衰老大鼠的某些脑区组织中游离氨基酸水平的改变

使用D 半乳糖建立衰老大鼠模型组与同龄、同饲的正常对照组大鼠的某些脑区游离氨基酸 (FAA)水平的比较发现 :( 1 )衰老模型组的海马、纹状体以及皮层等脑区中谷氨酸 (Glu)、天门冬氨酸 (Asp)水平明显降低 ;( 2 )γ 氨基丁酸 (GABA)水平在衰老模型组大鼠的海马 ,纹状体以及小脑等脑区中明显升高 ;( 3)衰老模型组的皮层、小脑、海马、纹状体等脑区的牛磺酸 (Tau)水平明显下降。以此探讨动物衰老与脑区游离氨基酸水平的关系     

Regular Moderate or Intense Exercise Prevents Depression-Like Behavior without Change of Hippocampal Tryptophan Content in Chronically Tryptophan-Deficient and Stressed Mice

Regular exercise has an antidepressant effect in human subjects. Studies using animals have suggested that the antidepressant effect of exercise is attributable to an increase of brain 5-hydroxytryptamine (5-HT); however, the precise mechanism underlying the antidepressant action via exercise is unclear. In contrast, the effect of 5-HT on antidepressant activity has not been clarified, in part because the therapeutic response to antidepressant drugs has a time lag in spite of the rapid increase of brain 5-HT upon administration of these drugs. This study was designed to investigate the contribution of brain 5-HT to the antidepressant effect of exercise. Mice were fed a tryptophan-deficient diet and stressed using chronic unpredictable stress (CUS) for 4 weeks with or without the performance of either moderate or intense exercise on a treadmill 3 days per week. The findings demonstrated that the onset of depression-like behavior is attributable not to chronic reduction of 5-HT but to chronic stress. Regular exercise, whether moderate or intense, prevents depression-like behavior with an improvement of adult hippocampal cell proliferation and survival and without the recovery of 5-HT. Concomitantly, the mice that exercised showed increased hippocampal noradrenaline. Regular exercise prevents the impairment of not long-term memory but short-term memory in a 5-HT-reduced state. Together, these findings suggest that: (1) chronic reduction of brain 5-HT may not contribute to the onset of depression-like behavior; (2) regular exercise, whether moderate or intense, prevents the onset of chronic stress-induced depression-like behavior independent of brain 5-HT and dependent on brain adrenaline; and (3) regular exercise prevents chronic tryptophan reduction-induced impairment of not long-term but short-term memory.     

Blood Corticosterone Concentration and Differential Blood-Count in Stressed Norway Rats with Different Modes of Behavior

We studied dynamics of leukocyte composition and corticosterone content in the peripheral blood of male Norway rats after long-term selection for tame or aggressive behavior immediately after 20 min restrain as well as 2 and 4 h later. The stressor changed corticosterone concentration and the proportion of various types of leukocytes in the both experimental groups. Quantitatively, the changes were more pronounced in the group of aggressive animals.     

Characterization of the NR1, NR2A, and NR2C receptor proteins.

N-Methyl-D-aspartate (NMDA) receptor subunits were characterized with seven polyclonal antibodies. The antibodies were directed against NR1-A, NR2A-N1, and NR2C-N1, representing N-terminal sequences of the NR1, NR2A, and NR2C subunits, and against NR1-E, NR2A-C1, and NR2C-C1, derived from C-terminal sequences of these subunits. The anti-NR1-D antibody was raised against the putative internal loop of NR1. A size of 118 kDa was found in sodium dodecyl sulfate-polyacrylamide gel electrophoresis for NR1 (from rat brain) detected by anti-NR1-D and -NR1-E, but not anti-NR1-A. With the anti-NR1-A antibody, a 125-kDa protein was discovered that may represent a glutamate receptor not yet characterized. NR2A and NR2C were identified as proteins with sizes of 175 and 140 kDa, respectively. Enzymatic N-deglycosylation generated a 97-kDa protein from NR1, a 105-kDa protein from the 125-kDa protein, a 162-kDa protein from NR2A, and a 127-kDa protein from NR2C. In contrast to the deglycosylation product of the NR2A, the 97- and 127-kDa proteins derived from NR1 and NR2C, respectively, were found significantly smaller than the molecular masses of 103 and 141 kDa, respectively, predicted on the basis of DNA data. These products may represent truncated proteins. The tissue content of the NR1 and NR2A was high in bovine hippocampus and cortex but lower in the cerebellum. In contrast, NR2C was solely found in the cerebellum. The 125-kDa protein was highest in the cerebellum and cortex.     

Levels of Catechols in Epileptogenic and Nonepileptogenic Regions of the Human Brain

Recent reports about tyrosine hydroxylase and alpha 1-adrenoceptors in epileptic foci have suggested increased regional catecholaminergic activity, which may serve a compensatory, inhibitory role. We measured levels of catechols, including the precursor 3,4-dihydroxyphenylalanine (DOPA) and the catecholamines dopamine (DA) and norepinephrine (NE), in surgically removed foci identified by electrocorticography and in nonepileptogenic sites from 23 patients with intractable temporal lobe epilepsy. The following values (mean +/- 1 SD) were obtained: DOPA = 142 +/- 60 ng/g of protein in the focus vs. 115 +/- 39 ng/g in the nonfocus (p less than 0.01); DA = 168 +/- 85 vs. 106 +/- 54 ng/g (p less than 0.001); and NE = 267 +/- 117 vs. 181 +/- 80 ng/g (p less than 0.001). The results are consistent with increased catecholaminergic activity in epileptic foci.     

Maternal Undernutrition During Lactation: Effect on Amino Acids in Brain Regions of Offspring

Sprague-Dawley dams were fed either a protein-calorie deficient or control diet from day 5 to day 21 after parturition. The concentrations of seven amino acids (aspartate, glutamate, gamma-aminobutyric acid, glycine, glutamine, serine, and taurine) were determined in brain regions from 17-day-old undernourished offspring and from 35-day-old rehabilitated rats. The brain regions examined were the cortex, cerebellum, corpus striatum, hippocampus, hypothalamus, brainstem, and midbrain. At 17 days of age, taurine was the amino acid with the highest concentration, whereas at 35 days glutamate had the highest concentration. This change was due to the fact that the concentration of taurine decreased significantly in all brain regions between 17 and 35 days, whereas the concentration of glutamate remained high or increased somewhat in all brain regions except the hypothalamus and brainstem. When the age-matched offspring of control and undernourished rats were compared, several interesting and significant differences were found. The concentrations of glutamate and aspartate were significantly lower (decreased 16-34%) in the cerebellum, brainstem, cortex, and midbrain in 17-day-old undernourished rats. The aspartate level was also significantly decreased in the corpus striatum and hypothalamus in 17-day-old offspring. However, the deficiencies of aspartate and glutamate were transient and reversible. In contrast, the concentration of taurine was increased in the hypothalamus (31%) and hippocampus (12-33%) at both 17 and 35 days of age and in the midbrain (17%) at 17 days. Other transient abnormalities in amino acid levels were found in undernourished offspring. The results of these experiments suggest that undernutrition during lactation causes delayed CNS development, which is manifested in altered concentrations of the neurotransmitters aspartate, glutamate, and taurine.     

Effects of Chronic Light/Dark Cycle on Iron Zinc and Copper Levels in Different Brain Regions of Rats

In this study, we aimed to investigate whether chronic shift in light/dark cycle alters brain trace element concentrations. For this purpose, 20 male Wistar albino adult rats were weighed and randomly divided into three groups. The first group (n?=?6) was the control and had been subjected to 12/12-h light/dark cycle for 30?days. The second group (n?=?7) was subjected to 6/18-h light/dark cycle for 15?days, and the third group (n?=?7) was also subjected to 6/18-h light/dark cycle for 15?days and then returned to normal 12/12-h light/dark cycle for 15?days. When light/dark cycle protocols were completed, tissue specimens of the frontal lobe, temporal lobe, and brain stem were collected. Iron (Fe), zinc (Zn), and copper (Cu) concentrations of the frontal lobe, temporal lobe, and brain stem were determined by an atomic absorption spectrophotometer. When compared with controls, Fe levels of the temporal lobe significantly increased in 6/18-h light/dark cycle group (p?相似文献   

Glutamate Decarboxylase and GABA Aminotransferase Levels in Different Regions of Rat Brain on the Onset of Leptazol Induced Convulsions

The activities of Glutamate decarboxylase (GAD) and Gamma aminobutyric acid (GABA) were studied in three regions of rat brain in heightened neuronal activity resulting in convulsions by Leptazol. These enzymes were studied in preconvulsive, convulsive and post convulsive phases. The activity of GAD decreases significantly in the preconvulsive phase in all the three regions of brain followed by a significant increase during the convulsive and post convulsive phase in cerebral cortex and cerebellum. The activity of GABA-T decreases maximal during the preconvulsive phase followed by convulsive phase. The activity of this enzyme tended to increase to control values when the postconvulsive phase was reached. Therefore, it is suggested that the concomitant decrease of GAD activity and GABA concentration, is probably an important factor in the onset of convulsions.     

Localizing Brain Regions Associated with Female Mate Preference Behavior in a Swordtail

Female mate choice behavior is a critical component of sexual selection, yet identifying the neural basis of this behavior is largely unresolved. Previous studies have implicated sensory processing and hypothalamic brain regions during female mate choice and there is a conserved network of brain regions (Social Behavior Network, SBN) that underlies sexual behaviors. However, we are only beginning to understand the role this network has in pre-copulatory female mate choice. Using in situ hybridization, we identify brain regions associated with mate preference in female Xiphophorus nigrensis, a swordtail species with a female choice mating system. We measure gene expression in 10 brain regions (linked to sexual behavior, reward, sensory integration or other processes) and find significant correlations between female preference behavior and gene expression in two telencephalic areas associated with reward, learning and multi-sensory processing (medial and lateral zones of the dorsal telencephalon) as well as an SBN region traditionally associated with sexual response (preoptic area). Network analysis shows that these brain regions may also be important in mate preference and that correlated patterns of neuroserpin expression between regions co-vary with differential compositions of the mate choice environment. Our results expand the emerging network for female preference from one that focused on sensory processing and midbrain sexual response centers to a more complex coordination involving forebrain areas that integrate primary sensory processing and reward.     

Toxicity of beta-amyloid in HEK293 cells expressing NR1/NR2A or NR1/NR2B N-methyl-D-aspartate receptor subunits

Neurotoxicity induced by beta-amyloid peptide (Abeta) involves glutamate toxicity, resulting from overactivation of N-methyl-D-aspartate (NMDA) receptors and elevation of intracellular calcium. However, the heterogeneity of the NMDA receptors, frequently composed of NR1 and NR2A-D subunits, has been less studied. Thus, we determined the contribution of NMDA receptor subtypes on Abeta(1-40) toxicity in HEK293 cells transiently expressing NR1/NR2A or NR1/NR2B subunits. Analysis of lactate dehydrogenase (LDH) release and trypan blue exclusion revealed an increase in Abeta(1-40) toxicity upon NR1/NR2A expression, compared to NR1/NR2B, indicating loss of plasma membrane integrity. Furthermore, Abeta(1-40) decreased intracellular ATP in cells expressing NR1/NR2A. MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate), a noncompetitive NMDA receptor antagonist, partially prevented the decrease in cell viability and the energy impairment. These differences were not accounted for by the activation of caspases 2, 3, 8 and 9 or calpains or by DNA fragmentation, excluding the hypothesis of apoptosis. Functional NR1/NR2A and NR1/NR2B receptor subtypes were further evidenced by single-cell calcium imaging. Stimulation of NR1/NR2A receptors with NMDA/glycine revealed an increase in intracellular calcium in cells pre-exposed to Abeta(1-40). Opposite effects were observed upon activation of NR1/NR2B receptors. These results suggest that NR1/NR2A-composed NMDA receptors mediate necrotic cell death in HEK293 cells exposed to Abeta(1-40) through changes in calcium homeostasis.     

Changes in iNOS,GFAP and NR1 Expression in Various Brain Regions and Elevation of Sphingosine-1-phosphate in Serum after Immobilized Stress

Several studies have been suggested that long-term exposure to stress has detrimental effects on various brain functions and leads to neurodegenerative changes. However, the precise mechanism by which stress induces brain damage or neurodegenerative change is still a matter of debate. This study investigated the damage of neuronal cells involving in the expression of iNOS, NR1, and GFAP in various brain regions and characterized the change of sphingolipid metabolites as a biomarker of physiological change in serum after 3 weeks of repeated immobilization. In this report, the expression of iNOS, GFAP and NR1 in the brain of rats exposed to chronic immobilization stress was investigated. The expression of iNOS, GFAP and NR1 was elevated in the cortex and hippocampal area after 3 weeks of repeated immobilization. Immunoreactivity for GFAP and vimentin, as a marker of reactive gliosis, was also elevated in the cortex and hippocampus. The level of sphingolipids was measured in order to assess the changes in sphingolipid metabolites in the serum of rats exposed to stress. Interestingly, the level of So-1-P was increased in the plasma of rats subjected to 6-h immobilization stress than repeated immobilization. To further investigate the modulating effect of increased So-1-P in various brain regions, So-1-P was infused into the lateral cerebroventricle at a rate of 100 pmol/10 μl/h for 7 days. The expression of iNOS and NR1 was elevated in the cortex, hippocampus, striatum, and cerebellum after So-1-P infusion into the cerebroventricle, while the level of GFAP was elevated in the hippocampus and striatum. Interestingly, the expression levels of iNOS, GFAP, and NR1 were increased by the direct application of So-1-P to cultured cortical cells. These results suggest that NO production via iNOS expression, the NR1 expression, the activation of astrocytes, and the elevation of So-1-P may cause neurodegenerative changes in rats subjected to chronic immobilization and that the elevation of So-1-P by stress exposure would be one of the stress signal molecules.     

Effects of Chronic Restraint Stress on Feeding Behavior and on Monoamine Levels in Different Brain Structures in Rats

Monoaminergic systems are important modulators of the responses to stress. Stress may influence feeding behavior, and the involvement of monoamines in the control of food intake is well recognized. We investigated the effects induced by chronic-restraint stress, 1 h a day, for 40 days, on eating behavior and on monoamines in distinct brain structures. Increased consumption of sweet pellets, and not of peanuts, was observed. Dopamine (DA), serotonin (5–HT), and their metabolites were measured by HPLC-EC. After chronic restraint, the results observed were decreased 5–HT in hippocampus, with increased 5–HIAA/5–HT; decreased 5–HIAA levels in cortex; reduction in DA in hippocampus, and increased levels in amygdala and hypothalamus; HVA increased in cortex, as well as HVA/DA ratio, while DOPAC/DA decreased. HVA decreased in hypothalamus, as well as HVA/DA, and DOPAC/DA and HVA/DA decreased in the amygdala. These results suggest that restraint stress differentially affects the activity of central dopaminergic and serotonergic neurons, and this may be related to the effects observed in eating behavior.     

NR1, NR2A and NR2C subunits expression after cervical spinal cord transplant and section in dogs

This paper served to evaluate the expression levels of subunits NR1, NR2A and NR2C which are implicated in neuronal plasticity events. A 50% (right half) 4 mm longitudinal resection of the spinal cord was done at the C5-C6 level with preservation of the anterior spinal artery. This was effected in a dog model after either a homologous transplant or a pure spinal cord section. In this study we used two groups of dogs with four individuals each, as well as a control group. The transplant group (n=4) was analyzed at days 3 and 28 post surgery. The section group (n=4) was also analyzed at days 3 and 28 post op. All three groups (transplant, section and control) were evaluated as to the subunit expression in each of the segments corresponding to the transplanted or sectioned sites, the site contralateral to the transplanted or sectioned sites at levels half a centimeter both proximal and distal to the site of transplant and section. The results showed a variety of changes in each of the subunits depending on the group, the segment and the time of evaluation (acute versus chronic). This could be closely related to mechanisms which participate in regeneration and functional recuperation.     

Effect of Chronic Manganese Treatment on Adenosine Tissue Levels and Adenosine A2a Receptor Binding in Diverse Regions of Mouse Brain

In the present study the effects of chronic manganese (Mn) treatment on adenosine A_2a receptor binding in mouse brain have been assessed. Male albino mice were divided in two groups: In the Mn-treated group, the animals were injected intraperitoneally (i.p.) with MnCl₂ (5 mg/kg/day) five days per week during 9 weeks; in the control group, they were injected likewise with a saline solution. A significant decrease of the Kd without alteration of Bmax in the cerebellum and, an increase of the Kd and Bmax in hippocampus of mice treated with Mn were found. Also, an increase of Kd in frontal cortex was observed. The binding parameters in caudate nucleus, olfactory bulb and hypothalamus were not altered by Mn. A significant decrease in the adenosine concentration in caudate nucleus, olfactory bulb and hypothalamus, without significant changes in hippocampus, frontal cortex and cerebellum was also detected. These findings suggest that chronic administration of Mn could affect adenosine receptor function and turnover, depending on the brain region analyzed.     

Neurosteroids allosterically modulate the ion pore of the NMDA receptor consisting of NR1/NR2B but not NR1/NR2A

Neurosteroids are endogenously derived compounds, mediating rapid effects in the central nervous system. They participate in vital processes, including memory and learning, neuroplasticity, and neuroprotection in Alzheimer’s disease. However, the mechanisms behind those effects remain to be elucidated. The neurosteroids pregnenolone sulphate (PS) and pregnanolone sulphate (3α5βS) have recently been shown to allosterically alter the NMDA receptor in nanomolar concentrations. Those studies featured ifenprodil, which is a dirty drug, with affinity to many targets. In this study we compare the NMDA receptors in the hippocampus to recombinant NMDA receptors, using [³H]-MK-801 as radioligand. The results show that neurosteroids modulate the ifenprodil binding kinetics in a narrow concentration interval, addressing it to the NR2B subunit, since no effects were recorded at recombinant NR1/NR2A receptors. The effects were also seen as changes in the manner ifenprodil displaced or induced the dissociation of [³H]-MK-801. It indicates that the neurosteroidal effects indeed alter the ion pore of the NMDA receptor, why it is reasonable to believe that these findings have physiological relevance.     

Prenatal Diazepam Exposure Affects β-Adrenergic Receptors in Brain Regions of Adult Rat Offspring

The postnatal development of [3H]dihydroalprenolol binding to beta-adrenergic receptors has been studied in frontal cortex, cerebellum, striatum, and hypothalamus of the rat after prenatal and perinatal exposure to diazepam. Dams were injected subcutaneously with single daily doses of 1 mg of diazepam/kg from day 7 to 20 of gestation or from day 15 of gestation to day 6 after birth. Prenatal exposure had no effect on litter size or length of gestation or on the postnatal development of body and brain weights of the progeny. However, a reduced mortality of the pups was observed in relation to vehicle-treated controls until postnatal day 10. Prenatal diazepam administration decreased [3H]dihydroalprenolol binding in frontal cortex, striatum, and hypothalamus but not in cerebellum. This decrease in beta-adrenergic receptor binding was due to a decrease in receptor density rather than in receptor affinity. In contrast, perinatal diazepam exposure led to a transient decrease in [3H]dihydroalprenolol binding limited to the frontal cortex. The permanent reduction in number of beta-adrenergic receptors, which depends on the scaling and duration of the drug application period, points to the necessity of a prolonged evaluation of effects of exposure to psychotropic drugs in early stages of brain development.