Posted 20 November 2004 - 12:42 AM
Posted 20 November 2004 - 12:44 AM
From Cosmos
thefirstimmortal, I don't know what the extent and rate of your physical deterioration is but please feel free to discuss your physical situation with fellow nootropic users myself included (as well as scottl who is a physician himself).
Posted 20 November 2004 - 01:13 AM
Posted 20 November 2004 - 02:43 AM
Effect of long term hydergine treatment on the age-dependent loss of mossy fibers and of granule cells in the rat hippocampus.
Amenta F, Jaton AL, Ricci A.
Dipartimento di Sanita Pubblica e Biologia Cellulare, Universita 'Tor Vergata', Rome, Italy; Dipartimento di Scienze Neurologiche, Universita 'La Sapienza', Rome, Italy.
The effects of senescence and of long-term Hydergine treatment on the density and pattern of mossy fibers and on the number of granule cells of the dentate gyrus were studied in the rat hippocampus. Timm's technique for the histochemical demonstration of tissue stores of zinc, associated with quantitative image analysis and microdensitometry, was used for the study of mossy fibers. Consistent with our previous studies, we observed an age-related reduction both in the area occupied by mossy fibers and in the intensity of Timm staining in the mossy fiber area. Moreover, the density of granule cells in the dentate gyrus of hippocampus was reduced with age. Hydergine administration (1 and 3 mg/kg/day, p.o.), started when the rats were 17 months old and continued for 4 months, significantly increased the area occupied by mossy fibers and the intensity of Timm staining in the hippocampus of senescent animals. Moreover, Hydergine treatment was found to counteract the age-dependent decrease in granule cell number in the dentate gyrus of the hippocampus. These findings suggest that treatment with Hydergine is effective in counteracting or in slowing down the morphological disorganization observable in the hippocampal formation with advancing age. Moreover, it is possible that the effects of Hydergine administration in elderly patients might be related to an effect at the level of the hippocampus.
Posted 20 November 2004 - 02:49 AM
Possible supportive effects of co-dergocrine mesylate on antioxidant enzyme systems in aged rat brain.
Sozmen EY, Kanit L, Kutay FZ, Hariri NI.
Ege University, School of Medicine, Department of Biochemistry, Bornova Izmir, Turkey.
Free radical damage is implicated in the course of many diseases, including age-related dementias. Oxidative deamination of primary monoamino oxidase (MAO) produces NH3 and H2O2 with established or potential toxicity. MAO activity is increased in aged rat brain and significantly lowered by chronic hydergine (codergocrine mesylate, Sandoz) treatment. The aim of this study was to investigate the effects of hydergine on enzymatic antioxidant defense systems. Hydergine or vehicle was administered systemically to young (3 months) and aged (18 months) Sprague-Dawley rats for 20 days and 24 h after the termination of the treatment, superoxide dismutase (SOD) and catalase (CAT) activities were determined in some brain regions. SOD and CAT activities were higher in the aged animals and were further increased with hydergine treatment. The increase in SOD levels caused by hydergine treatment in the aged animals were the most prominent in the hippocampus and in the corpus striatum. There was no region-specific effect of hydergine treatment on CAT levels in aged animals. The possible causal relationship between increased MAO activity, a generator of free radicals, and increased antioxidant defense in aging brain require further investigation. Decreasing MAO levels and supporting the antioxidant enzymes may underlie the efficacy of hydergine in the treatment of age related cognitive decline.
Posted 20 November 2004 - 02:51 AM
Co-dergocrine (Hydergine) regulates striatal and hippocampal acetylcholine release through D2 receptors.
Imperato A, Obinu MC, Dazzi L, Carta G, Mascia MS, Casu MA, Gessa GL.
Bernard B. Brodie Department of Neuroscience, University of Cagliari, Italy.
The effect of Co-dergocrine (Hydergine) on acetylcholine (ACh) release in the striatum and hippocampus has been studied by means of brain microdialysis and compared to the effect of SKF 38393 and of LY 171555 selective D1 and D2 dopamine (DA) receptor agonists, respectively. Co-dergocrine (1 and 5 mg kg-1 i.p.) as well as LY 171555 (0.2 and 0.5 mg kg-1 i.p.) decreased the extracellular concentration of ACh in the striatum, whereas SKF 38393 (5 and 10 mg kg-1 i.p.) increased it. On the other hand, Co-dergocrine (1 and 5 mg kg-1), LY 171555 (0.2 and 0.5 mg kg-1) and SKF 38393 (5 and 10 mg kg-1) increased ACh release in the hippocampus in a dose-dependent way. These results show that Co-dergocrine, which is widely used in the treatment of senile mental decline, enhances the release of ACh in the hippocampus in a similar manner to both D1 and D2 DA agonists. This effect might be relevant for the amelioration of cognitive processes. Moreover, our results which demonstrate that Co-dergocrine is able to decrease the release of ACh in the striatum, as are selective D2 agonists, suggest that Co-dergocrine may have a potential therapeutic benefit in Parkinsonian dementia.
Posted 20 November 2004 - 02:53 AM
Int J Clin Pharmacol Ther Toxicol. 1990 Dec;28(12):510-24. Related Articles, Links
On brain protection of co-dergocrine mesylate (Hydergine) against hypoxic hypoxidosis of different severity: double-blind placebo-controlled quantitative EEG and psychometric studies.
Saletu B, Grunberger J, Anderer R.
Division of Pharmacopsychiatry, Psychiatric University Clinic of Vienna, Austria.
Utilizing quantitative EEG and psychometric methods we investigated in two subsequent double-blind, placebo-controlled trials the following questions: 1) Does co-dergocrine mesylate (CDM) protect against cerebral hypoxic hypoxidosis as objectivated by neurophysiological and behavioral measures in man? 2) Does CDM offer protection equally both against moderate and marked hypoxia induced experimentally by inhalation of a gas mixture of 9.8% and 8.6% O2 (equivalent to 6000 m and 7000 m altitude, respectively)? 3) Are brain-protective effects of CDM improving by drug administration over a longer period of time (2 weeks)? In the first study, hypoxic hypoxidosis was induced by a fixed gas combination of 9.8% oxygen and 90.2% N2 (equivalent to 6000 m altitude), which was inhaled for 23 min under normobaric conditions by 15 healthy volunteers. They received randomized after an adaptation session placebo and 5 mg CDM. Blood gases, quantitative EEG, and psychometric measures were obtained under normoxic (21% O2) and hypoxic (9.8% O2) conditions before as well as 2, 4, 6 and 8 h after oral drug administration. Blood gas analysis demonstrated under hypoxia a drop in PO2 from 91 to 37 mmHg and in PCO2 from 38 to 33 mmHg, while pH increased from 7.41 to 7.47. Computer-assisted spectral analysis of the EEG showed an increase of delta/theta, decrease of alpha, and an increase of superimposed fast beta activity indicative of deterioration in vigilance. The latter was documented at the behavioral level by deterioration of intellectual and mnestic functions, psychomotor activity, performance in a reaction time task, mood, and wakefulness. CDM attenuated significantly this brain dysfunction, as it attenuated delta/theta and increased alpha-adjacent beta activity. Psychometric performance based on all 11 variables deteriorated under hypoxia by 49% after placebo, while after 5 mg CDM only by 26%. However, in a subsequent double-blind placebo-controlled trial in 12 healthy young volunteers, further augmentation of hypoxia induced by inhalation of a gas combination of 8.6% O2 and 91.4% N2 (equivalent to 7000 m altitude) leading to a drop of PO2 and PCO2 to 32 and 32 mmHg, respectively and an increase of pH to 7.46 resulted in a loss of brain protection, even when CDM was given over 2 weeks daily. Our findings suggest that treatment of organic brain syndromes with nootropic/antihypoxidotics should be initiated in an early rather than a late stage.
Posted 20 November 2004 - 02:54 AM
Tohoku J Exp Med. 1990 Nov;162(3):225-33. Related Articles, Links
Effects of co-dergocrine mesylate (Hydergine) in multi-infarct dementia as evaluated by positron emission tomography.
Nagasawa H, Kogure K, Kawashima K, Ido T, Itoh M, Hatazawa J.
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Three female patients aged from 74 to 79 with multi-infarct dementia were studied using positron emission tomography (PET) to assess the effect of co-dergocrine mesylate (Hydergine) on cerebral glucose metabolism. The cerebral glucose utilization (CMRGlc) of each patient was evaluated by PET scan using 2-deoxy-[18F]-2-fluoro-D-glucose (FDG). Following the first PET study, 0.04 mg/kg of co-dergocrine mesylate was injected intravenously with 250 ml saline solution, and then the second PET study was performed. The CMRGlc was determined from the images of the PET scan and the radioactivity of 18F in the plasma. After the administration of co-dergocrine mesylate, the value of CMRGlc increased significantly in the cerebral cortex (p less than 0.01 and p less than 0.05) and basal ganglia (p less than 0.05) compared with values before the administration, but no significant increase was found in the centrum semiovale. These results suggest that co-dergocrine mesylate stimulates glucose metabolism of neurons in the human brain.
Posted 20 November 2004 - 02:55 AM
:Arch Int Pharmacodyn Ther. 1989 Jan-Feb;297:225-34. Related Articles, Links
Muscarinic cholinergic receptors in the hippocampus of the aged rat: effects of long-term hydergine administration.
Amenta F, Cavallotti C, Franch F, Ricci A.
Dipartimento di Scienze Neurologiche, Universita "La Sapienza," Rome, Italy.
The effects of senescence and of long-term hydergine treatment on the density and the pattern of muscarinic cholinergic receptors in rat hippocampus were studied using combined radioreceptor binding and autoradiography with [3H]-quinuclidinyl-benzilate ([3H]-QNB) as a ligand. [3H]-QNB accumulated in the hippocampus of 3 month old rats, primarily in the stratum oriens of the CA1 and CA2 fields, followed in descending order by the molecular layer of granule cells of the dentate gyrus and the CA3 field. The density and pattern of [3H]-QNB binding sites in the hippocampus of 16 month old rats were the same. In contrast, the density of [3H]-QNB binding sites in the hippocampus of 22 months old rats was significantly reduced, mainly in the granule cells of the dentate gyrus, next in the CA3 and in the CA1-CA2 fields. Hydergine treatment (0.6 mg/kg and 1 mg/kg, p.o.), started at 16 months of age and continued for 6 months, caused a dose-related restoration of the number of [3H]-QNB binding sites, primarily in the CA1 and CA2 fields and in lesser amounts of the dentate gyrus. The possibility that the therapeutic effects of hydergine administration on memory function in the elderly might be related to an effect on cholinergic muscarinic receptors of the ageing hippocampus is discussed.
Posted 20 November 2004 - 03:18 AM
Posted 20 November 2004 - 04:57 AM
Posted 20 November 2004 - 05:24 AM
Thank you for changing the topic here.
Hydergine FAS tablets should be taken in the morning, with your breakfast. 1 4.5 mg tablet daily should be taken for 3 or more months for the beneficial effects to be clearly seen (or not seen). I have had no adverse effects from Hydergine at all.
Posted 20 November 2004 - 05:45 AM
Posted 20 November 2004 - 03:01 PM
DHA? Where is the best place to get this? I did not see this listed on the Life Extension Foundation site.
VI. DHA IS BRAIN FOOD
Most of the dry weight of the brain is lipid (fat) because brain activity depends greatly upon the functions provided by lipid membranes. Compared to other body tissues, brain content of DHA and arachidonic acid is very high. DHA is particularly concentrated in membranes that are functionally active, namely in synapses and in the retina.
The ability of enzymes to produce the omega-6 and omega-3 family of products of linoleic and alpha-linolenic acid declines with age. One experiment showed that desaturase enzyme function in old rats was only 44% of the desaturase function in young rats [*26]. Because DHA synthesis declines with age, as we get older our need to acquire DHA directly from diet or supplements increases.
Because of the decline in DHA synthesis, it is not surprising that DHA content of brain cell membranes declines. DHA is also reduced when the brains of rats are experimentally exposed to high oxygen levels. Free-radical oxidation probably causes the depletion in both cases. Vitamin E treatment protected the rats from neuron damage from the oxygen. This suggests that Vitamin E may be important for prevention of neurodegeneration in humans [*25].
The greatest dependence on dietary DHA occurs in the foetus during the last third of pregnancy and (to a lesser extent) in the infant during the first 3 months after birth. It is during this period that brain synapses are forming most rapidly, and an infant's demand for DHA exceeds the capacity of the enzymes to synthesize it [*11]. The additional requirements are fulfilled by mechanisms believed to concentrate DHA absorption from the mother's placenta [*12].
After birth, the additional needed DHA comes from the nursing mother. Rapid brain growth in the human infant requires large amounts of omega-3 and omega-6 essential fatty acids. Human milk contains (in total fatty acids by weight) 12% linoleic acid, 0.5% alpha-linolenic acid, 0.6% arachidonic acid and 0.3% DHA [*13]. Infant formulas frequently have not contained arachidonic acid or DHA. One study showed that by (or just before) age 8, children who had been breast-fed as infants had an 8.3-point IQ advantage over children who had received formula [*14]. The study corrected for the education and social class of the mother.
Further support for the idea that DHA is critical for brain development came from an experiment which studied the effects of adding DHA (in the form of fish oil) to infant formula. At both 16 and 30 weeks of age the breast-fed and supplement-formula-fed infants showed significantly better visual acuity than the placebo-formula-fed infants [*15]. Arachidonic acid supplementation is also needed because DHA supplementation given alone lowers arachidonic acid levels [*16] and because arachidonic acid is essential for growth [*17,*18]. Deficiency of arachidonic acid during brain development is less reversible than deficiency of DHA [*19]. Recent reviews have firmly recommended the inclusion of both arachidonic acid and DHA in the formula of premature babies [*20].
Even in the best formulations the efficiency of DHA and arachidonic acid absorption by an infant is inferior to what is seen for breast milk. Therefore, the best way to ensure adequate DHA and arachidonic acid would be for a pregnant/nursing mother to take a DHA supplement. The content of DHA and EPA in human milk has been increased experimentally by giving fish oil supplements to lactating women [*21]. The diet of the mother may contain enough omega-6 fat to allow her to synthesize sufficient arachidonic acid. DHA supplementation would be particularly important for mothers who have consumed excessive alcohol, because alcohol inhibits the desaturase enzymes necessary for DHA synthesis [*22].
Arachidonic acid is similar to glutamate (glutamic acid) in that it can be harmful in conditions of restricted blood circulation (ischemia), but it is essential for normal brain function. It is the EPA (not DHA) in fish oil that can reduce arachidonic acid synthesis. Where pure DHA, rather than fish oil, has been used in infant formulas, inhibition of growth has been much less [*22]. The best infant formula should contain both DHA and arachidonic acid, however, because arachidonic acid improves growth.
An experiment studying maze-learning in rats demonstrated that, after training, the rats showed less cholesterol and more membrane fluidity in the hippocampal and cortical regions of the brain [*23]. Adult mice fed fish oil for 12 months showed more brain DHA, less brain arachidonic acid, more synaptic membrane fluidity and higher maze-learning ability [*24].
Fatty acid in phosphatidylethanolamine of human gray matter cell membrane is roughly 25% DHA, 25% stearic acid, 14% arachidonic and 12% oleic acid. In the outer segments of retina photo-receptors of the eye more than 50% of the fatty acid content is DHA. It is DHA's special properties of permeability and perhaps fluidity that probably accounts for this high concentration [*10].
Epidemiological studies have shown that consumption of DHA is associated with reduced risk of Alzheimer's Disease [ARCHIVES OF NEUROLOGY 60:940-946 (2003)]. DHA has also been shown to induce a 10-fold increase in transcription of the amyloid-ß-scavenger transthyretin [PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (USA) 100(4):1580-1585 (2003)] -- which may explain the part of the protective effect of DHA.
In contemporary diets, omega-6 fatty acids typically exceed all omega-3s (alpha-linolenic, EPA or DHA) by 6 or 7 times. A study on guinea pigs showed that both insufficient and excessive dietary DHA resulted in less than optimal visual acuity. The problems with excessive DHA were attributed to oxidative damage. This result is not too surprising because DHA, with six double-bonds, is the most highly unsaturated fatty acid found in significant quantities in the human body. The researchers did not include Vitamin E in their experiment, which is unfortunate because Vitamin E would be expected to reduce lipid peroxidation [*27]. Nonetheless, another study has shown that DHA reduces lipid peroxidation in the cerebral cortex [*35] (see next section). (return to contents)
VII. OXIDATIVE DAMAGE AND DHA
EPA and DHA are the most unsaturated fatty acids found in large quantities in the bodies of animals and therefore are likely to be more vulnerable to lipid peroxidation than any other fats. Early experiments showed that extremely high levels of cod liver oil in experimental animals can produce enough oxidative damage to result in muscle lesions. Subsequent experiments showed that these lesions can be prevented with vitamin E [*28].
More recent and more careful studies have shown that the oxidative damage due to fish oil -- and the ability to protect against it -- varies greatly between tissues. Vitamin E is least able to protect against oxidation of either EPA or DHA in blood plasma [*29]. The alpha-tocopherol form of vitamin E protects red blood cell membranes of young animals more effectively than those of old animals [*30]. Although both alpha- and gamma-tocopherol protect against lipid peroxidation, they do so by different mechanisms. Generally, gamma-tocopherol is only 30% as effective as the alpha form as an anti-oxidant, but gamma-tocopherol is particularly effective against peroxynitrite [*31].
Alpha-tocopherol protects against oxidative damage from fish oil far more effectively in the liver than in the kidney [*32]. But the kidney is less vulnerable to oxidative damage because kidney cell membrane composition is much less subject to alteration by changes in dietary fat. Although a four-fold increase in alpha-tocopherol above normal dietary levels has been shown to reduce fish oil-induced peroxidation in monkey livers, peroxidation was not completely eliminated. The experimenters suggested that higher levels of vitamin E or other anti-oxidants might reduce the damage further.
Oxidative damage to the heart due to fish oil, however, is much less than oxidative damage to the liver or even the kidney. When incorporated into heart muscle membranes, both EPA and DHA promote alpha-tocopherol being incorporated into the membranes as well. In fact, a high omega-3 fatty acid diet increases the alpha-tocopherol content of heart muscle membranes by five times, and this effect is most prominently associated with DHA [*33,*8].
Vitamin E provides more anti-oxidant benefit to the heart and spleen than selenium, beta-carotene or coenzyme Q10. In fact, at the maximum effective dose of Vitamin E, the other anti-oxidants offer no additional benefit. Selenium, however, gives the most anti-oxidant protection to the kidney. Under certain oxidative stresses coenzyme Q10 gives the most protection to the liver, with little additional benefit from the other anti-oxidants [*34].
DHA's most remarkable effect on oxidation is in the brain, where increasing tissue levels of DHA in the cerebral cortex causes significant increases in the anti-oxidant enzymes catalase, glutathione and glutathione peroxidase -- resulting in decreased cerebral levels of lipid peroxides. The induction of anti-oxidant enzymes by DHA in the brain is so dramatic that the researchers actually referred to DHA as an anti-oxidant [*35]. Although DHA is more readily oxidized than arachidonic acid, arachidonic acid breakdown products (endoperoxides & eicosanoids) generate more free radicals than the products of DHA. DHA also inhibits inhibits inducible nitric oxide synthetase (reducing formation of the peroxynitrite free radical) and inhibits transcription factor NF-KappaB (reducing formation of pro-inflammatory cytokines) [FREE RADICAL BIOLOGY AND MEDICINE 34(8):1006-1016 (2003)].
(return to contents)
VIII. DHA AND IMMUNE FUNCTION
Fish oil has been used for its anti-inflammatory effects in rheumatoid arthritis. Researchers have shown that anti-inflammatory action by DHA (not EPA) helps prevent cardiovascular disease because blood vessel inflammation plays a role in atherosclerosis [*36]. An experiment on human volunteers showed that fish oil concentrate was able to reduce inflammatory cytokines produced from monocytes by at least one third [*37].
The inflammatory response is closely linked to the immune system, and there has been concern that fish oils suppress the immune system along with inflammation. Lipid peroxidation suppresses lymphocyte proliferation, but it has been shown that when adequate amounts of alpha-tocopherol are given with fish oil, lymphocyte proliferation is not reduced [*38]. Fish oil increases the allergenic immunoglobulin IgE, but alpha-tocopherol opposes this increase [*39]. These results indicate that Vitamin E can be used to prevent some of the immune-suppressant effects of fish oil.
Not all of the immune-suppressing effects of fish oil are due to oxidation, however. Incorporation of certain fatty acids into cell membranes affects second-messenger systems (molecular signalling systems within cells) that can modify gene expression. An experiment that studied the individual effects of EPA and DHA found that EPA reduced natural killer (NK) cell activity and cell-mediated immune response, but that DHA does not. This study concluded that the immune-suppressing effects of fish oil are mainly due to EPA, not DHA [*40].
And, as was mentioned in the previous section, DHA reduces the transcription of pro-inflammatory cytokines by NF-KappaB.
(return to contents)
IX. DHA SUPPLEMENTS FOR YOUR HEALTH
Although fish oil has been widely used and widely recommended for its benefits for heart and circulation, DHA is responsible for most of those benefits. Since excessive fish oil can be harmful, it makes sense to maximize the benefits and minimize the hazards by taking DHA rather than fish oil. Is there a supplement offering more benefit to you and your family than one protecting against sudden death due to heart attack -- the number one killer in Western society? DHA provides that benefit, while greatly reducing the hazards of immune-suppression due to EPA.
Mothers in their last third (trimester) of pregnancy or who are breastfeeding a newborn may contribute to the development of their child's brain by taking DHA in consultation with their physician. Others may want to take DHA supplements to guard against the decline of brain DHA normally seen with aging.
Dosages of 6 grams per day of DHA for 120 days have been used by adult males under close bio-medical supervision with no evident side effects [*41]. So 1 or 2 grams of DHA daily should be quite safe for nearly anyone. In comparison with some extremely high dosages of DHA used in animal experiments, 6 grams per day is modest.
But DHA (and fish oil) should be taken with Vitamin E (at least 400 IU), selenium (at least 100 micrograms) and coenzyme Q10 (at least 30 mg) to minimize oxidation. Fish oil is a natural component and health-promoting component of diet, so cautions about oxidation should be heeded in the spirit of avoiding the "more is better" attitude of many people who take supplements. Taken with mindfulness of reducing oxidation, DHA can prevent arrythmia and maintain neural function.
Posted 20 November 2004 - 03:15 PM
Acta Neurol Scand. 1988 Sep;78(3):214-20. Related Articles, Links
Effect of dihydroergotoxine mesylate (Hydergine) on delayed neuronal death in the gerbil hippocampus.
Izumiyama K, Kogure K.
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
The CA 1 neurons in the gerbil hippocampus exhibiting necrosis with delayed onset following 5 min ischemia were reduced markedly by the systemic administration of dihydroergotoxine mesylate (Hydergine; HYG). Immediately after 5 min of forebrain ischemia, the animals were injected intraperitoneally with HYG. Seven days after ischemia, perfusion-fixed brains were processed by conventional histology. The number of neurons per millimeter in the CA 1 pyramidal cell layer were calculated and they were labelled neuronal density. In the control group, the neuronal density was 66.03 +/- 7.37 (mean +/- SEM), in the vehicle group, it was 11.25 +/- 4.93. The neuronal density in the HYG group was 69.19 +/- 6.49. The difference in the neuronal density between the HYG group and the control group was not statistically significant. These data indicate that HYG protects on the CA 1 neurons, and this suggest that the suppression of adrenoceptors by this drugs may be the main mechanism of action. This morphologic outcome may explain the functional amelioration of mental impairment by HYG.
Gerontology. 1988;34(5-6):250-6. Related Articles, Links
Effects of long-term Hydergine administration on lipofuscin accumulation in senescent rat brain.
Amenta D, Ferrante F, Franch F, Amenta F.
Dipartimento di Scienze Neurologiche, Universita La Sapienza, Roma, Italia.
The effects of ageing and of 6 months of Hydergine treatment on lipofuscin deposition within the cytoplasma of pyramidal neurons of rat prefrontal cortex, hippocampus (fields CA1 and CA3) and of Purkinje neurons were assessed microfluorimetrically. No lipofuscin autofluorescence was detected in the nerve cell populations of 3-month-old rats, but lipopigment had accumulated in nerve cell bodies of 16-month-old animals and increased significantly thereafter in rats of 22 months of age. In 22-month-old rats, Hydergine administration (0.6 and 1 mg/kg p.o.) started at 16 months caused a significant dose-related decrease in lipofuscin accumulation within the cytoplasm of the various kinds of nerve cells examined.
Posted 20 November 2004 - 03:19 PM
1: J Gerontol. 1987 Sep;42(5):482-6. Related Articles, Links
The effect of chronic hydergine treatment on the plasticity of synaptic junctions in the dentate gyrus of aged rats.
Bertoni-Freddari C, Giuli C, Pieri C, Paci D, Amadio L, Ermini M, Dravid A.
The number of synapses (Nv), the surface density of contact zones (Sv) as well as the average size (S) of E-PTA stained synapses in the supragranular layer of the dentate gyrus from adult (12 months), old (30 month), and Hydergine-treated old (30 months) rats were measured by using quantitative morphometric techniques. In old animals, Nv and Sv were significantly reduced, whereas S was significantly increased as compared with the values in adult rats. Hydergine (Codergocrine mesylate) treatment of old animals (3 mg/Kg/day for 4 weeks) influenced these three parameters, differentially. The Sv in aged animals receiving Hydergine, relative to that in untreated old rats, was significantly increased; the number and size of synapses in the treated old rats were significantly higher and smaller, respectively, than that in old controls. We interpret the present findings to indicate a modulating effect of Hydergine on the morphological plasticity of synaptic junctions in the dentate gyrus of aged rats.
J Pharmacol. 1985;16 Suppl 3:57-63. Related Articles, Links
Learning and cholinergic neurotransmission in old animals: the effect of Hydergine.
[Article in English, French]
Le Poncin-Lafitte M, Rapin JR, Duterte D, Galiez V, Lamproglou I.
In the present work, a study of the number of functional receptors has been made with 3HQNB given to resting awaken animals during a learning process. Ageing leads to a decrease in the ability of learning associated with an increase in the number of large movements. The number of cholinergic receptors is also reducel if we compare 22 month old animals with 4 month old animals maintained under usual conditions. Learning conditioning leads to a stimulation of the cholinergic system with a release of acetylcholine. The mediator takes the 3HQNB out of its fixation areas which causes an apparent decrease in the number of receptors. This result is more significant in young animals than in aged ones because of the possibility of activation in the cholinergic system. The treatment by dihydroergotoxine partially re-establishes the learning abilities in animals and, at the same time, increases the number of cholinergic receptors This effect could explain the actions of this drug on the memory process in ageing persons.
Pharmacol. 1985;16 Suppl 3:33-8. Related Articles, Links
A modulating effect of Hygergine on the synaptic plasticity of old rats.
[Article in English, French]
Bertoni-Freddari C, Giuli C, Pieri C, Paci D, Dravid A.
The morphological plasticity of E-PTA stained synaptic junctions was investigated by means of quantitative morphometry in the dentate gyrus supra-granular layer of adult, old and old-Hydergine treated rats. Numerical (Nv) and surface (Sv) density as well as average size of the synapses (S) were the three parameters considered. During aging, Nv and Sv significantly decrease whereas S increases. Hydergine treatment to old rats resulted in a significant increase of Nv and Sv and a significant decrease of S. Present findings are interpreted as a modulating effect of Hydergine on the synaptic plasticity of old rats.
Posted 21 November 2004 - 05:18 AM
Aaahem,
Hey Nootropi,
whaddup with the really big letters? I said my eyesight was getting poorer, I didn't say I was getting blind. [lol]
Just kidding
Posted 21 November 2004 - 03:47 PM
Very funny. I thought it would simplify your reading if I was to increase the font to a larger size. Also: these results are very compelling, don't you agree?
Posted 21 November 2004 - 04:03 PM
Has anyone ever figured out what percentage of rat trials successfully transfer their results over to human trials, especially ones involving chemicals that affect the brain?
The rats help themselves to the drug, which is available to them for two hours a day for two weeks. Rats are used because their behaviour, particularly in memory tasks, is similar to human behaviour. Rats which had taken the drug performed poorly on memory tests, such as choosing levers, and the ones that were "loaded" on high levels of Ecstasy displayed "serotonin syndrome", behaviour, which included head-weaving or lying flat out on the ground.
Because this theory cannot be tested on humans, researchers must use rats. Adolescent rats are used because like human adolescents they spend more time in social interactions than the younger and the older animals. Adolescent humans and rats also show comparable behavioral, hormonal and brain changes, and these similarities will allow researchers to investigate alcohol effects on social behavior and motivation for social contacts.
Posted 03 December 2004 - 05:46 AM
Posted 03 December 2004 - 12:05 PM
Posted 04 December 2004 - 05:49 PM
Also, if you have a good hippocampus, you got a great memory. It is used in creating new long term memories.
...I should add that in the movie Memento, Guy Pierce could not remember a darn thing because he had his hippocampus removed.
Some new drugs in trials focus on this. (Newsweek Dec 6, 2004)
http://www.apex.net....es/memento.html
Posted 11 December 2004 - 04:01 PM
Here is another interesting article that asserts that "Chronic dihydroergotoxine administration increases muscarinic cholinergic receptor binding in aged-rat brain."
dihydroergotoxine= hydergine = DHET
Res Commun Chem Pathol Pharmacol. 1987 Aug;57(2):149-59.
Chronic dihydroergotoxine administration increases muscarinic cholinergic receptor binding in aged-rat brain.
Ogawa N, Mizukawa K, Sora I.
Institute for Neurobiology, Okayama University Medical School, Japan.
Changes in the distribution and densities of muscarinic cholinergic receptors (mCh-R) and the effects of dihydroergotoxine (DHET) administration on these changes were studied in the aged-rat brain by in vitro autoradiography. mCh-R binding in the brain was markedly reduced in aged rats as compared with young adult rats, but chronic administration of DHET specifically recovered mCh-R binding in the temporal cortex and hippocampus.
PMID: 3659567 [PubMed - indexed for MEDLINE]
Posted 11 December 2004 - 05:43 PM
Heh, no answer for the vasopressin/desmopressin inquiry, eh?
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