The basal ganglia, a group of nuclei, are associated with a variety of functions, including motor control. The striatum, which is the major input station of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. The striatum is made up 96% of medium spiny neurons which are GABAergic cells. GABAergic cells are known to contain DA receptors which divide into two main branches- the D1 receptor (D1R)-expressing direct pathway and the D2 receptor (D2R)-expressing indirect pathway. The role of these two efferent pathways has not been clear in control of motor behaviors. To establish the influence of the different DA subtypes on GABAergic systems in the striatum, D1 selective receptor agonist (SKF 38393) and D2 selective receptor agonist (Quinpirole) were administered to mice. SKF 38393 and quinpirole were administered intraperitoneally in a volume of 0, 1, 5, 10 (mg/kg) and motor activity was assessed for 60 min immediately after the injection of DA agonists. Mice were sacrificed after behavioral test and the striatum in the brain were dissected for analysis of GABA level with HPLC. Both SKF 38393 and quinpirole dose-dependently increased locomotor activity but, GABA level in the striatum was clearly different in two agonists. These findings provide insight into the selective contributions of the direct and indirect pathways to striatal GABAergic motor behaviors.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine ; Animals ; Basal Ganglia ; Brain ; Chromatography, High Pressure Liquid ; Efferent Pathways ; gamma-Aminobutyric Acid ; Mice ; Motor Activity ; Neurons ; Quinpirole ; Substantia Nigra

The anti-allodynic effect of NMDA receptor antagonist and acupuncture treatments were explored through spinal p35 regulation of diabetic neuropathic rat. We evaluated the change over time of p35/p25 protein levels in the spinal cord compared with behavioral responses to thermal and mechanical stimulation in streptozotocin (STZ)-induced diabetic rats. Additionally, we studied p35 expression when electroacupuncture (EA) and a sub-effective dose of NMDA (N-methyl-D-aspartate) receptor antagonist (MK-801) were used to treat hyperalgesia in the diabetic neuropathic pain (DNP). Thermal paw withdrawal latency (PWL) and mechanical paw withdrawal threshold (PWT) were significantly decreased in the early stage of diabetes in rats. p35 expression after STZ injection gradually decreased from 1 week to 4 weeks compared to normal controls. p25 expression in 4-week diabetic rats was significantly higher than that of 2-week diabetic rats, and thermal PWL in 4-week diabetic rats showed delayed responses to painful thermal stimulation compared with those at 2 weeks. EA applied to the SP-9 point (2 Hz frequency) significantly prevented the thermal and mechanical hyperalgesia in the DNP rat. Additionally, EA combined with MK-801 prolonged anti-hyperalgesia, increased p35 expression, and decreased the cleavage of p35 to p25 during diabetic neuropathic pain. In this study we show EA combined with a sub-effective dose of MK-801 treatment in DNP induced by STZ that is related to p35/p25 expression in spinal cord.
Acupuncture ; Animals ; Diabetic Neuropathies ; Dizocilpine Maleate ; Electroacupuncture ; Hyperalgesia ; N-Methylaspartate ; Neuralgia ; Rats ; Spinal Cord ; Streptozocin

In order to the neuroprotective effect of Lycium chinense fruit (LCF), the present study examined the effects of Lycium chinense fruit on learning and memory in Morris water maze task and the choline acetyltransferase (ChAT) and cyclic adenosine monophosphate (cAMP) of rats with trimethyltin (TMT)-induced neuronal and cognitive impairments. The rats were randomly divided into the following groups: naive rat (Normal), TMT injection+saline administered rat (control) and TMT injection+LCF administered rat (LCF). Rats were administered with saline or LCF (100 mg/kg, p.o.) daily for 2 weeks, followed by their training to the tasks. In the water maze test, the animals were trained to find a platform in a fixed position during 6d and then received 60s probe trial on the 7th day following removal of platform from the pool. Rats with TMT injection showed impaired learning and memory of the tasks and treatment with LCF (p<0.01) produced a significant improvement in escape latency to find the platform in the Morris water maze at the 2nd day. Consistent with behavioral data, treatment with LCF also slightly reduced the loss of ChAT and cAMP in the hippocampus compared to the control group. These results demonstrated that LCF has a protective effect against TMT-induced neuronal and cognitive impairments. The present study suggests that LCF might be useful in the treatment of TMT-induced learning and memory deficit.
Adenosine Monophosphate ; Animals ; Choline O-Acetyltransferase ; Fruit ; Hippocampus ; Learning ; Lycium ; Memory ; Memory Disorders ; Neurons ; Neuroprotective Agents ; Rats ; Trimethyltin Compounds ; United Nations ; Water

We previously demonstrated that repeated exposure to extremely low frequency magnetic fields (ELF-MF) increases locomotor activity via stimulation of dopaminergic D1 receptor (J. Pharmacol. Sci., 2007;105:367-371). Since it has been demonstrated that activator protein-1 (AP-1) transcription factors, especially 35-kDa fos-related antigen (FRA), play a key role in the neuronal and behavioral adaptation in response to various stimuli, we examined whether repeated ELF-MF exposure induces FRA-immunoreactivity (FRA-IR) in the striatum and nucleus accumbens (striatal complex) of the mice. Repeated exposure to ELF-MF (0.3 or 2.4 mT, 1 h/day, for consecutive fourteen days) significantly induced hyperlocomotor activity and FRA-IR in the striatal complex in a field intensity-dependent manner. ELF-MF-induced FRA-IR lasted for at least 1 year, while locomotor activity returned near control level 3 months after the final exposure to ELF-MF. Pretreatment with SCH23390, a dopaminergic D1 receptor antagonist, but not with sulpiride, a dopaminergic D2 receptor antagonist, significantly attenuated hyperlocomotor activity and FRA-IR induced by ELF-MF. Our results suggest that repeated exposure to ELF-MF leads to prolonged locomotor stimulation and long-term expression of FRA in the striatal complex of the mice via stimulation of dopaminergic D1 receptor.
Animals ; Benzazepines ; Magnetic Fields ; Magnetics ; Magnets ; Mice ; Motor Activity ; Neurons ; Nucleus Accumbens ; Sulpiride ; Transcription Factor AP-1 ; Transcription Factors

Neural tissue is arisen from presumptive ectoderm via inhibition of bone morphogenetic protein (BMP) signaling during Xenopus early development. Previous studies demonstrate that ectopic expression of dominant negative BMP4 receptor (DNBR) produces neural tissue in animal cap explants (AC) and also increases the expression level of various genes involved in neurogenesis. To investigate detail mechanism of neurogenesis in transcriptional level, we analyzed RNAs increased by DNBR using total RNA sequencing analysis and identified several candidate genes. Among them, xCITED2 (Xenopus CBP/p300-interacting transcription activator) was induced 4.6 fold by DNBR and preferentially expressed in neural tissues at tadpole stage. Ectopic expression of xCITED2 induced anterior neural genes without mesoderm induction and reduced BMP downstream genes, an eye specific marker and posterior neural marker. Taken together, these results suggest that xCITED2 may have a role in the differentiation of anterior neural tissue during Xenopus early development.
Animals ; Bone Morphogenetic Proteins ; Ectoderm ; Embryonic Structures ; Eye ; Larva ; Mesoderm ; Neurogenesis ; RNA ; Sequence Analysis, RNA ; Xenopus

Neuregulin 1 (NRG1) is associated with the pathogenesis of schizophrenia through controlling activation and signaling of neurotransmitter receptors. Influence to schizophrenia development by the NRG1 gene may differ in individuals, and genetic polymorphism is one of the factors affecting their differences. Association between three single nucleotide polymorphisms (SNPs) (rs7014762, -1174 A/T; rs11998176, -788 A/T; rs3924999, Arg253Gln) of NRG1 and the development of schizophrenia was analyzed in 221 schizophrneia and 359 control subjects. Polymerase chain reaction and direct sequencing were performed to obtain genotype data of NRG1 SNPs of the subjects. In analysis of genetic data, multiple logistic regression models (codominant1, codominant2, dominant, recessive, and log-additive model) were applied. SNPStats and SPSS 18.0 were used to calculate odds ratio (OR), 95% confidence interval (CI), and p-value of each model. The genotype distributions of rs3924999 were associated with schizophrenia development (OR=0.67, 95% CI=0.47-0.95, p=0.022 in the dominant model and OR=0.69, 95% CI=0.51-0.93, p=0.013 in the log-addtive model) and allelic distributions also showed significant association (OR=0.70, 95% CI=0.52-0.93, p=0.014). The results suggest that rs3924999 of the NRG1 gene may be associated with schizophrenia susceptibility.
Genotype ; Logistic Models ; Neuregulin-1 ; Odds Ratio ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Receptors, Neurotransmitter ; Schizophrenia

Microglia are recognized as residential macrophageal cells in the brain. Activated microglia play a critical role in removal of dead or damaged cells through phagocytosis activity. During phagocytosis, however, microglia should survive under the harmful condition of self-producing ROS and pro-inflammatory mediators. TGF-beta has been known as a classic anti-inflammatory cytokine and controls both initiation and resolution of inflammation by counter-acting inflammatory cytokines. In the present study, to understand the self-protective mechanism, we studied time-dependent change of TNF-alpha and TGF-beta production in microglia phagocytizing opsonized-beads (i.e., polystyrene microspheres). We found that microglia phagocytized opsonized-bead in a time-dependent manner and simultaneously produced both TNF-alpha and TGF-beta. However, while TNF-alpha production gradually decreased after 6 h, TGF-beta production remained at increased level. Microglial cells pre-treated with lipopolysaccharides (a strong immunostimulant, LPS) synergistically increased the production of TNF-alpha and TGF-beta both. However, LPS-pretreated microglia produced TNF-alpha in a more sustained manner and became more vulnerable, probably due to the marked and sustained production of TNF-alpha and reduced TGF-beta. Intracellular oxidative stress appears to change in parallel with the microglial production of TNF-alpha. These results indicate TGF-beta contributes for the survival of phagocytizing microglia through autocrine suppression of TNF-alpha production and oxidative stress.
Brain ; Cytokines ; Inflammation ; Lipopolysaccharides ; Microglia ; Oxidative Stress ; Phagocytosis ; Polystyrenes ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha

The purpose of this study was to review potential, physiological, hormonal and neuronal mechanisms that may mediate the sleep changes. This paper investigates the literatures regarding the activity of the hypothalamic-pituitary-adrenal (HPA) axis, one of the main neuroendocrine stress systems during sleep in order to identify relations between stress and sleep disorder and the treatment of stress-induced insomnia. Sleep and wakefulness are regulated by the aminergic, cholinergic brainstem and hypothalamic systems. Activation of the HPA and/or the sympathetic nervous systems results in wakefulness and these hormones including corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol or corticosterone, noradrenaline, and adrenaline, are associated with attention and arousal. Stress-related insomnia leads to a vicious circle by activating the HPA system. An awareness of the close interaction between sleep and stress systems is emerging and the hypothalamus is now recognized as a key center for sleep regulation, with hypothalamic neurontransmitter systems providing the framework for therapeutic advances. An updated understanding of these systems may allow researchers to elucidate neural mechanisms of sleep disorder and to develop effective intervention for sleep disorder.
Adrenocorticotropic Hormone ; Arousal ; Brain Stem ; Corticosterone ; Corticotropin-Releasing Hormone ; Epinephrine ; Hydrocortisone ; Hypothalamus ; Neurons ; Norepinephrine ; Sleep Initiation and Maintenance Disorders ; Sympathetic Nervous System ; Wakefulness ; Axis, Cervical Vertebra ; Sleep Wake Disorders

cAMP response element-binding protein (CREB), a transcription factor, has been shown to play a central role in memory formation, and its involvement in this process has been investigated using a wide range of animal models, from nematodes to higher animals. Various CREB mutant mice have been developed and investigated. Several types of mutant mice with loss of CREB function have impaired memory formation and long-term potentiation (LTP), suggesting that CREB plays essential roles in these processes. To characterize the roles of CREB in memory formation and LTP further, mutant mice displaying gain of CREB function have been generated and analyzed. Importantly, CREB-DIEDML mice and CREB-Y134F mice showed enhanced memory formation, whereas CREB-VP16 mice displayed a lowered threshold of long-lasting LTP (L-LTP) induction, strongly suggesting that CREB functions as a positive regulator of memory formation and LTP. In this review, I focus on the effects of the genetic activation of CREB in LTP and memory formation and summarize previous findings.
Animals ; Brain-Derived Neurotrophic Factor ; Cyclic AMP Response Element-Binding Protein ; Long-Term Potentiation ; Memory ; Mice ; Models, Animal ; Transcription Factors

People experience the feeling of the missing body part long after it has been removed after amputation are known as phantom limb sensations. These sensations can be painful, sometimes becoming chronic and lasting for several years (or called phantom pain). Medical treatment for these individuals is limited. Recent neurobiological investigations of brain plasticity after amputation have revealed new insights into the changes in the brain that may cause phantom limb sensations and phantom pain. In this article, I review recent progresses of the cortical plasticity in the anterior cingulate cortex (ACC), a critical cortical area for pain sensation, and explore how they are related to abnormal sensory sensations such as phantom pain. An understanding of these alterations may guide future research into medical treatment for these disorders.
Amputation ; Animals ; Brain ; Depression ; Gyrus Cinguli ; Long-Term Potentiation ; Mice ; Phantom Limb ; Sensation