a candidate inhibitor in neurodegenerative diseases.

Novel neuron-Schwann cell co-culture models to study peripheral nerve degeneration and regeneration.

Novel neuron-Schwann cell co-culture models to study peripheral nerve degeneration and regeneration.

Ultrasound Therapy of Injury Site Modulates Gene and Protein Expressions in the Dorsal Root Ganglion in a Sciatic Nerve Crush Injury Rat Model.

The aim of this study was to verify the effects of ultrasound on dorsal root ganglion (DRG) neurons at the injury site in a rat model of sciatic nerve crush injury. We evaluated the mRNA expression of neurotrophic and pro-inflammatory factors by quantitative reverse transcription polymerase chain reaction 7 and 14 d post-injury. We also evaluated the protein levels of brain-derived neurotrophic factor (BDNF) 7 and 14 d post-injury. Axon regeneration and motor function analyses were performed 21 days after injury to confirm the facilitative effect of ultrasound on nerve regeneration. In the ultrasound group, BDNF and interleukin-6 mRNA expression of the DRG was significantly reduced 7 d post-injury. Compared with the sham group, the BDNF protein expression of the DRG in the ultrasound group remained at a higher level 14 d post-injury. Motor function, myelinated fiber density and myelin sheath thickness were significantly higher in the ultrasound group than in the sham group 21 d post-injury. These results indicate that ultrasound therapy at the injury site promotes nerve regeneration and modulates gene and protein expression in the DRG of a rat model of a sciatic nerve crush injury.

Alleviation of Cognitive and Physical Fatigue with Enzymatic Porcine Placenta Hydrolysate Intake through Reducing Oxidative Stress and Inflammation in Intensely Exercised Rats.

Intense exercise is reported to induce physical and cognitive fatigue, but few studies have focused on treatments to alleviate fatigue. We hypothesized that the oral supplementation of enzymatic porcine placenta hydrolysate (EPPH) prepared using protease enzymes could alleviate exercise-induced fatigue in an animal model. The objectives of the study were to examine the hypothesis and the action mechanism of EPPH in relieving physical and cognitive fatigue. Fifty male Sprague-Dawley rats aged 8 weeks (body weight: 201 g) were classified into five groups, and rats in each group were given oral distilled water, EPPH (5 mg nitrogen/mL) at doses of 0.08, 0.16, or 0.31 mL/kg body weight (BW)/day, or glutathione (100 mg/kg BW/day) by a feeding needle for 5 weeks, which were named as the control, L-EPPH, M-EPPH, H-EPPH, or positive-control groups, respectively. Ten additional rats had no intense exercise with water administration and were designated as the no-exercise group. After 2 weeks, the rats were subjected to intense exercise and forced swimming trial for 30 min once per week for an additional 4 weeks. At 5 min after the intense exercise, lactate concentrations and lactate dehydrogenase (LDH) activity in the serum and the gastrocnemius muscle were higher in the control group, whereas M-EPPH and H-EPPH treatments suppressed the increase better than in the positive-control (p < 0.05). Intense exercise decreased glycogen content in the liver and gastrocnemius muscle, and M-EPPH and H-EPPH inhibited the decrement (p < 0.05). Moreover, lipid peroxide contents in the gastrocnemius muscle and liver were higher in the control group than in the M-EPPH, H-EPPH, positive-control, and no-exercise groups (p < 0.05). However, antioxidant enzyme activities such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were opposite to the lipid peroxide contents. Hypothalamic corticosterone and hippocampal mRNA expressions of tumor necrosis factor (TNF)-α and IL-1β were higher. However, hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression and protein contents were lower in the control group than in the positive-control group. M-EPPH, H-EPPH, and positive-control suppressed the changes via activating hippocampal cAMP response element-binding protein phosphorylation, and H-EPPH showed better activity than in the positive-control (p < 0.05). In conclusion, EPPH (0.16-0.31 mL/kg BW) intake reduced exercise-induced physical and cognitive fatigue in rats and could potentially be developed as a therapeutic agent for relieving fatigue in humans.

Beneficial effects of enriched environment on behavior, cognitive functions, and hippocampal brain-derived neurotrophic factor level following postnatal serotonin depletion in male rats.

The neurotransmitter serotonin (5-HT) is one of the most important modulators of neural circuitry and has a critical role in neural development and functions. Previous studies indicated that changes in serotonergic system signaling in early life critically impact mental health, behavior, the morphology of hippocampal neurons, and cognitive functions across the lifespan. The enriched environment (EE) has indicated beneficial effects on behavior and cognitive functions in the developmental period of life, but its impacts on cognitive impairments and behavioral changes following postnatal serotonin depletion are unknown. Therefore, the present study aimed to evaluate the influences of the EE housing (postnatal days [PNDs] 21-60) following postnatal serotonin depletion (by para-chlorophenylalanine [PCPA], 100 mg/kg, s.c, in PNDs 10-20) on anxiety-related behaviors, cognitive functions, and brain-derived neurotrophic factor (BDNF) mRNA expression in the hippocampus of male rats. Memory and behavioral parameters were examined in early adulthood and after that, the hippocampi of rats were removed to determine the BDNF mRNA expression by PCR (PNDs 60-70). The findings of the present work indicated that adolescent EE exposure alleviated memory impairment, decreased BDNF levels, and anxiety disorders induced by experimental depletion of serotonin. Overall, these results indicate that serotonergic system dysregulation during the developmental periods can be alleviated by adolescent EE exposure.

Brain fractalkine-CX3CR1 signalling is anti-obesity system as anorexigenic and anti-inflammatory actions in diet-induced obese mice

Fractalkine is one of the CX3C chemokine family, and it is widely expressed in the brain including the hypothalamus. In the brain, fractalkine is expressed in neurons and binds to a CX3C chemokine receptor 1 (CX3CR1) in microglia. The hypothalamus regulates energy homeostasis of which dysregulation is associated with obesity. Therefore, we examined whether fractalkine-CX3CR1 signalling involved in regulating food intake and hypothalamic inflammation associated with obesity pathogenesis. In the present study, fractalkine significantly reduced food intake induced by several experimental stimuli and significantly increased brain-derived neurotrophic factor (BDNF) mRNA expression in the hypothalamus. Moreover, tyrosine receptor kinase B (TrkB) antagonist impaired fractalkine-induced anorexigenic actions. In addition, compared with wild-type mice, CX3CR1-deficient mice showed a significant increase in food intake and a significant decrease in BDNF mRNA expression in the hypothalamus. Mice fed a high-fat diet (HFD) for 16 weeks showed hypothalamic inflammation and reduced fractalkine mRNA expression in the hypothalamus. Intracerebroventricular administration of fractalkine significantly suppressed HFD-induced hypothalamic inflammation in mice. HFD intake for 4 weeks caused hypothalamic inflammation in CX3CR1-deficient mice, but not in wild-type mice. These findings suggest that fractalkine-CX3CR1 signalling induces anorexigenic actions via activation of the BDNF-TrkB pathway and suppresses HFD-induced hypothalamic inflammation in mice.

A Dietary Supplement Containing Micronutrients, Phosphatidylserine, and Docosahexaenoic Acid Counteracts Cognitive Impairment in D-Galactose-Induced Aged Rats.

At present, it is a trend to use dietary supplements to prevent age-related cognitive impairment. This study aimed to investigate the effects of a dietary supplement enriched with micronutrients, phosphatidylserine, and docosahexaenoic acid on cognitive performance using a D-galactose (D-gal) induced aging rat model. Seven-month-old male Sprague-Dawley rats were randomly divided into five groups, including the control group, D-gal model group, and low-dose (2 g/kg body weight), medium-dose (6 g/kg body weight), and high-dose (10 g/kg body weight) dietary supplement intervention groups, which were investigated for 13 weeks. The dietary supplement intervention was found to improve cognitive performance in Morris water maze test, increase superoxidase dismutase activity, reduce malondialdehyde activity, decrease tumor necrosis factor-α and interleukin-6 concentrations, inhibit the activation of astrocytes, and elevate brain-derived neurotrophic factor protein and mRNA expression in the brains of D-gal-induced aged rats. This dietary supplement customized for the aged can be applied to the restoration of cognitive performance by enhancing antioxidant and anti-neuroinflammatory abilities, up-regulating neurotrophic factors, and inhibiting the activation of astrocytes. These results will be useful for future studies focused on implementation in humans.

Antidepressant effects of acupuncture in a murine model: regulation of neurotrophic factors.

GV20 and Yintang are important targets in acupuncture treatment for depression. In this study, we examined the antidepressant effects of simultaneous acupuncture stimulation at GV20 and Yintang. We compared the antidepressant effects of manual acupuncture (MA) stimulation at GV20 and Yintang, compared to acupuncture stimulation at two control point locations on the back of the mice (overlying the spinal column) and imipramine administration in a forced swimming (FS)-induced mouse model of depression, and examined the mRNA and protein expression of neurotrophic factors, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin (NT)-3, and NT-4/5 in the brains by real-time polymerase chain reaction in two different experimental schedules - preventive (MA given alongside FS modelling) and therapeutic (MA given after FS-induced depression was already established). MA at GV20 and Yintang significantly reduced the immobility time of mice with FS-induced depression in both preventive and therapeutic experimental designs, with effects that were comparable to those of imipramine administration. Immobility time following simultaneous acupuncture stimulation of the two control point locations overlying the spinal column was significantly suppressed only 2 weeks after the start of FS in the preventive effect experiment, and the suppressive effect was significantly lower than that of simultaneous acupuncture stimulation at GV20 and Yintang. In the therapeutic effect experiment, there was no change in the increase in immobility time after the end of FS. MA at GV20 and Yintang significantly increased the expression of BDNF and NT-3 in the preventive evaluation and NGF, BDNF, NT-3, and NT-4/5 in the therapeutic effect evaluation. Our findings suggest that simultaneous acupuncture stimulation at GV20 and Yintang is effective for the prevention and treatment of depression, and the effect likely involves modulation of the expression of multiple neurotrophic factors.

The Anxiolytic-Like Effects of Protocatechuic Acid in an Animal Model of Post-Traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is a serious psychiatric disorder characterized by impaired fear extinction, depression, and anxiety caused by dysregulation of the hypothalamic-pituitary-adrenal axis and an imbalance of monoamines. Protocatechuic acid (PCA; 3,4-dihydroxybenzoic acid), a major polyphenol metabolite, has various pharmacological effects, such as anti-inflammatory, antioxidant, anti-apoptotic, and neuroprotective activities. In this study, the efficacy of PCA for fear extinction, antidepressant, and anxiolytic effects in PTSD-mediated psychiatric disorders, were evaluated by exposing rats to single prolonged stress (SPS). Male rats were administered PCA (100 or 200 mg/kg) once daily for 14 days after exposure to SPS. PCA significantly decreased situational fear, depressive and anxiety-like behaviors, and corticosterone levels. In addition, PCA regulated the imbalance of serotonin and norepinephrine in the fear circuit region (i.e., the medial prefrontal cortex and hippocampus [Hipp]), and suppressed the decrease in brain-derived neurotrophic factor mRNA expression in the Hipp. The results showed that PCA administration improves freezing behavior and has antidepressant and anti-anxiety effects through modulation of the serotonergic nervous system and monoamines in rats. These results indicated that PCA may be useful as a food ingredient to prevent PTSD.

Cnestis ferruginea Vahl ex DC (Connaraceae) downregulates expression of immediate early genes in kainic acid-induced temporal lobe epilepsy in mice.

This study investigates the influence of Cnestis ferruginea (CF) on kainic acid (KA)-induced immediate early genes (IEGs) associated with hippocampal sclerosis in temporal lobe epilepsy (TLE) in mice. Animals were randomly divided into preventive treatment; vehicle (10mL/kg, p.o.) or CF (400mg/kg, p.o.) for three consecutive days before KA (5mg/kg, i.p.) on days 4 and 5. In the reversal model, KA (5mg/kg, i.p.) was administered on days 1 and 2 before CF (400mg/kg) administration on days 3-5. Animals were euthanized on day 5, 6h after KA exposure in preventive model and 1h after CF administration in reversal model to estimate markers of IEGs. KA upregulated the expression of c-Fos protein by 3.32-, 9.45-, 8.13-, and 8.66-fold in the hippocampal CA1, CA2, CA3, and DG regions, respectively. Also, KA elevated inducible nitric oxide synthase protein expression by 10.9-, 10.6-, 9.78-, and 9.51-fold. Besides, mRNA expression of brain-derived neurotrophic factors and heat shock protein was increased by 2.38- and 1.39-fold, respectively, after exposure to KA which were attenuated by CF. CF attenuated KA-induced IEGs and could be used as an adjunct in TLE.

Neuroplastic Changes in the Superior Colliculus and Hippocampus in Self-rewarding Paradigm: Importance of Visual Cues.

Coincident excitation via different sensory modalities encoding objects of positive salience is known to facilitate learning and memory. With a view to dissect the contribution of visual cues in inducing adaptive neural changes, we monitored the lever press activity of a rat conditioned to self-administer sweet food pellets in the presence/absence of light cues. Application of light cues facilitated learning and consolidation of long-term memory. The superior colliculus (SC) of rats trained on light cue showed increased neuronal activity, dendritic branching, and brain-derived neurotrophic factor (BDNF) protein and mRNA expression. Concomitantly, the hippocampus showed augmented neurogenesis as well as BDNF protein and mRNA expression. While intra-SC administration of U0126 (inhibitor of ERK 1/2 and long-term memory) impaired memory formation, lidocaine (local anaesthetic) hindered memory recall. The light cue-dependent sweet food pellet self-administration was coupled with increased efflux of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens shell (AcbSh). In conditioned rats, pharmacological inhibition of glutamatergic signalling in dentate gyrus (DG) reduced lever press activity, as well as DA and DOPAC secretion in the AcbSh. We suggest that the neuroplastic changes in the SC and hippocampus might represent memory engrams sculpted by visual cues encoding reward information.

Repeated co-treatment with mirtazapine and aripiprazole reversed the schizophrenia-like behaviors and increased the brain-derived neurotrophic factor mRNA expression in the adult Sprague-Dawley rats exposed to glutathione deficit during early postnatal brain development.

Recent studies suggest that impaired glutathione synthesis and dopaminergic transmission are important factors in the pathophysiology of schizophrenia. Moreover, some studies have suggested that antidepressants are able to increase the activity of atypical antipsychotics which may efficiently improve the treatment of negative and some cognitive symptoms of schizophrenia. In the present study, we investigated the influence of repeated co-treated with mirtazapine and aripiprazole on the schizophrenia-like behavior and brain-derived neurotrophic factor (BDNF) mRNA expression in adult rats exposed to glutathione deficit during early postnatal development. Between the postnatal days p5-p16, male pups were treated with the inhibitor of glutathione synthesis, BSO (L-buthionine-(S,R)-sulfoximine) and the dopamine uptake inhibitor, GBR 12909 alone or in combination. Mirtazapine and aripiprazole were given repeatedly, once daily for 21 days before the tests. The behavioral and biochemical tests were performed in p90-92 rats. BSO given alone and in combination with GBR 12909 induced deficits in the studied behavioral tests and decreased the expression of BDNF mRNA. Repeated aripiprazole administration at a higher dose reversed these behavioral deficits. Co-treatment with an ineffective dose of aripiprazole and mirtazapine also abolished the behavioral deficits and biochemical changes, especially in the hippocampus in these rats. The present study indicated that the inhibition of glutathione synthesis in early postnatal development induced long-term deficits corresponding to schizophrenia-like behavior and decreased the BDNF mRNA expression in adult rats, and these behavioural and biochemical deficits were reversed by repeated treatment with a higher dose of aripiprazole and also by co-treatment with an ineffective dose of aripiprazole and mirtazapine. The above data suggest that this neurodevelopment rat model of schizophrenia-induced by glutathione deficit evoked by repeated treatment with BSO alone and together with GBR 12909 in early postnatal life may be useful for studies on the pathomechanism of schizophrenia.

Exercise-Induced Lactate Release Mediates Mitochondrial Biogenesis in the Hippocampus of Mice via Monocarboxylate Transporters.

Regular exercise training induces mitochondrial biogenesis in the brain via activation of peroxisome proliferator-activated receptor gamma-coactivator 1α (PGC-1α). However, it remains unclear whether a single bout of exercise would increase mitochondrial biogenesis in the brain. Therefore, we first investigated whether mitochondrial biogenesis in the hippocampus is affected by a single bout of exercise in mice. A single bout of high-intensity exercise, but not low- or moderate-intensity, increased hippocampal PGC-1α mRNA and mitochondrial DNA (mtDNA) copy number at 12 and 48h. These results depended on exercise intensity, and blood lactate levels observed immediately after exercise. As lactate induces mitochondrial biogenesis in the brain, we examined the effects of acute lactate administration on blood and hippocampal extracellular lactate concentration by in vivo microdialysis. Intraperitoneal (I.P.) lactate injection increased hippocampal extracellular lactate concentration to the same as blood lactate level, promoting PGC-1α mRNA expression in the hippocampus. However, this was suppressed by administering UK5099, a lactate transporter inhibitor, before lactate injection. I.P. UK5099 administration did not affect running performance and blood lactate concentration immediately after exercise but attenuated exercise-induced hippocampal PGC-1α mRNA and mtDNA copy number. In addition, hippocampal monocarboxylate transporters (MCT)1, MCT2, and brain-derived neurotrophic factor (BDNF) mRNA expression, except MCT4, also increased after high-intensity exercise, which was abolished by UK5099 administration. Further, injection of 1,4-dideoxy-1,4-imino-D-arabinitol (glycogen phosphorylase inhibitor) into the hippocampus before high-intensity exercise suppressed glycogen consumption during exercise, but hippocampal lactate, PGC-1α, MCT1, and MCT2 mRNA concentrations were not altered after exercise. These results indicate that the increased blood lactate released from skeletal muscle may induce hippocampal mitochondrial biogenesis and BDNF expression by inducing MCT expression in mice, especially during short-term high-intensity exercise. Thus, a single bout of exercise above the lactate threshold could provide an effective strategy for increasing mitochondrial biogenesis in the hippocampus.

Interleukin-17A regulates ependymal cell proliferation and functional recovery after spinal cord injury in mice

Ependymal cells have been suggested to act as neural stem cells and exert beneficial effects after spinal cord injury (SCI). However, the molecular mechanism underlying ependymal cell regulation after SCI remains unknown. To examine the possible effect of IL-17A on ependymal cell proliferation after SCI, we locally administrated IL-17A neutralizing antibody to the injured spinal cord of a contusion SCI mouse model, and revealed that IL-17A neutralization promoted ependymal cell proliferation, which was paralleled by functional recovery and axonal reorganization of both the corticospinal tract and the raphespinal tract. Further, to test whether ependymal cell-specific manipulation of IL-17A signaling is enough to affect the outcomes of SCI, we generated ependymal cell-specific conditional IL-17RA-knockout mice and analyzed their anatomical and functional response to SCI. As a result, conditional knockout of IL-17RA in ependymal cells enhanced both axonal growth and functional recovery, accompanied by an increase in mRNA expression of neurotrophic factors. Thus, Ependymal cells may enhance the regenerative process partially by secreting neurotrophic factors, and IL-17A stimulation negatively regulates this beneficial effect. Molecular manipulation of ependymal cells might be a viable strategy for improving functional recovery.

Merging the Multi-Target Effects of Kleeb Bua Daeng, a Thai Traditional Herbal Formula in Unpredictable Chronic Mild Stress-Induced Depression.

Major depressive disorder (MDD) is a common and debilitating psychiatric disease characterized by persistent low mood, lack of energy, hypoactivity, anhedonia, decreased libido, and impaired cognitive and social functions. However, the multifactorial etiology of MDD remains largely unknown due the complex interaction between genetics and environment involved. Kleeb Bua Daeng (KBD) is a Thai traditional herbal formula that has been used to promote brain health. It consists of a 1:1:1 ratio of the aerial part of Centella asiatica, Piper nigrum fruit, and the petals of Nelumbo nucifera. According to the pharmacological activities of the individual medicinal plants, KBD has good potential as a treatment for MDD. The present study investigated the antidepressant activity of KBD in an unpredictable chronic mild stress (UCMS) mouse model. Daily administration of KBD to UCMS mice ameliorated both anhedonia, by increasing 2% sucrose intake, and hopeless behavior, by reducing immobility times in the forced swimming test (FST) and tail suspension test (TST) without any effect on locomotor activity. The mechanism of KBD activity was multi-modal. KBD promoted neurogenesis by upregulation of brain-derived neurotrophic factor (BDNF) and cyclic AMP-responsive element binding (CREB) mRNA expression in the frontal cortex and hippocampus. Daily treatment with KBD significantly reversed UCMS-induced HPA axis dysregulation by upregulating the glucocorticoid receptor (GR) while downregulating serum- and glucocorticoid-inducible kinase 1 (SGK1) and FK506 binding protein 5 (FKBP5) mRNA expression. KBD treatment also normalized proinflammatory cytokine expression including tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-1β and IL-6. KBD and its component extracts also exhibited an inhibitory effect in vitro on monoamine oxidase (MAO) A and B. The multiple antidepressant actions of KBD emphasize its potential as an effective, novel treatment for MDD.

Serotonin depletion during the postnatal developmental period causes behavioral and cognitive alterations and decreases BDNF level in the brain of rats.

A survey of the literature indicates that the developmental disruptions in serotonin (5-HT) levels can influence the brain development and the function. To the best of our knowledge, so far, there are a few studies about the effects of developmental period 5-HT depletion on cognition and behavior of adult male and female rats. Therefore, in the present study, we examined the effects of postnatal days (PND 10-20) administration of para-chlorophenylalanine (PCPA, 100mg/kg, s.c) a 5-HT synthesis inhibitor, on anxiety-related behaviors, pain sensitivity, short-term recognition memory, and hippocampal and prefrontal cortex (PFC) brain-derived neurotrophic factor (BDNF) mRNA expression in adult male and female rats. Novel object recognition memory (NORM) and behavioral parameters (anxiety-like behaviors and pain sensitivity) were evaluated in early adulthood and after that, the hippocampi and PFC of the rat's brain were removed for the determination of BDNF mRNA expression. Our results indicated that the postnatal period administration of PCPA impaired short-term NORM. The postnatal developmental period treatment with PCPA also increased anxiety-like behaviors in the open field and elevated plus maze (EPM) tests. Postnatal PCPA treatment increased pain sensitivity in the hot plate test in both male and female rats, especially in female animals. In addition, postnatal days serotonin depletion decreased BDNF level in the hippocampus and PFC of both male and female rats. These findings demonstrate that serotonin plays the main role in neurodevelopment, cognitive functions, and behavior. Therefore, serotonergic system dysregulation during the developmental periods may have more adverse influences on the brain development of rats.