Dynorphin A-(1-13) attenuates basal forebrain-lesion-induced amnesia in rats

The effects of dynorphin A-(1-13), an endogenous kappa opioid agonist, on basal forebrain (BF)-lesion-induced amnesia in rats were investigated using step-through-type passive avoidance task. The BF was lesioned by injecting the cholinergic neurotoxin ibotenic acid (6 micrograms/side). The number of rats achieving the cut-off time (600 s) of step-through latency (STL) in BF-lesioned group significantly decreased as compared with that in sham-operated group. Dynorphin A-(1-13) (0.3 micrograms) significantly increased the number of rats achieving the cut-off time of STL in BF-lesioned rats. These results suggest that dynorphins play an improving role in the impairment of memory processes in BF-lesioned rats.     

Ganglioside GM1 protects cAMP 3'5':phosphodiesterase from inactivation caused by lipid peroxidation in brain synaptosomes of rats

The preincubation of synaptosomes with nanomolar concentrations of ganglioside GM1 was shown to protect Ca(2+)-dependent and Ca(2+)-independent cyclic nucleotide phosphodiesterase from inactivation caused by lipid peroxidation (LPO) induction. Thus, Ca(2+)-dependent phosphodiesterase activity decreased to approximately 34% of the initial value following 30 min of LPO induction, but it constituted more than 60% of the control activity if synaptosomes were preincubated with 10(-8)M GM1, the difference being statistically significant. 10(-6)M alpha-tocopherol had a similar effect. As far as the lipid matrix is concerned, gangliosides were found to prevent to a great extent malonic dialdehyde (MDA) accumulation and to protect polyenoic fatty acids from oxidative destruction. The ability of gangliosides to protect phosphodiesterase from inactivation caused by LPO induction appears to be owing not only to the inhibition of the accumulation of LPO products, but to the direct activation of the enzyme as well, 10(-7) M of ganglioside GM1 having the maximal activating effect. In contrast to alpha-tocopherol and other antioxidants reacting directly with free radicals, the inhibitory effect of gangliosides appears to be mediated by signal transduction systems.     

GM1 ganglioside attenuates the development of vacuous chewing movements induced by long-term haloperidol treatment of rats

Tardive dyskinesia (TD) is a serious side-effect of long-term treatment with neuroleptics. To investigate if TD may be a result of neuroleptic-induced excessive stimulation of striatal glutamate receptors, the effect of the anti-excitotoxic GM1 ganglioside was studied in a rat model of TD. In an acute experiment each of four groups of rats was treated with GM1 20 mg/kg SC+saline IP, saline SC+haloperidol 1.2 mg/kg IP, GM1 SC+haloperidol IP, or saline SC+saline IP. In a subsequent long-term experiment lasting 16 weeks, each of the four groups was treated as in the acute experiment, with the exception that haloperidol was injected IM as decanoate 38 mg/kg every 4 weeks, and the controls received vehicle injections. The behavior was videotaped and scored at intervals during both experiments, including 16 weeks after cessation of the long-term treatment. Haloperidol induced a significant increase in vacuous chewing movements (VCM) and immobility both in the acute and in the long-term experiment. Other categories of behaviour (rearing, moving, sitting) were significantly affected only in the acute experiment. GM1 did not affect any of the acute behavioural effects of haloperidol, but significantly reduced VCM in the long-term experiment. The effects on VCM of haloperidol and GM1 persisted for at least 8 weeks after cessation of the long-term treatment. These results suggest that long-lasting changes in striatal function induced by excessive glutamate receptor stimulation may be a mechanism for the development of VCM in rats and perhaps also for TD in humans.     

Ganglioside GM2 is substrate for a sialidase in MDCK cells

GM1 ganglioside carrying a fluorescent fatty acid in substitution of the natural one, has been administered to cultured Madin-Darby canine kidney (MDCK) cells for different pulse times (0.5-24 h), and its metabolic fate was followed. The fluorescent GM2, asialo-GM2, asialo-GM1 and ceramide were the only detectable metabolites. The complete absence of fluorescent GM3 is consistent with the presence in these cells of a sialidase working on GM1 and GM2 gangliosides. After treatment of the cells with chloroquine the fluorescent GM1 remained essentially undegraded, indicating a catabolic processing at lysosomal level.     

Ganglioside GM1 enhances induction by nerve growth factor of a putative dimer of TrkA

GM1 enhances nerve growth factor (NGF)-stimulated neuritogenesis and prevents apoptotic death of PC12 cells; both may be due to enhancement of TrkA dimerization. In this study, we examined the effect of GM1 on NGF-induced TrkA dimerization in Trk-PC12 (6-24) cells. NGF increased tyrosine phosphorylation of the 140-kDa protein (TrkA monomer), and preincubation with GM1 potentiated this effect. Adding the protein cross-linker bis(sulfosuccinimidyl) suberate with NGF resulted in the appearance of two major bands (220 and 330 kDa) when probed with antibodies against TrkA or phosphotyrosine, and GM1 also enhanced this effect. We interpret the 330-kDa band as being a homodimer of TrkA. The identity of the 220-kDa band is still not certain but may consist of a posttranslationally modified form of TrkA. Our results suggest that GM1 is augmenting the effects of NGF on PC12 cells by enhancing the dimerization and activation of the TrkA receptor.     

Cue-dependent amnesia in rats.

Gave 78 male Sprague-Dawley rats extensive training in a complicated appetitive maze. Following a retention interval of 7 days, Ss were given a single ECS. Ss for which memory cues had been reinstated just prior to ECS were more amnesic upon retest than Ss whose memories had not been reinstated. Thus, amnesia can be produced for well-established memories if the memory cues are present at the time the amnesic agent occurs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ipidacrine (NIK-247), a novel antidementia, rapidly enters the brain and improves scopolamine-induced amnesia in rats during the Morris water maze task

The effects of single and repeated administrations of ipidacrine (NIK-247, 9-amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b] quinoline monohydrochloride monohydrate) on scopolamine-induced spatial learning deficit were investigated in rats using the Morris water maze task. A single oral administration of ipidacrine (0.3 and 1 mg/kg) reduced the increased total latency induced by scopolamine in this task. The repeated administration of ipidacrine (1 mg/kg) of once a day for 5 successive days reduced the increased total latency induced by scopolamine to the levels of the saline-treated control rats in this task. In this pharmaco-kinetic study, ipidacrine was rapidly taken up into the brain within 5 min. Moreover, higher drug levels were observed mainly in the cortex and hippocampus, which both play important roles in learning and memory. Thus, a previous study together with this investigation indicate that ipidacrine improves amnesia which consists of the impairment of the working and reference memory in various animal models, suggesting that ipidacrine is a useful candidate for the therapy of patients with Alzheimer's disease.     

Temporal aspects of scopolamine-induced one-way memory dissociation in mice.

Conducted 4 experiments, using a total of 482 Swiss Webster mice which were trained in a single session on an object-discrimination shock-escape task after ip injection of scopolamine (1.2 mg/kg) or saline. They were subsequently required to relearn the task after 1, 2, or 4 days, with half the Ss receiving the same agent as on training, the other half receiving the opposite agent. Results from the 2-day study support a dual-effect model of 1-way dissociation, which postulates 2 actions of the drug: (a) a reduction in learning efficiency and (b) scopolamine state dependency. However, the pattern of results for the 1-day study showed a much attenuated state-dependency effect, while the 4-day groups showed no significant intergroup differences, violating both postulates. It is suggested that 1-way memory dissociation, and specifically the concept of state dependence, be reconsidered in terms of the temporal aspects of the memory process. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ganglioside GM1 activates the mitogen-activated protein kinase Erk2 and p70 S6 kinase in U-1242 MG human glioma cells

Gangliosides are implicated in the regulation of cellular proliferation as evidenced by differences in ganglioside composition associated with malignant transformation and density of cells in culture, as well as their inhibitory effects when added to cells growing in culture. Exogenously added gangliosides have a bimodal effect on proliferation in U-1242 MG glioma cells, inhibiting DNA synthesis in growing cells and stimulating it in quiescent cells. We investigated the mechanisms involved in stimulation of DNA synthesis using [3H]thymidine incorporation and immune complex kinase assays to identify responsible signal transduction pathways. Treatment of quiescent U-1242 MG cells with GM1 caused activation of the mitogen-activated protein (MAP) kinase isoform Erk2. Pretreatment with the specific MAP kinase kinase inhibitor PD98059 prevented the GM1-stimulated Erk2 activation and GM1-stimulated DNA synthesis. GM1 treatment stimulated another distinct signaling pathway leading to activation of p70 S6 kinase (p70s6k), and this was prevented by pretreatment with rapamycin. Rapamycin also inhibited GM1-stimulated DNA synthesis. Activation of both pathways and stimulation of DNA synthesis were inhibited by forskolin treatment; however, GM1 had no effect on cyclic AMP levels. Platelet-derived growth factor also activated both Erk2 and p70s6k but did not cause DNA synthesis, suggesting that GM1 may stimulate additional cascades, which also contribute to GM1-mediated DNA synthesis.     

Effect of ganglioside (GM1) on memory in senescent rats

We investigated the effects of aerosolized prostacyclin (PGI2) administration on hemodynamics and pulmonary gas exchange in 8 patients with severe respiratory failure and acute pulmonary hypertension. Nebulization of epoprostenol (5 ng/kg body weight for 15 min) decreased mean pulmonary blood pressure from 41.2 +/- 6.7 mm Hg (mean +/- SD, before administration) to 36.1 +/- 6 mm Hg < or = 15 min (p < 0.05). The effect was reversed 10 min after discontinuation of PGI2 (40.9 +/- 6.3 mm Hg). Pulmonary vascular resistance index (339 +/- 138 dynes.s.cm-5.m2, before administration) was significantly (p < 0.05) reduced < or = 15 min (260 +/- 89 dynes.s.cm-5.m2) and increased again after discontinuation of PGI2 (341 +/- 142 dynes.s.cm-5.m2). The ratio of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) increased from 119 +/- 34 mm Hg (before administration) to 163 +/- 76 mm Hg (15 min after initiation of administration p < 0.05) and was reduced after PGI2 discontinuation (116 +/- 35 mm Hg). Heart rate, mean blood pressure, central venous pressure, and pulmonary arterial wedge pressure remained unchanged, whereas cardiac index was slightly reduced. We assume that PGI2 aerosolization is a beneficial technique, applied with a ventilator nebulization system. The beneficial effect might be caused by selective pulmonary vasodilatation in well-ventilated areas of the lung.     

Cycloheximide-induced amnesia for taste aversion memory in rats

The presence of S-sulphocysteine in filtrates of the dermatophyte Keratinomyces ajelloi growing on human hair in a culture medium buffered by pH 7-4 by phosphates was demonstrated by means of ion exchange chromatography techniques. S-sulphocysteine being destroyed during acidic hydrolysis was identified after enzymic hyrolysis of dialyzed and lyophilized filtrates. This result indicates that sulphitolysis occurs during kerationlysis performed by K. ajelloi. As thiosulphuric esters were shown present in hair perforations made by Microsporum gypseum, we think sulphitolysis is a common mechanism developed by dermatophytes to attack keratin.     

Anterograde amnesia induced by hyperthermia in rats.

Anterograde amnesia (AA), forgetting of events that occur following a traumatic episode, has recently been demonstrated by using hypothermia as the amnestic agent. However, no data currently exist to indicate if hyperthermia might affect memory processing in a similar manner. Experiments 1 and 2 demonstrated that increasing the colonic body temperature of the rat to 3–4°C or more above normal during avoidance training, produced a significant retention loss when the test occurred 24 hr after training. In Experiment 3, AA resulting from an elevation in temperature was reversed by reheating "amnestic" subjects just prior to the 24-hr test. By rapidly reversing hyperthermia immediately after the training trial with a cooling procedure, Experiment 4 demonstrated that hyperthermia-induced AA was not the result of retrograde influences of the heating treatment. Results are discussed in terms of possible retention deficits which could conceivably follow environmental heat stress or fever hyperthermia resulting from bacterial infection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

State-dependent models of ECS-induced amnesia in rats.

Conducted 3 experiments with a total of 220 male albino Sprague-Dawley rats, to investigate 2 state-dependent hypotheses which state that ECS-induced amnesia occurs when (a) the physiological state during testing is dissimilar from that during training (regardless of when consolidation occurs), or (b) the state at testing differs from that during consolidation (consolidation is assumed to occur after ECS). Data were gathered in a 1-trial passive-avoidance apparatus, and amnesia as a function of states during acquisition, consolidation, and testing was examined. Exp. I failed to support the train-test, state-dependent position. Exp. II produced data consistent with the consolidate-test, state-dependent position, but Exp. III found that the consolidate-test, state-dependent data were confounded by an induced recovery effect independent of S's physiological state at the time of testing. Although inconsistent with either of the state-dependent hypotheses, data support a retrieval-failure view of experimental amnesia. (24 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Testosterone potentiates scopolamine-induced disruptions of nonspatial learning in gonadectomized male rats.

Whereas research into the effects of the gonadal hormones on learning and memory has primarily focused on estrogen in females, recent evidence suggests that testosterone can also modulate learning in males through an interaction with the cholinergic system. In the present study, the interactive effects of testosterone and scopolamine (0.1- 0.32 mg/kg), a muscarinic receptor antagonist, on complex behavioral processes were investigated in male rats trained to respond under a multiple schedule of repeated acquisition and performance. In the acquisition component, subjects acquired a different 3-response sequence each session, whereas in the performance component, they responded on the same 3-response sequence each session. Although gonadectomy did not disrupt responding in either component, gonadectomized rats were less sensitive to the disruptive effects of scopolamine on both response rate and accuracy. In contrast, after receiving exogenous testosterone replacement, these gonadectomized males were more sensitive to the behavioral disruptions produced by scopolamine (i.e., the effects of scopolamine were similar to those obtained in gonadally intact males). These results suggest that testosterone replacement can enhance scopolamine-induced behavioral effects in gonadectomized male rats responding under a multiple schedule of repeated acquisition and performance, a finding that is in contrast to those previously found for certain spatial tasks. Furthermore, the present findings suggest that testosterone may decrease the activity of the cholinergic system during nonspatial tasks and thereby work in concert with the antagonism produced by scopolamine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The modulation by neurosteroids of the scopolamine-induced learning impairment in mice involves an interaction with sigma1 (sigma1) receptors

Pulmonary tuberculosis: primary tuberculosis, usually asymptomatic, represents the first infection and is shown by a parenchymal mostly mid-pulmonary focus and satellite lymphadenopathy. Postprimary pulmonary tuberculosis, mostly located in the upper fields may be caused by endogenous reinfection for reactivation of a hematogenous focus formed during primary infection or from exogenous reinfection. Extrapulmonary tuberculosis: it includes numerous forms mostly from hematogenous spread. Miliary tuberculosis may involve a number of organs and apparatus besides the lung. Tuberculous meningitis predominantly involves the base of the skull, the fluid is clear with hypoglycorrhachia and lymphocyte pleocytosis. Lymph node tuberculosis is generally unilateral and cervical. Tuberculous pleuritis is exudative or dry. Other forms of tuberculous serositis are pericarditis and peritonitis. Renal tuberculosis involves the medullaris and intestinal tuberculosis the ileocecum; tuberculous spondilitis (Pott's disease) involves the last dorsal vertebrae. Other forms are osteoarthritis, genital tract tuberculosis, pancreatitis, laryngitis, otitis.     

Source of cues for cue-dependent amnesia in rats.

In 2 experiments 54 Sprague-Dawley male albino rats were given extensive training in a complicated appetitive maze and then handled extensively for 7 days. On the 7th day of the retention interval some Ss were exposed to the "cognitive" learning cues of the maze and some were not. Immediately afterward Ss were given ECS or sham ECS. To the extent that cognitive learning cues are assumed to activate memory, the ECS impaired retrieval of memory only for those Ss which had the cues reinstated prior to ECS administration. It appears that memory must be active at the time of ECS in order to obtain retrieval deficits. In a 3rd experiment with 36 Ss the intensity of hunger drive, manipulated by the amount of prefeeding, was not a cue for memory activation and subsequent cue-dependent amnesia. Arousal is therefore not believed to be crucial for the effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

GM1 increases the content and mRNA of NGF in the brain of aged rats

Aged (20-22 months old) and young (3 months old) Sprague-Dawley rats were treated with GM1 ganglioside, 30 mg/kg i.p. for 30 days, and the content of nerve growth factor (NGF) and the high-affinity tyrosine receptor kinase (Trk) examined. NGF, estimated by a two-site enzyme immunoassay, was found moderately decreased in the frontal cortex and hippocampus, but not in the striatum of aged animals compared with young animals. The NGF decrease was accompanied by a reduction of NGF mRNA, evaluated by northern blot. Trk protein, determined by western blot with a pan-Trk antibody, was not altered in any region studied in the aged brain. GM1 treatment partially restored NGF and NGF mRNA in frontal cortex and hippocampus in the aged brain, but treatment had no effect on Trk protein. GM1 did not modify any of the parameters investigated in young animals.     

Attenuation of cycloheximide-induced amnesia in mice with strychnine sulfate.

Conducted 2 experiments to determine the effectiveness of strychnine sulfate in attenuating the amnesia induced in mice by small doses of cycloheximide (CYC). Previously, reversal of CYC-induced amnesia by catecholamine agonists has been taken as evidence that protein synthesis inhibitors induce amnesia via an inhibition of catecholamine synthesis. In Exp I, 220 male C57/BL 6J mice (aged 8–20 wks) were taught passive avoidance and received injections of saline, strychnine sulfate, or dextroamphetamine sulfate posttraining. Exp II was conducted with 18 Ss and a larger dose of CYC. Results of Exp I show that strychnine sulfate attenuated an amnesia induced by 30 mg/kg CYC, and the results of Exp II show that even the robust amnesia induced by 75 mg/kg CYC could be attenuated by strychnine sulfate. Results concur with previous experiments that show that agents having little or no effect on the catecholamines can nonetheless attenuate amnesia induced by the protein synthesis inhibitors. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Estradiol replacement in gonadectomized male rats alters scopolamine-induced disruptions of nonspatial learning.

Recent evidence indicates that testosterone can modulate learning in males through an interaction with the cholinergic system. However, the mechanism for this interaction between testosterone and the cholinergic system on learning remains uncharacterized and may involve several of testosterone's active metabolites. In the present study, two of the active metabolites of testosterone, 5α-dihydrotestosterone and estradiol, were administered in combination with the muscarinic receptor antagonist scopolamine (0.1-1 mg/kg, i.p.) to adult gonadectomized male rats that were trained to respond under a multiple schedule of repeated acquisition and performance of response sequences. In the acquisition component, subjects acquired a different three-response sequence each session, whereas in the performance component they responded on the same three-response sequence each session. When scopolamine was administered, it produced greater rate-decreasing and error-increasing effects in gonadally intact subjects than in gonadectomized subjects, even though gonadectomy had little or no effect on these measures under control conditions. In gonadectomized rats receiving 5α-dihydrotestosterone replacement, the disruptions produced by scopolamine were also smaller than those produced in gonadally intact subjects. In contrast, gonadectomized rats receiving estradiol replacement were as sensitive, or more sensitive, to scopolamine-induced disruptions of response rate and accuracy than those under the gonadally intact condition. These results suggest that testosterone's interactive effects with the cholinergic system on learning in gonadectomized male rats may not be mediated directly via androgen receptors, but rather by estrogen receptors following the aromatization of testosterone to estradiol. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preventing and alleviating hypothermia-induced amnesia in weanling and young adult rats.

Reminder (Experiment 1) and familiarization (Experiment 2) treatments were found to have similiar effects on the 24-hr retention performance of 24- to 26- and 90- to 100-day-old rats that either did or did not undergo an amnesic treatment (hypothermia) immediately after training. Similar degrees of retrograde amnesia and normal forgetting were evident in both trained age groups that were not subjected to familiarization or reminder treatments. These results suggest that memory processes in weanling and adult rats are similar in susceptibility to disruption by an established amnesic treatment (hypothermia) and in the ease of prevention of and recovery from amnesia by recognized preventive (familiarization) and alleviation (reminder) measures. The similarity of the effects of these preventive and alleviation treatments on normal forgetting and induced amnesia suggests that experimentally induced amnesia may be a fruitful approach to studying the ontogeny of memory processes and, more specifically, to studying factors that influence infantile amnesia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)