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1.
A growing body of evidence suggests that nucleus accumbens (NAc) plays a significant role not only in the physiological processes associated with reward and satisfaction but also in many diseases of the central nervous system. Summary of the current state of knowledge on the morphological and functional basis of such a diverse function of this structure may be a good starting point for further basic and clinical research. The NAc is a part of the brain reward system (BRS) characterized by multilevel organization, extensive connections, and several neurotransmitter systems. The unique role of NAc in the BRS is a result of: (1) hierarchical connections with the other brain areas, (2) a well-developed morphological and functional plasticity regulating short- and long-term synaptic potentiation and signalling pathways, (3) cooperation among several neurotransmitter systems, and (4) a supportive role of neuroglia involved in both physiological and pathological processes. Understanding the complex function of NAc is possible by combining the results of morphological studies with molecular, genetic, and behavioral data. In this review, we present the current views on the NAc function in physiological conditions, emphasizing the role of its connections, neuroplasticity processes, and neurotransmitter systems.  相似文献   

2.
Cannabis use among pregnant women is increasing worldwide along with permissive sociocultural attitudes toward it. Prenatal cannabis exposure (PCE), however, is associated with adverse outcome among offspring, ranging from reduced birth weight to child psychopathology. We have previously shown that male rat offspring prenatally exposed to Δ9-tetrahydrocannabinol (THC), a rat model of PCE, exhibit extensive molecular, cellular, and synaptic changes in dopamine neurons of the ventral tegmental area (VTA), resulting in a susceptible mesolimbic dopamine system associated with a psychotic-like endophenotype. This phenotype only reveals itself upon a single exposure to THC in males but not females. Here, we characterized the impact of PCE on female behaviors and mesolimbic dopamine system function by combining in vivo single-unit extracellular recordings in anesthetized animals and ex vivo patch clamp recordings, along with neurochemical and behavioral analyses. We find that PCE female offspring do not show any spontaneous or THC-induced behavioral disease-relevant phenotypes. The THC-induced increase in dopamine levels in nucleus accumbens was reduced in PCE female offspring, even when VTA dopamine activity in vivo and ex vivo did not differ compared to control. These findings indicate that PCE impacts mesolimbic dopamine function and its related behavioral domains in a sex-dependent manner and warrant further investigations to decipher the mechanisms determining this sex-related protective effect from intrauterine THC exposure.  相似文献   

3.
Serotonin modulates several physiological and cognitive pathways throughout the human body that affect emotions, memory, sleep, and thermal regulation. The complex nature of the serotonergic system and interactions with other neurochemical systems indicate that the development of depression may be mediated by various pathomechanisms, the common denominator of which is undoubtedly the disturbed transmission in central 5-HT synapses. Therefore, the deliberate pharmacological modulation of serotonergic transmission in the brain seems to be one of the most appropriate strategies for the search for new antidepressants. As discussed in this review, the serotonergic system offers great potential for the development of new antidepressant therapies based on the combination of SERT inhibition with different pharmacological activity towards the 5-HT system. The aim of this article is to summarize the search for new antidepressants in recent years, focusing primarily on the possibility of benefiting from interactions with various 5-HT receptors in the pharmacotherapy of depression.  相似文献   

4.
Acrylamide is a commonly used industrial chemical that is known to be neurotoxic to mammals. However, its developmental toxicity is rarely assessed in mammalian models because of the cost and complexity involved. We used zebrafish to assess the neurotoxicity, developmental and behavioral toxicity of acrylamide. At 6 h post fertilization, zebrafish embryos were exposed to four concentrations of acrylamide (10, 30, 100, or 300 mg/L) in a medium for 114 h. Acrylamide caused developmental toxicity characterized by yolk retention, scoliosis, swim bladder deficiency, and curvature of the body. Acrylamide also impaired locomotor activity, which was measured as swimming speed and distance traveled. In addition, treatment with 100 mg/L acrylamide shortened the width of the brain and spinal cord, indicating neuronal toxicity. In summary, acrylamide induces developmental toxicity and neurotoxicity in zebrafish. This can be used to study acrylamide neurotoxicity in a rapid and cost-efficient manner.  相似文献   

5.
采用ELS清洗剂溶液与铜反应,研究ELS清洗剂除铜效果。实验证明:ELS清洗剂比煤油的除铜效果大大的增加;当溶液的温度在零度以下时,仍然具有一定的效果;ELS清洗剂配成的溶液10h内清洗效果最好,120h以后几乎没有效果;同时,ELS清洗剂对炮管材料没有腐蚀作用。  相似文献   

6.
The developing prenatal brain is particularly susceptible to environmental disturbances. During prenatal brain development, synapses form between neurons, resulting in neural circuits that support complex cognitive functions. In utero exposure to environmental factors such as pharmaceuticals that alter the process of synapse formation increases the risk of neurodevelopmental abnormalities. However, there is a lack of research into how specific environmental factors directly impact the developing neural circuitry of the human brain. For example, selective serotonin reuptake inhibitors are commonly used throughout pregnancy to treat depression, yet their impact on the developing fetal brain remains unclear. Recently, human brain models have provided unprecedented access to the critical window of prenatal brain development. In the present study, we used human neurons and cortical spheroids to determine whether the selective serotonin reuptake inhibitor fluoxetine alters neurite and synapse formation and the development of spontaneous activity within neural circuits. We demonstrate that cortical spheroids express serotonin transporter, thus recapitulating the early developmental expression of serotonin transporter associated with cortical pyramidal neurons. Cortical spheroids also appropriately express serotonin receptors, such as synaptic 5-HT2A and glial 5-HT5A. To determine whether fluoxetine can affect developing neural circuits independent of serotonergic innervation from the dorsal and medial raphe nuclei, we treated cortical neurons and spheroids with fluoxetine. Fluoxetine alters neurite formation in a dose-dependent fashion. Intriguingly, in cortical spheroids, neither acute nor chronic fluoxetine significantly altered excitatory synapse formation. However, only acute, but not chronic fluoxetine exposure altered inhibitory synaptogenesis. Finally, fluoxetine reversibly suppresses neuronal activity in a dose-dependent manner. These results demonstrate that fluoxetine can acutely alter synaptic function in developing neural circuits, but the effects were not long-lasting. This work provides a foundation for future studies to combine serotonergic innervation with cortical spheroids and assess the contributions of fluoxetine-induced alterations in serotonin levels to brain development.  相似文献   

7.
A cross-fostering design was used to examine the effects on brain and behavioral development in mice of pre-and/or postnatal dietary supplementation with n−3 fatty acids. Pregnant mice were fed either of two liquid diets, control (con) or experimental (exp). Each diet provided 3% of the calories in the form of n−6 fatty acids; the experimental diet was supplemented with an additional 1.5% from long chain n−3 fatty acids derived from fish oil. There were four treatment groups, with all pups fostered at birth. These groups were (prenatal diet/ postnatal diet): Group 1, exp/exp; Group 2, exp/con; Group 3, con/exp; Group 4, con/con; a fifth control group (unfostered) was fed lab chow (LC) throughout the study. Animals from the exp/exp and con/con groups were weaned onto lab chow for later behavioral assessment. Prenatal n−3 supplementation resulted in a small acceleration of behavioral development. The adult animals did not differ in visual discrimination learning nor did they differ in visual acuity. During development the fatty acid composition of the brain membrane phospholipids reflected closely that of the pre- and postnatal dietary conditions. Levels of 22∶5n−3 and 22∶6n−3 increased in the n−3 supplemented groups, accompanied by a decrease in levels of 22∶4n−6 and 22∶5n−6; the net effect of these changes was to increase the total levels of C22 fatty acids. While these results support considerable plasticity of the fatty acid composition of the developing brain with respect to the immediate dietary availability of n−3 compounds, they do not support long term effects on learning capacity of n−3 supplementation during the developmental period.  相似文献   

8.
The effect of the polyphenols of coffee pulp on iron absorption was studied using the method of ligated segments in rats. Optimal conditions to measure iron absorption, were determined using as criteria the concentration of Fe59 and the time that produced the highest value of blood radioactivity. A concentration of 0.4 uCi/dose of Fe59 and a 3-hr period were chosen to measure iron absorption. Experimental groups were formed assigning six rats randomly to each group. Each group was injected with a solution of 59Fe and either with the standard polyphenol solution or with the coffee pulp extract, except the control group which was injected with the Fe59 solution only. The effect of two polyphenol concentrations was also studied. Iron uptake from the duodenum was found to be the best indicator of iron absorption when compared to the sum of iron uptake by the tissues (blood, liver, spleen, kidneys, heart and carcass). Therefore, this indicator was used to interpret the results obtained. Catechin, tannic acid and the coffee pulp extract decreased significantly iron absorption when compared with the control group. The level of polyphenols used in these experiments is similar to the amounts consumed by animals fed coffee pulp at a 10% level. Therefore, we can conclude that the antinutritional effect of coffee pulp polyphenols may be partially due to their capacity to bind iron.  相似文献   

9.
In laboratory and field-trapping studies, we exposed fathead minnows (Pimephales promelas) and finescale dace (Chrosomus neogaeus) to hypoxanthine-3-N-oxide and a suite of structurally and functionally similar compounds in order to determine if: (1) hypoxanthine-3-N-oxide functions as a chemical alarm signal in ostariophysan fishes and (2) the purine skeleton, a structural component, or the nitrogen oxide, a functional component, or both act as the molecular trigger in this chemical alarm signaling system. Minnows and dace exhibited significant antipredator responses when exposed to conspecific skin extract or hypoxanthine-3-N-oxide (increased shoaling and decreased area use) and the functionally similar pyridine-N-oxide (increased shoaling) but not to structurally similar molecules lacking a nitrogen oxide functional group or to a swordtail skin extract control. Field-trapping studies revealed similar results. Traps labeled with fathead minnows skin extract, hypoxanthine-3-N-oxide, or pyridine-N-oxide caught significantly fewer fish than did those labeled with distilled water. These data strongly suggest that the nitrogen oxide functional group acts as the chief molecular trigger in the Ostariophysan alarm pheromone system and that, contrary to previous research, hypoxanthine-3-N-oxide may be one of several possible molecules that function as a chemical alarm signal. Here we report the first example of a single functional group capable of eliciting a suite of behavioral responses.  相似文献   

10.
Levant B  Ozias MK  Jones KA  Carlson SE 《Lipids》2006,41(5):407-414
Variation in brain FA composition, particularly decreased DHA (22ŋ6n−3), affects neurodevelopment, altering visual, attentional, and cognitive functions, and is implicated in several neuropsychiatric disorders. To further understand how specific brain processes and systems are affected by variation in brain DHA content, we sought to determine whether specific brain regions were differentially affected by treatments that after brain DHA content. Adult male Long-Evans rats were raised from conception using diet/breeding treatments to produce four groups with distinct brain phospholipid compositions. Total phospholipid FA composition was determined in whole brain and 15 brain regions by TLC/GC. Brain regions exhibited significantly different DHA contents, with the highest levels observed in the frontal cortex and the lowest in the substantia nigra/ventral tegmental area. Increased availability of DHA resulted in increased DHA content only in the olfactory bulb, parietal cortex, and substantia nigra/ventral tegmental area. In contrast, treatment that decreased whole-brain DHA levels decreased DHA content in all brain regions except the thalamus, dorsal midbrain, and the substantia nigra/ventral tegmental area. Alterations in DHA level were accompanied by changes in docosapentaenoic acid (n−6 DPA, 22∶5n−6) content; however, the change in DHA and n−6 DPA was nonreciprocal in some brain regions. These findings demonstrate that the FA compositions of specific brain regions are differentially affected by variation in DHA availability during development. These differential effects may contribute to the specific neurochemical and behavioral effects observed in animals with variation in brain DHA content.  相似文献   

11.
Previously, we found that basal corticosterone pulsatility significantly impacts the vulnerability for developing post-traumatic stress disorder (PTSD). Rats that exhibited PTSD-phenotype were characterized by blunted basal corticosterone pulsatility amplitude and a blunted corticosterone response to a stressor. This study sought to identify the mechanisms underlining both the loss of pulsatility and differences in downstream responses. Serial blood samples were collected manually via jugular vein cannula at 10-min intervals to evaluate suppression of corticosterone following methylprednisolone administration. The rats were exposed to predator scent stress (PSS) after 24 h, and behavioral responses were assessed 7 days post-exposure for retrospective classification into behavioral response groups. Brains were harvested for measurements of the glucocorticoid receptor, mineralocorticoid receptor, FK506-binding protein-51 and arginine vasopressin in specific brain regions to assess changes in hypothalamus–pituitary–adrenal axis (HPA) regulating factors. Methylprednisolone produced greater suppression of corticosterone in the PTSD-phenotype group. During the suppression, the PTSD-phenotype rats showed a significantly more pronounced pulsatile activity. In addition, the PTSD-phenotype group showed distinct changes in the ventral and dorsal CA1, dentate gyrus as well as in the paraventricular nucleus and supra-optic nucleus. These results demonstrate a pre-trauma vulnerability state that is characterized by an over-reactivity of the HPA and changes in its regulating factors.  相似文献   

12.
Brain tissue may be especially sensitive to electromagnetic phenomena provoking signs of neural stress in cerebral activity. Fifty-four adult female Sprague-Dawley rats underwent ELISA and immunohistochemistry testing of four relevant anatomical areas of the cerebrum to measure biomarkers indicating induction of heat shock protein 70 (HSP-70), glucocorticoid receptors (GCR) or glial fibrillary acidic protein (GFAP) after single or repeated exposure to 2.45 GHz radiation in the experimental set-up. Neither radiation regime caused tissue heating, so thermal effects can be ruled out. A progressive decrease in GCR and HSP-70 was observed after acute or repeated irradiation in the somatosensory cortex, hypothalamus and hippocampus. In the limbic cortex; however, values for both biomarkers were significantly higher after repeated exposure to irradiation when compared to control animals. GFAP values in brain tissue after irradiation were not significantly different or were even lower than those of nonirradiated animals in all brain regions studied. Our results suggest that repeated exposure to 2.45 GHz elicited GCR/HSP-70 dysregulation in the brain, triggering a state of stress that could decrease tissue anti-inflammatory action without favoring glial proliferation and make the nervous system more vulnerable.  相似文献   

13.
Little is known about the impairments and pathological changes in the visual system in mild brain trauma, especially repetitive mild traumatic brain injury (mTBI). The goal of this study was to examine and compare the effects of repeated head impacts on the neurodegeneration, axonal integrity, and glial activity in the optic tract (OT), as well as on neuronal preservation, glial responses, and synaptic organization in the lateral geniculate nucleus (LGN) and superior colliculus (SC), in wild-type mice and transgenic animals with overexpression of human TDP-43 mutant protein (TDP-43G348C) at 6 months after repeated closed head traumas. Animals were also assessed in the Barnes maze (BM) task. Neurodegeneration, axonal injury, and gliosis were detected in the OT of the injured animals of both genotypes. In the traumatized mice, myelination of surviving axons was mostly preserved, and the expression of neurofilament light chain was unaffected. Repetitive mTBI did not induce changes in the LGN and the SC, nor did it affect the performance of the BM task in the traumatized wild-type and TDP-43 transgenic mice. Differences in neuropathological and behavioral assessments between the injured wild-type and TDP-43G348C mice were not revealed. Results of the current study suggest that repetitive mTBI was associated with chronic damage and inflammation in the OT in wild-type and TDP-43G348C mice, which were not accompanied with behavioral problems and were not affected by the TDP-43 genotype, while the LGN and the SC remained preserved in the used experimental conditions.  相似文献   

14.
The behaviour of styrene butadiene rubber/acrylonitrile butadiene rubber (SBR/NBR) blends in the environment of chlorinated hydrocarbons, such as carbon tetrachloride, chloroform and dichloromethane, in the temperature range 32–52°C has been investigated. Sulphur, dicumyl peroxide and a mixed system consisting of sulphur and peroxide were used as the vulcanising systems for the matrix. The effects of vulcanising agents, blend composition, solvents and temperature on the sorption characteristics were studied. The sulphur-vulcanised systems exhibited the highest solvent uptake and those with dicumyl peroxide as the vulcanising agent the lowest. This difference has been explained on the basis of the nature of cross links established between the polymer chains during vulcanisation. The solvent uptake increased with an increase in SBR content in the blends when carbon tetrachloride was used as the penetrant, whilst it decreased with SBR content when chloroform and dichloromethane were used as the probes. This behaviour has been explained on the basis of the polarity difference of the solvents. For a given blend system, the solvent uptake was maximum when dichloromethane was used as the solvent and minimum when carbon tetrachloride was used. This has been accounted for in terms of the difference in the size of the penetrants. The intrinsic diffusion coefficient, permeation coefficient, cross link density and interaction parameter were estimated from the sorption data. Thermodynamic parameters such as enthalpy and free energy changes were also calculated. These values indicate that the sorption process in the present systems is exothermic and is more spontaneous in sulphur-vulcanised systems. The experimental results, when compared with different theoretical diffusion models, have been found to be closer to Robeson’s and Maxwell’s models.  相似文献   

15.
[U-14C] Glucose or [1-14C] L-leucine was injected intraperitoneally into 28-day-old undernourished rats and control sibs who were killed 6 hr later. Brain proteins and lipids were extracted and the lipids fractionated by silicic acid column chromatography into cholesterol, glycolipids and phospholipids. The specific activity of labeled carbon derived from [U-14C] glucose in brain proteins was reduced by 25% in undernourished animals when compared to controls. A similar reduction was seen in the specific activity of brain lipids of undernourished animals: 14% for cholesterol, 21% for phospholipids and 35% for glycolipids. When [1-14C] l-leucine was used as a direct precursor of brain protein synthesis, the specific activity in the undernourished group was only 5% less than that found for the controls. This was not statistically significant. The results suggest that there may be a block in the intermediary metabolism of glucose in the brains of undernourished rats that reduces the availability of glucose carbon to the precursor pool used for protein and lipid synthesis.  相似文献   

16.
The risk of accidental bromine (Br2) exposure to the public has increased due to its enhanced industrial use. Inhaled Br2 damages the lungs and the heart; however, adverse effects on the brain are unknown. In this study, we examined the neurological effects of inhaled Br2 in Sprague Dawley rats. Rats were exposed to Br2 (600 ppm for 45 min) and transferred to room air and cage behavior, and levels of glial fibrillary acidic protein (GFAP) in plasma were examined at various time intervals. Bromine exposure resulted in abnormal cage behavior such as head hitting, biting and aggression, hypervigilance, and hyperactivity. An increase in plasma GFAP and brain 4-hydroxynonenal (4-HNE) content also was observed in the exposed animals. Acute and delayed sympathetic nervous system activation was also evaluated by assessing the expression of catecholamine biosynthesizing enzymes, tryptophan hydroxylase (TrpH1 and TrpH2), and tyrosine hydroxylase (TyrH), along with an assessment of catecholamines and their metabolites. TyrH was found to be increased in a time-dependent manner. TrpH1 and TrpH2 were significantly decreased upon Br2 exposure in the brainstem. The neurotransmitter content evaluation indicated an increase in 5-HT and dopamine at early timepoints after exposure; however, other metabolites were not significantly altered. Taken together, our results predict brain damage and autonomic dysfunction upon Br2 exposure.  相似文献   

17.
We studied the foraging behavior ofRhagoletis cerasi females in trees treated with synthetic cherry fruit fly host marking pheromone (HMP) under seminatural conditions (potted trees enclosed in a screen cage). Results show that synthetic HMP (particularly the 8RS-@#@ 15R isomer configuration (racemic mixture)) was highly effective in eliciting behavioral responses similar to those reported in studies using natural HMP. Flies exposed to synthetic pheromone exhibited short tree residence times (i.e., emigrated faster), increased flight frequency rates (measured as number of alightings per/minute), higher irritation indices while on a tree or a fruit, and oviposited fewer eggs per fruit visit than flies exposed to clean trees and fruit (not treated with synthetic HMP). Furthermore, we provide evidence showing that when flies were continuously exposed to an HMP-saturated environment, they exhibited an increased tendency to lay eggs in marked fruit.  相似文献   

18.
Many mammals and birds roll on or rub themselves with millipedes that discharge benzoquinones. Chemicals transferred from millipedes onto the integument of anointing animals are thought to deter ectoparasites. We tested the lone star tick, Amblyomma americanum(L.), for responses to three widespread components of millipede defensive secretions, 1,4-benzoquinone; 2-methyl-1,4-benzoquinone (toluquinone); and 2-methoxy-3-methyl-1,4-benzoquinone (MMB). In toxicity tests, ticks were confined for 1 hr in filter-paper packets treated with serial dilutions of each of the benzoquinones or the commercial acaricide permethrin. Ticks were least affected by toluquinone, and most affected by permethrin. Of the benzoquinones, only MMB showed repellent activity. Behavioral assays were more sensitive than mortality for measuring the effects of the benzoquinones. Latencies for ticks to right themselves and to climb were greater with all compounds, even at the lowest concentrations, than with controls. Ticks exposed to low concentrations of benzoquinones appeared to recover over time, whereas those exposed to high concentrations exhibited behavioral abnormalities 1–3 mo later. Our results indicate that benzoquinones appropriated via anointing may reduce the tick loads of free-ranging animals, although key questions remain on the amounts of these compounds available to and effectively appropriated by anointing animals.  相似文献   

19.
Background: exposure to environmental contaminants has been linked to an increased risk of neurological diseases and poor outcomes. Chemical name of Atrazine (ATR) is 6-chloro-N-ethyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, and it is the most commonly used broad-spectrum herbicide in agricultural crops. Several studies have demonstrated that ATR has the potential to be harmful to the brain’s neuronal circuits. Until today nobody has explored the effect of ATR inhalation on young and aged mice. Methods: young and aged mice were subject to 25 mg of ATR in a vehicle made with saline and 10% of Dimethyl sulfoxide (DMSO) every day for 28 days. At the end of experiment different behavioral test were made and brain was collected. Results: exposure to ATR induced the same response in terms of behavioral alterations and motor and memory impairment in mice but in aged group was more marked. Additionally, in both young and aged mice ATR inhalations induced oxidative stress with impairment in physiological antioxidant response, lipid peroxidation, nuclear factor kappa-light-chain-enhancer of activated B cells (nf-κb) pathways activation with consequences of pro-inflammatory cytokines release and apoptosis. However, the older group was shown to be more sensitive to ATR inhalation. Conclusions: our results showed that aged mice were more susceptible compared to young mice to air pollutants exposure, put in place a minor physiologically response was seen when exposed to it.  相似文献   

20.
Uptake of fatty acids by the developing rat brain   总被引:1,自引:0,他引:1  
Polyunsaturated fatty acids are avidly taken up by the developing rat brain. To explore the specificity of this process, [1-14C]labeled 16∶0, 18∶2n−6, 18∶3n−3, and 22∶6n−3 each were co-injected with [3H]18∶1n−9 into the jugular vein of two-wk-old functionally hepatectomized and shamoperated control rats. The radioactivities present in the brain, liver and serum were assessed 30 min after injection. Uptake of labeled fatty acids into brain lipids steadily increased with increasing degree of unsaturation, with more than twice as much uptake of 22∶6n−3 compared to 16∶0. Phosphatidylcholine was the principal radioactive species in the brain except for animals injected with [1-14C]22∶6n−3, in which more of the label was incorporated into phosphatidylethanolamine. Determination of watersoluble oxidation products in the brain and serum revealed that the greater uptake of the more unsatrated fatty acids did not result from differences in rates of degradation.  相似文献   

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