Curcumin Alleviates the Side Effects of Cisplatin on Gastric Emptying of Mice by Inhibiting the Signal Changes of Acetylcholine and Interstitial Cells of Cajal.

Cisplatin is a widely used anticancer drug that has adverse effects on gastrointestinal function. Curcumin is a natural polyphenol extracted from the rhizome of turmeric that has a wide range of biological activities. The present study investigated the effects of cisplatin on gastric emptying in mice and examined whether these can be inhibited by curcumin. We found that pretreatment with curcumin (200 mg/kg/day) for 10-30 days partly inhibited the decreases in gastric emptying rate and body weight induced by cisplatin. Furthermore, cisplatin reduced acetylcholine (ACh) concentration and the messenger RNA (mRNA) level of ACh receptor (AChR) as well as acetylcholinesterase activity in the stomach of mice; caused ultrastructural damage to interstitial cells of Cajal (ICC); and altered the expression of c-kit/stem cell factor and the gap junction protein connexin 43 in ICC. Curcumin pretreatment inhibited the effects of cisplatin on ACh indicators and ICC. These results demonstrate that curcumin can protect against cisplatin-induced gastric emptying disorder and thus has therapeutic potential for alleviating this condition in cancer patients receiving cisplatin chemotherapy.

Online acetylcholinesterase inhibition evaluation by high-performance liquid chromatography-mass spectrometry hyphenated with an immobilized enzyme reactor.

A high-performance liquid chromatography-mass spectrometry technique hyphenated on-line with an immobilized enzyme reactor (IMER) was developed by the use of 3 known acetylcholinesterase (AChE) inhibitors (galanthamine, huperzine A and tacrine). This bioanalytical device allows qualitative comparison of the inhibitory strengths of AChE inhibitors. The AChE inhibitory strengths were evaluated and compared by the corresponding acetylcholine peak areas (mass signal) obtained after a chromatographic separation and the elution through the IMER. Only one injection of the analytes is needed to get this comparative analysis. This bioanalytical device was then applied to the extract of a natural plant, Lycoris radiata, which is known to contain AChE inhibitors such as galanthamine and lycoramine. Aside from the demonstration of the inhibitory activity of the two known AChE inhibitors, the AChE inhibitory activity of another compound (dihydro-latifaliumin C) was revealed. This is the first report describing the AChE inhibitory activity of this compound.

Neuro-protective potential of quercetin during chlorpyrifos induced neurotoxicity in rats.

Chlorpyrifos (CPF) has been considered as one of the most potent organophosphates and is linked to several neurological disorders. On the other hand, Quercetin is a vital plant flavanoid and has been reported to regulate a number of physiological processes in the central nervous system. The present study was conducted to investigate the protective potential of quercetin during chlorpyrifos induced neurotoxicity. Female Wistar rats weighing 150-200 g were divided into four different groups viz: Normal control, CPF treated (13.5 mg/kg.b.wt. every alternate day), Quercetin treated (50 mg/kg.b.wt./day) and combined CPF and quercetin-treated. All the treatments were carried out for a total duration of eight weeks. Chlorpyrifos treatment showed significant alterations in the cognitive behavior and motor activities of rats, which were appreciably improved upon simultaneous supplementation with quercetin. Further, CPF treatment caused a significant inhibition in the enzyme activities of acetylcholinesterase and choline acetyltransferase, but caused an increase in the levels of acetylcholine in the brain. Further, chlorpyrifos exposure significantly elevated the levels of lipid peroxidation and protein carbonyl contents as well as the activities of catalase, superoxide dismutase, which were interestingly found to be decreased following co-treatment with quercetin. In contrast, CPF treatment decreased the activities of glutathione reductase, transferase, as well as levels of reduced and total glutathione in both the cerebrum and cerebellum but co-administration of quercetin, increased these levels. Chlorpyrifos treatment altered the neuro-histoarchitecture, which showed improvement upon quercetin supplementation. Hence, this study suggests that quercetin can be used as a prophylactic intervention to prevent CPF induced neurotoxicity.

Terminalia chebula extract prevents scopolamine-induced amnesia via cholinergic modulation and anti-oxidative effects in mice.

BACKGROUND: Terminalia chebula Retz. (Combretaceae) is a traditional herbal medicine that is widely used in the treatment of diabetes, immunodeficiency diseases, and stomach ulcer in Asia. However, the anti-amnesic effect of T. chebula has not yet been investigated. The present study was designed to determine whether T. chebula extract (TCE) alleviates amnesia induced by scopolamine in mice. We also investigated possible mechanisms associated with cholinergic system and anti-oxidant effects. METHODS: TCE (100 or 200 mg/kg) was orally administered to mice for fourteen days (days 1-14), and scopolamine was intraperitoneally injected to induce memory impairment for seven days (days 8-14). Learning and memory status were evaluated using the Morris water maze. Hippocampal levels of acetylcholine (ACh), acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) were measured ex vivo. Levels of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA) in the hippocampus were also examined. RESULTS: In the Morris water maze task, TCE treatment reversed scopolamine-induced learning and memory deficits in acquisition and retention. TCE reduced hippocampal AChE activities and increased ChAT and ACh levels in the scopolamine-induced model. Moreover, TCE treatment suppressed scopolamine-induced oxidative damage by ameliorating the increased levels of ROS, NO, and MDA. CONCLUSION: These findings suggest that TCE exerts potent anti-amnesic effects via cholinergic modulation and anti-oxidant activity, thus providing evidence for its potential as a cognitive enhancer for amnesia.

Enhanced memory in Wistar rats by virgin coconut oil is associated with increased antioxidative, cholinergic activities and reduced oxidative stress.

CONTEXT: Virgin coconut oil (VCO) has been reported to possess antioxidative, anti-inflammatory and anti-stress properties. OBJECTIVE: Capitalizing on these therapeutic effects, this study investigated for the first time the potential of VCO on memory improvement in vivo. MATERIALS AND METHODS: Thirty male Wistar rats (7-8 weeks old) were randomly assigned to five groups (n = six per group). Treatment groups were administered with 1, 5 and 10 g/kg VCO for 31 days by oral gavages. The cognitive function of treated-rats were assessed using the Morris Water Maze Test. Brains were removed, homogenized and subjected to biochemical analyses of acetylcholine (ACh) and acetylcholinesterase (AChE), antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx) and glutathione reductase (GRx)], lipid peroxidase [malondialdehyde (MDA)] as well as nitric oxide (NO). α-Tocopherol (αT; 150 mg/kg) was also included for comparison purposes. RESULTS: VCO-fed Wistar rats exhibited significant (p < 0.05) improvement of cognitive functions [reduced escape latency (≥ 1.8 s), reduced escape distance (≥ 0.3 m) and increased total time spent on platform (≥ 1 s)]. The findings were accompanied by elevation of ACh (15%), SOD (8%), CAT (≥ 54%), GSH (≥ 20%) and GPx (≥ 12%) and reduction of AChE (≥17%), MDA (> 33%) and NO (≥ 34%). Overall, memory improvement by VCO was comparable to αT. DISCUSSION AND CONCLUSION: VCO has the potential to be used as a memory enhancer, the effect of which was mediated, at least in part, through enhanced cholinergic activity, increased antioxidants level and reduced oxidative stress.

Honeybees Produce Millimolar Concentrations of Non-Neuronal Acetylcholine for Breeding: Possible Adverse Effects of Neonicotinoids.

The worldwide use of neonicotinoid pesticides has caused concern on account of their involvement in the decline of bee populations, which are key pollinators in most ecosystems. Here we describe a role of non-neuronal acetylcholine (ACh) for breeding of Apis mellifera carnica and a so far unknown effect of neonicotinoids on non-target insects. Royal jelly or larval food are produced by the hypopharyngeal gland of nursing bees and contain unusually high ACh concentrations (4-8 mM). ACh is extremely well conserved in royal jelly or brood food because of the acidic pH of 4.0. This condition protects ACh from degradation thus ensuring delivery of intact ACh to larvae. Raising the pH to ≥5.5 and applying cholinesterase reduced the content of ACh substantially (by 75-90%) in larval food. When this manipulated brood was tested in artificial larval breeding experiments, the survival rate was higher with food supplemented by 100% with ACh (6 mM) than with food not supplemented with ACh. ACh release from the hypopharyngeal gland and its content in brood food declined by 80%, when honeybee colonies were exposed for 4 weeks to high concentrations of the neonicotinoids clothianidin (100 parts per billion [ppb]) or thiacloprid (8,800 ppb). Under these conditions the secretory cells of the gland were markedly damaged and brood development was severely compromised. Even field-relevant low concentrations of thiacloprid (200 ppb) or clothianidin (1 and 10 ppb) reduced ACh level in the brood food and showed initial adverse effects on brood development. Our findings indicate a hitherto unknown target of neonicotinoids to induce adverse effects on non-neuronal ACh which should be considered when re-assessing the environmental risks of these compounds. To our knowledge this is a new biological mechanism, and we suggest that, in addition to their well documented neurotoxic effects, neonicotinoids may contribute to honeybee colony losses consecutive to a reduction of the ACh content in the brood food.

Simple New Method of Detecting Lies By Identifying Invisible Unique Physiological Reflex Response Appearing Often Less Than 10-15 Seconds on the Specific Parts of Face of Lying Person; Quick Screening of Potential Murderers & Problematic Persons.

Frequently, we cannot find any significant visible changes when somebody lies, but we found there are significant invisible changes appearing in specific areas of the face when somebody lies and their location often depends on whether the lie is serious with or without physical violence involvement. These abnormalities were detected non-invasively at areas: 1) lobules and c) a small round area of each upper lateral side of forehead; 2) the skin between the base of the 2 orifices of the nose and the upper end of upper lip and 3) Alae of both sides of nose. These invisible significant changes usually last less than 15 seconds after telling a lie. In these areas, Bi-Digital O-Ring Test (BDORT), which received a U.S. Patent in 1993, became significantly weak with an abnormal value of (-)7 and TXB2, measured non-invasively, was increased from 0.125-0.5ng to 12.5-15ng (within the first 5 seconds) and then went back down to less than 1ng (after 15 seconds). These unique changes can be documented semi-permanently by taking photographs of the face of people who tell a lie, within as short as 10 seconds after saying a lying statement. These abnormal responses appear in one or more of the above-mentioned 3 areas 1), 2) & 3). At least one abnormal pupil with BDORT of (-)8-(-)12 & marked reduction in Acetylcholine and abnormal increase in any of 3 Alzheimer's disease associated factors Apolipoprotein (Apo) E4, ß-Amyloid (1-42), Tau protein, viral and bacterial infections were detected in both pupils and forehead of murderers and people who often have problems with others. Analysis of well-known typical examples of recent mass murderers was presented as examples. Using these findings, potential murderers and people who are very likely to develop problems with others can be screened within 5-10 minutes by examining their facial photographs and signatures before school admission or employment.

Early Detection of Autism (ASD) by a Non-invasive Quick Measurement of Markedly Reduced Acetylcholine & DHEA and Increased ß-Amyloid (1-42), Asbestos (Chrysotile), Titanium Dioxide, Al, Hg & often Coexisting Virus Infections (CMV, HPV 16 and 18), Bacterial Infections etc. in the Brain and Corresponding Safe Individualized Effective Treatment.

A brief historical background on Autism & some of the important symptoms associated with Autism are summarized. Using strong Electro Magnetic Field Resonance Phenomenon between 2 identical molecules with identical weight (which received U.S. Patent) non-invasively & rapidly we can detect various molecules including neurotransmitters, bacteria, virus, fungus, metals & abnormal molecules. Simple non- invasive measurement of various molecules through pupils & head of diagnosed or suspected Autism patients indicated that in Autism patients following changes were often found: 1) Acetylcholine is markedly reduced; 2) Alzheimer's disease markers (i.e. ß-Amyloid (1-42), Tau Protein, Apolipoprotein (Apo E4)) are markedly increased; 3) Chrysotile Asbestos is increased; 4) Titanium Dioxide (TiO2) is moderately increased; 5) Al is moderately increased; 6) Hg is moderately increased; 7) Dopamine, Serotonin & GABA are significantly reduced (up to about 1/10 of normal); 8) Often viral infections (such as CMV, HHV-6, HPV-16, HPV-18, etc.), and Bacterial infections (such as Chlamydia trachomatis, Mycobacterium TB, Borrelia Burgdorferi, etc.) coexist. Research by others on Autism spectrum disorder (ASD) shows that it is a group of complex neurodevelopmental disorders, with about 70% of ASD patients also suffering from gastro-intestinal problems. While Alzheimer disease (AD) is characterized by formation of 1) Amyloid plaques, 2) Neurofibrillary tangles inside of neurons, and 3) Loss of connections between neurons. More than 90% of AD develops in people over the age of 65. These 3 characteristics often progressively worsen over time. Although Autism Spectrum Disorder and Alzheimer's disease are completely different diseases they have some similar biochemical changes. Eight examples of such measurement & analysis are shown for comparison. Most of Autism patients improved significantly by removing the source or preventing intake of Asbestos, TiO2, Al & Hg or enhancing urinary output of above abnormal substances & coexisting infections, if treatment is given early. When HPV-16 & HPV-18 coexist, at triangular central area of the top of head, in addition to inability to talk, severe neuromuscular problems of lower extremity were found to also exist. However, if treatment is given 3-4 years after onset of Autism symptoms, even when successful biochemical reduction of above abnormal substances occurs, clinical improvement is less significant, since permanent damage in brain tissue seems to already exist. Therefore, early diagnosis & early treatment is very important for both Autism & Alzheimer's disease. In addition the optimal doses of Vitamin D3 and Taurine may play an important role in the future treatment of Autism, Alzheimer's Disease and memory disturbances by significantly increasing Acetylcholine and DHEA levels, enhancing the excretion of toxic substances in the urine, as well as having an anticancer effect.

[Effect of icariin on learning and memory abilities and activity of cholinergic system of senescence-accelerated mice SAMP10].

OBJECTIVE: To investigate the effect of icariin (ICA) on learning and memory abilities and cholinergic system in senescence-accelerated mice SAMP10. METHOD: The 8-month-old senescence-accelerated mice were randomly divided into the model SAMP10 group and the positive Donepezil group (1 mg x kg(-1)) and ICA groups (50, 100, 200 mg x kg(-1)), with 12 mice in each group. Another 12 8-month-old mice SAMR1 were selected as the normal control group. After 30 days of oral administration, Morris water maze, SMG-2 water maze and experimental platform were used to test the effects of ICA on learning and memory abilities of SAMP10 groups. By colorimetric determination of AChE activity in the cortex, enzyme-linked immunosorbent assay detection of ACh, ChAT, MCBC of the cerebral cortex, the effect of ICA on the cholinergic system of SAMP10 was observed. RESULT: ICA could improve the abilities of space exploration and positioning navigation of SAMP10, shorten the latency in SMG-2 water maze, enhance their jumping ability in response to the passive test, and increase levels of ACh, ChAT, MCBC in the cerebral cortex of SAMP10. But its active effect on AChE in SAMP10 cortex was not obvious. CONCLUSION: Different doses of icariin can improve learning and memory abilities of SAMP10 to varying degrees, which may be related to its effect on the cholinergic system.

Newly discovered quick, non-invasive screening method of bone marrow malignancies including various leukemias, Hodgkin's lymphoma, non-Hodgkin's lymphoma, & multiple myeloma by abnormality of small rectangular area within bone marrow organ representation areas of the face.

Diagnoses of bone marrow associated malignancies such as Acute & Chronic Lymphocytic Leukemia, Acute & Chronic Myelogenous (Myeloid) Leukemia, Hodgkin's Lymphoma & Non-Hodgkin's Lymphoma, and Multiple Myeloma are often missed without a blood test. However, in 2008, Omura Y reported several newly discovered organ representation areas that exist between the lower end of the eyebrows and upper end of the upper eyelid. This space was divided into 5 organ representation areas. The first space (more than 1/4 of entire space) near the side of the face (temple) is the bone marrow representation area (BMRA). Therefore, we examined the bone marrow representation areas non-invasively using the Bi-Digital O-Ring Test (BDORT). When the small rectangular shaped part of the BMRA is strong negative (-) with more than -2, often there is a malignancy associated with bone marrow. In this area, we found 1) Integrin alpha5beta1 & Oncogen C-fos Ab2 increased very significantly between 125-300 ng BDORT units; 2) very high Chrysotile Asbestos (0.11-0.14 mg); 3) markedly reduced Acetylcholine of less than 1 ng; 4) significantly reduced telomere of less than 1 yg (= 10(-24) g); and 5) Increased 8-OH-dG (often more than 5 ng). Once the abnormal small rectangular area is localized by BDORT, by detecting the specific microscope slide which produces EMF (electromagnetic field) resonance, one can diagnose these malignancies non-invasively in about 10 minutes. When a subject has any one of the above 7 types of bone marrow associated malignancies, the 5 aforementioned abnormal parameters can be detected. When Acetylcholine is markedly reduced to 0.25 ng or less, 8-OH-dG is 10 ng or higher, and Sirtuin 1 (one of the 7 mammalian longevity genes products) in both the Hippocampus and the body is 0.025 pg or less, most of the patients have a very poor prognosis. However, we found that increasing normal cell telomere & longevity gene product Sirtuin 1 can often improve both pathology & prognosis. All measurements are in BDORT units (the weight required to produce maximum EMF resonance).

Ginkgo biloba leaf extract (EGb 761®) and its specific acylated flavonol constituents increase dopamine and acetylcholine levels in the rat medial prefrontal cortex: possible implications for the cognitive enhancing properties of EGb 761®.

Experimental and clinical data suggest that the Ginkgo biloba standardized extract EGb 761® exerts beneficial effects in conditions which are associated with impaired cognitive function. However, the neurochemical correlates of these memory enhancing effects are not yet fully clarified. The aim of this study was to examine the effect of repeated oral administration of EGb 761® and some of its characteristic constituents on extracellular levels of dopamine (DA), noradrenaline (NA), serotonin (5-HT), acetylcholine (ACh) and the metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the medial prefrontal cortex (mPFC) of awake rats by use of in vivo microdialysis technique. Subacute (14 days, once daily), but not acute, oral treatment with EGb 761® (100 and 300 mg/kg) or the flavonoid fraction, which represents about 24% of the whole extract caused a significant and dose-dependent increase in extracellular DA levels in the mPFC. Repeated administration of EGb 761® also caused a modest but significant increase in the NA levels, whereas the concentrations of 5-HT and those of the metabolites DOPAC, HVA and 5-HIAA were not affected. The same treatment regimen was used in a subsequent study with the aim of investigating the effects of two Ginkgo-specific acylated flavonols, 3-O-(2''-O-(6'''-O-(p-hydroxy-trans-cinnamoyl)-ß-D-glucosyl)-α-L-rhamnosyl)quercetin (Q-ag) and 3-O-(2''-O-(6'''-O-(p-hydroxy-trans-cinnamoyl)-ß-D-glucosyl)-α-L-rhamnosyl)kaempferol (K-ag). Both compounds together represent about 4.5% of the whole extract. Repeated oral treatment with Q-ag (10 mg/kg) for 14 days caused a significant increase in extracellular DA levels of 159% and extracellular acetylcholine (ACh) levels of 151% compared to controls. Similarly, administration of K-ag (10 mg/kg) induced a significant rise of DA levels to 142% and ACh levels to 165% of controls, whereas treatment with isorhamnetin, an O-methylated aglycon component of EGb 761® flavonol glycosides had no effect. None of the tested flavonoids had a significant effect on extracellular DOPAC and HVA levels. The present findings provide evidence that the subacute treatment with EGb 761® and its flavonol constituents increases DA and ACh release in the rat mPFC, and suggest that the two Ginkgo-specific acylated flavonol glycosides Q-ag and K-ag are active constituents contributing to these effects. As seen for isorhamnetin, the effect on neurotransmitter levels seems not to be a general effect of flavonols but rather to be a specific action of acylated flavonol glycosides which are present in EGb 761®. The direct involvement of these two flavonol derivatives in the increase of dopaminergic and cholinergic neurotransmission in the prefrontal cortex may be one of the underlying mechanisms behind the reported effects of EGb 761® on the improvement of cognitive function.

Acetate-dependent mechanisms of inborn tolerance to ethanol.

AIMS: To clarify the role of acetate in neurochemical mechanisms of the initial (inborn) tolerance to ethanol. METHODS: Rats with low and high inborn tolerance to hypnotic effect of ethanol were used. In the brain region homogenates (frontal and parietal cortex, hypothalamus, striatum, medulla oblongata) and brain cortex synaptosomes, the levels of acetate, acetyl-CoA, acetylcholine (AcH), the activity of pyruvate dehydrogenase (PDG) and acetyl-CoA synthetase were examined. RESULTS: It has been found that brain cortex of rats with high tolerance to hypnotic effect of ethanol have higher level of acetate and activity of acetyl-CoA synthetase, but lower level of acetyl-СCoA and activity of PDG. In brain cortex synaptosomes of tolerant rats, the pyruvate oxidation rate as well as the content of acetyl-CoA and AcH synthesis were lower when compared with intolerant animals. The addition of acetate into the medium significantly increased the AcH synthesis in synaptosomes of tolerant, but not of intolerant animals. Calcium ions stimulated the AcH release from synaptosomes twice as high in tolerant as in intolerant animals. Acetate eliminated the stimulating effect of calcium ions upon the release of AcH in synaptosomes of intolerant rats, but not in tolerant animals. As a result, the quantum release of AcH from synaptosomes in the presence of acetate was 6.5 times higher in tolerant when compared with intolerant rats. CONCLUSION: The brain cortex of rats with high inborn tolerance to hypnotic effect of ethanol can better utilize acetate for the acetyl-CoA and AcH synthesis, as well as being resistant to inhibitory effect of acetate to calcium-stimulated release of AcH. It indicates the metabolic and cholinergic mechanisms of the initial tolerance to ethanol.

Effect of Convolvulus pluricaulis Choisy and Asparagus racemosus Willd on learning and memory in young and old mice: a comparative evaluation.

A dose dependent enhancement of memory was observed with A. racemosus and C. pluricaulis treatment as compared to control group when tested on second day. A. racemosus and C. pluricaulis at the dose of 200 mg/kg, po showed significantly higher percent retentions, than piracetam. Multiple treatment with A. racemosus and C. pluricaulis for three days also demonstrated significant dose dependent increase in percent retentions as compared to control group. The effect was more prominent with C. pluricaulis as compared with piracetam and A. racemosus. A significantly lower percent retention in aged mice was observed as compared to young mice. Aged mice (18-20 months) showed higher transfer latency (TL) values on first and second day (after 24 h) as compared to young mice, indicating impairment in learning and memory. Pretreatment with A. racemosus and C. pluricaulis for 7 days enhanced memory in aged mice, as significant increase in percent retention was observed. Significantly higher retention was observed with C. pluricaulis (200 mg/kg; po) as compared with piracetam (10 mg/kg/; po). Post-trial administration of C. pluricaulis and A. racemosus extract demonstrated significant decrease in latency time during retention trials. Hippocampal regions associated with the learning and memory functions showed dose dependent increase in AChE activity in CA 1 with A. reacemosus and CA3 area with C. pluracaulis treatment. The underlying mechanism of these actions of A. racemosus and C. pluricaulis may be attributed to their antioxidant, neuroprotective and cholinergic properties.

Comparison of ginsenosides Rg1 and Rb1 for their effects on improving scopolamine-induced learning and memory impairment in mice.

Rg1 and Rb1 are two major active compounds of ginseng that facilitate learning and memory. The present study aimed to compare the nootropic effects of Rg1 and Rb1 in a scopolamine induced dementia mice model. After 6 and 12 mg/kg of Rg1 and Rb1 intraperitoneal administration to mice for 7 days, their effects were assessed using the step-down passive avoidance (SD) and the Morris water maze (MWM) tests, the acetylcholinesterase (AChE) activity, acetylcholine (ACh) content and serotonin (5-HT) level in the hippocampus were analysed after SD and MWM tests. The results showed that Rg1 and Rb1 ameliorated cognition-deficiency in mice with dementia. Rg1 showed stronger effects than Rb1 on escape acquisition in MWM. Both Rg1 and Rb1 increased ACh levels in the hippocampus, but Rg1 inhibited AChE activity while Rb1 had no effect on AChE activity. Both Rg1 and Rb1 inhibited the decrease of 5-HT induced by scopolamine, but Rb1 was more active than the same dose of Rg1. These results demonstrate that multiple administrations of Rg1 and Rb1 are effective in improving memory deficiency induced by scopolamine. Rg1 appears to be more potent than Rb1 in improving acquisition impairment, and the two ginsenosides may act through different mechanisms.

Nuevos conceptos sobre la generación y el mantenimiento de la vigilia / New concepts in relation to generating and maintaining arousal

Introducción. Concebido en 1949 por las investigaciones de Moruzzi y Magoun, el concepto de sistema reticular activador ascendente (SRAA) fue de capital importancia para entender la fisiología de la vigilia y del sueño, así como para explicar las bases fisiopatológicas de enfermedades caracterizadas por insomnio, hipersomnia o coma. A sesenta años de este descubrimiento, los avances en el conocimiento de la anatomía, electrofisiología y neuroquímica de los circuitos implicados en la generación y el mantenimiento de la vigilia han determinado que el concepto original del SRAA fuera reevaluado. Sin embargo, a pesar de que patologías que afectan de una forma u otra el estado de vigilia son comunes en el manejo diario de distintas disciplinas médicas, los nuevos conceptos fisiológicos acerca de los sistemas activadores (generadores de vigilia) no son manejados por gran parte del cuerpo médico. Desarrollo. El presente trabajo es una breve actualización sobre los sistemas activadores, destacando los conceptos que pueden ser más rápidamente aplicados para entender la fisiopatología de la vigilia. Conclusiones. Los nuevos conceptos sobre los sistemas activadores son los siguientes: a) los sistemas activadores no sólo se encuentran en la formación reticulada del tronco encefálico, sino que incluyen regiones específicas del hipotálamo posterior y el cerebro basal anterior; b) los sistemas activadores están compuestos por distintos grupos neuronales que actúan mediante neurotransmisores o neuromoduladores específicos; y c) los sistemas activadores generan vigilia, modificando directamente la actividad talámica y cortical (AU)

Introduction. First conceived in 1949 by the research conducted by Moruzzi and Magoun, the concept of the ascending reticular activating system (ARAS) played a vital role in understanding the physiology of sleep and arousal, as well as in explaining the pathophysiological bases of diseases characterised by insomnia, hypersomnia or coma. Sixty years after this discovery, advances in our knowledge of the anatomy, electrophysiology and neurochemistry of the pathways involved in the generation and maintenance of arousal have made it necessary to reassess the original concept of ARAS. Nevertheless, in spite of the fact that the pathologies which, in some way or another, affect the state of arousal are common in the daily practice of different medical disciplines, the new physiological concepts in relation to the activating systems (generators of arousal) are not dealt with by a large number of medical practitioners. Development. This work is a brief update on the activating systems, with special attention given to the concepts that can be applied most readily in order to gain an understanding of the pathophysiology of arousal. Conclusions. The new concepts about the activating systems are as follows: a) the activating systems are not only to be found in the reticular formation of the brain stem, but also include specific regions of the posterior hypothalamus and the anterior basal brain; b) the activating systems are made up of different neuronal groups that act by means of specific neurotransmitters or neuromodulators; and c) the activating systems generate arousal by direct modification of thalamic and cortical activity (AU)

Nuevos conceptos sobre la generación y el mantenimiento de la vigilia / New concepts in relation to generating and maintaining arousal

Introducción. Concebido en 1949 por las investigaciones de Moruzzi y Magoun, el concepto de sistema reticular activador ascendente (SRAA) fue de capital importancia para entender la fisiología de la vigilia y del sueño, así como para explicar las bases fisiopatológicas de enfermedades caracterizadas por insomnio, hipersomnia o coma. A sesenta años de este descubrimiento, los avances en el conocimiento de la anatomía, electrofisiología y neuroquímica de los circuitos implicados en la generación y el mantenimiento de la vigilia han determinado que el concepto original del SRAA fuera reevaluado. Sin embargo, a pesar de que patologías que afectan de una forma u otra el estado de vigilia son comunes en el manejo diario de distintas disciplinas médicas, los nuevos conceptos fisiológicos acerca de los sistemas activadores (generadores de vigilia) no son manejados por gran parte del cuerpo médico. Desarrollo. El presente trabajo es una breve actualización sobre los sistemas activadores, destacando los conceptos que pueden ser más rápidamente aplicados para entender la fisiopatología de la vigilia. Conclusiones. Los nuevos conceptos sobre los sistemas activadores son los siguientes: a) los sistemas activadores no sólo se encuentran en la formación reticulada del tronco encefálico, sino que incluyen regiones específicas del hipotálamo posterior y el cerebro basal anterior; b) los sistemas activadores están compuestos por distintos grupos neuronales que actúan mediante neurotransmisores o neuromoduladores específicos; y c) los sistemas activadores generan vigilia, modificando directamente la actividad talámica y cortical (AU)

Introduction. First conceived in 1949 by the research conducted by Moruzzi and Magoun, the concept of the ascending reticular activating system (ARAS) played a vital role in understanding the physiology of sleep and arousal, as well as in explaining the pathophysiological bases of diseases characterised by insomnia, hypersomnia or coma. Sixty years after this discovery, advances in our knowledge of the anatomy, electrophysiology and neurochemistry of the pathways involved in the generation and maintenance of arousal have made it necessary to reassess the original concept of ARAS. Nevertheless, in spite of the fact that the pathologies which, in some way or another, affect the state of arousal are common in the daily practice of different medical disciplines, the new physiological concepts in relation to the activating systems (generators of arousal) are not dealt with by a large number of medical practitioners. Development. This work is a brief update on the activating systems, with special attention given to the concepts that can be applied most readily in order to gain an understanding of the pathophysiology of arousal. Conclusions. The new concepts about the activating systems are as follows: a) the activating systems are not only to be found in the reticular formation of the brain stem, but also include specific regions of the posterior hypothalamus and the anterior basal brain; b) the activating systems are made up of different neuronal groups that act by means of specific neurotransmitters or neuromodulators; and c) the activating systems generate arousal by direct modification of thalamic and cortical activity (AU)

Arsenic-induced changes in optic tectal histoarchitecture and acetylcholinesterase-acetylcholine profile in Channa punctatus: amelioration by selenium.

Fish (Channa punctatus Bloch) were exposed in vivo for 14 days to non-lethal doses of As2O3 (10% LC50 and 5% LC50). Several endpoints related to histoarchitectural and acetylcholine-acetylcholinesterase (ACh-AChE) profile in the optic tectum were evaluated. Histological examination showed aggregated, disorganized and necrotic cells with irregular outlines in the different layers of optic tectum in the As-treated fish. The histopathological changes were more pronounced on day 7 than on other days and the damage was found to recover on day 14. ACh content and AChE activity demonstrated the usual inverse trend. Arsenic treatment was associated with a dose-dependent increase in AChE activity on day 1, a decrease on day 2 and reactivation on day 7, returning to the basal level on day 14. In vitro inhibition kinetics were set up to determine I50 (35 microM) concentration of As2O3. The ameliorative potential of selenium on arsenic-mediated inhibition of AChE revealed a positive role of Se, especially when Se preceded As2O3 treatment, either in vitro or in vivo.

Amphiphilic p-sulfonatocalix[4]arene-coated CdSe/ZnS quantum dots for the optical detection of the neurotransmitter acetylcholine.

Water-soluble CdSe/ZnS (core-shell) semiconductor quantum dots surface-modified with tetrahexyl ether derivatives of p-sulfonatocalix[4]arene were synthesized for the optical detection of the neurotransmitter acetylcholine.

Inhibition of acetaldehyde metabolism decreases acetylcholine release in medial frontal cortex of freely moving rats.

The effect of high acetaldehyde (ACe) on acetylcholine (ACh) release was studied in vivo in the medial frontal cortex (mfc) of freely moving rats using brain microdialysis coupled with high performance liquid chromatography and an electrochemical detector. Ethanol (EtOH) and ACe concentrations were quantified simultaneously in the mfc of awake rats by in vivo microdialysis followed by head-space gas chromatography. Rats were treated intraperitoneally with saline, EtOH (1 and 2 g/kg) or cyanamide (CY, 50 mg/kg, a potent aldehyde dehydrogenase inhibitor) plus EtOH (1 and 2 g/kg). No significant effect on ACh levels was observed in saline groups, as compared to baseline value. The basal level of ACh in the dialysate was about 0.30 +/- 0.04 pmol/20 microl, and this value was reduced significantly in the EtOH (1 and 2 g/kg) and CY + EtOH (1 and 2 g/kg) groups for 240 min after EtOH administration. The time courses of ACh release continued to decrease significantly after EtOH administration in the CY + EtOH (1 and 2 g/kg) groups compared to the values in the saline and EtOH (1 and 2 g/kg) groups. A significant decrease in ACh release was observed from 140 to 240 min after EtOH dosing in the EtOH (1 and 2 g/kg) groups, as compared to saline groups. EtOH and ACe concentrations in the mfc were first determined at 15 min after a dose of EtOH, reached a peak at 30 min and then gradually decreased in the CY + EtOH (1 and 2 g/kg) groups. The present study suggests that both EtOH and ACe concentration in the brain can decrease in vivo ACh release in the mfc of free-moving rats, and the ACe-induced decrease in ACh levels was significantly higher than EtOH.

Effects of isoflurane on prefrontal acetylcholine release and hypothalamic Fos response in young adult and aged rats.

This experiment investigated the influence of age on prefrontal acetylcholine (ACh) release and Fos response in the hypothalamic paraventricular nucleus and the nucleus tractus solitarius (NTS) of rats following isoflurane anesthesia. It is known that isoflurane decreases acetylcholine release in most brain regions. In the present study, we found that the level of prefrontal acetylcholine was significantly lower in 28-month-old rats (14% of baseline) than in 3-month-old rats (38% of baseline) during 2 h of isoflurane anesthesia (P < 0.05). The old rat group showed significantly greater Fos induction in the paraventricular nucleus compared to the young adult rat group (P < 0.05), indicating that the old rats were subjected to stress. No difference in Fos response was noted in the nucleus tractus solitarius. The old rats displayed a significant increase in feeding behavior during the 3-h recovery period (P < 0.05), but there was no difference in overall acetylcholine levels. Taken together, these findings suggest that isoflurane anesthesia influences old rats more profoundly than young adult rats with regard to reductions in acetylcholine release and stress responses. This may have implications for understanding the development of postoperative delirium in aged patients.