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At least 865 records · Page 48Linked to original sources
PubMed1999

Reduced mastication stimulates impairment of spatial memory and degeneration of hippocampal neurons in aged SAMP8 mice.

The involvement of reduced mastication in senile dementia was evaluated by examining the effect of cutting off the upper molars (molarless) on spatial memory and numbers of hippocampal neurons in aged SAMP8 mice. Molarless mice showed a decrease in both learning ability in a water maze and neuron density in the hippocampal CA1 region compared with control mice. These changes increased the longer the molarless condition persisted. The data suggest a possible link between reduced mastication and hippocampal neuron loss that may be one risk factor for senile impairment of spatial memory.

Aging↗
PubMed2001

Neurotoxicological effects associated with short-term exposure of Sprague-Dawley rats to hydrogen sulfide.

Although hydrogen sulfide (H2S) is a known neurotoxic hazard, only a limited number of experimental animal studies have examined its neurochemical or behavioral effects. Our aim was to determine if short-term inhalation exposure of rats to H2S would result in altered brain catecholamnine levels or impaired learning and memory. Three groups of adult male CD rats were tested; two groups were exposed by nose-only inhalation (0, 30, 80, 200, or 400 ppm H2S) and one group was exposed by whole-body inhalation (0, 10, 30, or 80 ppm H2S) for 3 h per day forfive consecutive days. The first group (n = 10 rats per concentration) was tested immediately following each daily nose-only H2S exposure for spatial learning with a Morris water maze. Core body temperatures were also monitored in these animals during and after the last H2S exposure. The second group of rats (n = 10 rats per concentration) was tested for spontaneous motor activity immediately following the fifth exposure. These rats were then euthanized and striatal, hippocampal, and hindbrain catecholamnine levels determined. A third group of rats (n = 5-7 rats per concentration) was pretrained on a multiple fixed- interval (FI) schedule and exposed whole-body. Daily performance on the FI schedule was compared for the week pre-exposure, for the exposure week immediately following daily exposures, and for the week postexposure. We observed significant reductions in motor activity, water maze performance, and body temperature following exposure only to high concentrations (> or = 80 ppm) of H2S. Exposure to H2S did not affect regional brain catecholamine concentrations or performance on the FI schedule. Additional studies using other measures of behavior and longer-term exposure to H2S may be required to more definitively address conditions under which H2S exposure results in behavioral toxicity.

Administration, Inhalation↗
PubMed2000

Auditory cues support place navigation in rats when associated with a visual cue.

Rats, like other crepuscular animals, have excellent auditory capacities and they discriminate well between different sounds [Heffner HE, Heffner RS, Hearing in two cricetid rodents: wood rats (Neotoma floridana) and grasshopper mouse (Onychomys leucogaster). J Comp Psychol 1985;99(3):275-88]. However, most experimental literature concerning spatial orientation almost exclusively emphasizes the use of visual landmarks [Cressant A, Muller RU, Poucet B. Failure of centrally placed objects to control the firing fields of hippocampal place cells. J Neurosci 1997;17(7):2531-42; and Goodridge JP, Taube JS. Preferential use of the landmark navigational system by head direction cells in rats. Behav Neurosci 1995;109(1):49-61]. To address the important issue of whether rats are able to achieve a place navigation task relative to auditory beacons, we designed a place learning task in the water maze. We controlled cue availability by conducting the experiment in total darkness. Three auditory cues did not allow place navigation whereas three visual cues in the same positions did support place navigation. One auditory beacon directly associated with the goal location did not support taxon navigation (a beacon strategy allowing the animal to find the goal just by swimming toward the cue). Replacing the auditory beacons by one single visual beacon did support taxon navigation. A multimodal configuration of two auditory cues and one visual cue allowed correct place navigation. The deletion of the two auditory or of the one visual cue did disrupt the spatial performance. Thus rats can combine information from different sensory modalities to achieve a place navigation task. In particular, auditory cues support place navigation when associated with a visual one.

Animals↗
PubMed2003

A heparin derived oligosaccharide normalizes the fear response of old Brown Norway rats.

Old animals exhibit impaired spatial learning and an exaggerated response to stress. It was predicted that the heparin derived oligosaccharide (HDO), C3, would reverse these age-related deficits. Young (4-5 months) and old (19-20 months) Brown Norway male rats ingested C3 (25 mg/kg per day, p.o.) or vehicle (drinking water) daily for 42-44 days. Two weeks after the initiation of drug treatment, the rats were examined using a series of behavioral tests. The old control rats evidenced: (1) increased neophobia and reduced exploratory behavior in a novel open field (OF); and (2) exaggerated freezing during the acquisition and retention of a conditioned response (CR) to a Pavlovian light-shock pairing ("foreground" conditioning). C3 treatment attenuated or reversed this age-related impairment of emotional behavior. Analysis of spatial learning using the Morris water maze (MWM), and of CR formation to the place in which the foreground conditioning was conducted ("background" conditioning) during context dependent fear conditioning (CDFC) did not reveal major age or drug effects on memory processes. It is hypothesized that C3 repairs damage to the extracellular matrix (ECM) that occurs during the aging process and thereby normalizes age-related exacerbated fear behaviors without affecting mnestic processes.

Aging↗
PubMed1998

Neuronal and behavioral differences between Mus musculus domesticus (C57BL/6JBy) and Mus musculus castaneus (CAST/Ei).

Previous studies have demonstrated that classical inbred strains of laboratory mice do not exhibit large genetic distances when simple sequence repeats (SSRs) are used to test for their polymorphisms whereas mice from wild origin exhibit high polymorphisms (more than 90%) for these sequence when compared with classical inbred strains of laboratory mice. The difference between Mus musculus castaneus and C57BL/6J reaches 98% and F1s male and female are fertile. These two properties pave the way for gene mapping derivating segregating generations between these strains. The phenotypical characteristics of Mus musculus castaneus have not been investigated, unfortunately. The first screening of Mus musculus castaneus and C57BL/6By was carried out for sensorial and motor development, spontaneous behavior in new environment, paw preference, maternal behavior, aggression in two different situations and time to learn escape in a water maze. Morphometry of hippocampus and weight of the male reproductive organs for measures that have been reported to be correlated with several of the examined behavior are also reported. The authors tested also reactivity to one drug (beta-CCM) revealing seizure proneness. The two strains differ for 69% of the reported measures. Comparison to other strains for the same measures obtained in the laboratory for identical tests with mice reared in identical situations provided the mean to compare Mus musculus castaneus with a large set of more or less traditional mice. This strain has the most extreme position for 80% of the comparisons.

Aggression↗
PubMed2000

Impairment of spatial memory and changes in astroglial responsiveness following loss of molar teeth in aged SAMP8 mice.

In order to evaluate the mechanism(s) responsible for senile impairment of cognitive function as a result of reduced mastication, the effects of the loss of the molar teeth (molarless condition) on the hippocampal expression of glial fibrous acidic protein (GFAP) and on spatial memory in young adult and aged SAMP8 mice were studied using immunohistochemical and behavioral techniques. Aged molarless mice showed a significantly reduced learning ability in a water maze test compared with age-matched control mice, while there was no difference between control and molarless young adult mice. Immunohistochemical analysis showed that the molarless condition enhanced the age-dependent increase in the density and hypertrophy of GFAP-labeled astrocytes in the CA1 region of the hippocampus. These effects increased the longer the molarless condition persisted. When the extracellular K+ concentration ([K+]o) was increased from 4 to 40 mM for hippocampal slices in vitro, the mean increase in the membrane potential was about 57 mV for fine, delicate astrocytes, the most frequently observed type of GFAP-positive cell in the young adult mice, and about 44 mV for the hypertrophic astrocytes of aged mice. However, there was no significant difference in resting membrane potential between these cell types. The data suggest that an impairment of spatial memory and changes in astroglial responsiveness occur following the loss of molar teeth in aged SAMP8 mice.

Aging↗
PubMed1999

Effects of chronic lead (Pb) exposure on neurobehavioral function and dopaminergic neurotransmitter receptors in rats.

Sprague-Dawley rats were maternally and permanently exposed to Pb (1000 ppm in their drinking water as lead acetate). Behavioral functions were examined starting at post-natal day (PN) 84. Lead exposure did not change spatial learning in the radial arm maze, but induced higher locomotor activity as observed in the open-field and in the radial arm maze. Lead treatment did not impact motor coordination. Autoradiographic analysis of brain sections indicated that Pb-exposure did produce a decrease in [125I]sulpride (D2 receptor antagonist) binding in the cerebral cortex, but not in the striatum and thalamus nucleus. No change was found in [125I]SCH-23982 (D1 receptor antagonist) binding. Since the cortical dopaminergic system is critical for cognitive processes and motor behavior, it is possible that Pb-related change in D2 receptors may mediate to it induced hyperlocomotor activity.

Animals↗
PubMed1996

Deficient plasticity in the primary visual cortex of alpha-calcium/calmodulin-dependent protein kinase II mutant mice.

The recent characterization of plasticity in the mouse visual cortex permits the use of mutant mice to investigate the cellular mechanisms underlying activity-dependent development. As calcium-dependent signaling pathways have been implicated in neuronal plasticity, we examined visual cortical plasticity in mice lacking the alpha-isoform of calcium/calmodulin-dependent protein kinase II (alpha CaMKII). In wild-type mice, brief occlusion of vision in one eye during a critical period reduces responses in the visual cortex. In half of the alpha CaMKII-deficient mice, visual cortical responses developed normally, but visual cortical plasticity was greatly diminished. After intensive training, spatial learning in the Morris water maze was severely impaired in a similar fraction of mutant animals. These data indicate that loss of alpha CaMKII results in a severe but variable defect in neuronal plasticity.

Animals↗
PubMed2003

Motor coordination, exploration, and spatial learning in a natural mouse mutation (nervous) with Purkinje cell degeneration.

The nervous mouse mutation causes a relatively selective degeneration of Purkinje cells in the cerebellar cortex. The mutants were compared to age-matched controls of the same background strain in tests of motor activity and coordination, spontaneous alternation, and spatial learning in the Morris water maze. As expected from their ataxia, the nervous mutants were impaired in stationary beam, coat-hanger, and rotorod tests of motor coordination. The nervous mutants were also impaired in the submerged but not in the visible platform condition of the Morris water maze, attributable to a spatial deficit, and displayed a higher level of motor activity in an automated chamber. The deficit in spontaneous alternation rates seen in nervous mutants is accountable by reduced motivation, disinhibition, or spatial disorientation.

Analysis of Variance↗
PubMed2005

Loss of the limbic mineralocorticoid receptor impairs behavioral plasticity.

Corticosteroid action in the brain is mediated by the mineralocorticoid (MR) and the glucocorticoid (GR) receptor. Disturbances in MR- and GR-mediated effects are thought to impair cognition, behavior, and endocrine control. To assess the function of the limbic MR in these processes, we inactivated the MR gene in the forebrain of the mouse using the Cre/loxP-recombination system. We screened the mice with a limbic MR deficiency in various learning and exploration tests. The mutant mice show impaired learning of the water-maze task and deficits in measures of working memory on the radial maze due to behavioral perseverance and stereotypy. They exhibit a hyperreactivity toward a novel object but normal anxiety-like behavior. The behavioral changes are associated with abnormalities of the mossy fiber projection and an up-regulation of GR expression in the hippocampus. Adult mutant mice show normal corticosterone levels at circadian trough and peak. This genetic model provides important information about the consequences of a permanently altered balance between limbic MR and GR, with implications for stress-related neuroendocrine and neuropsychiatric diseases.

Animals↗
PubMed1998

Sustained long term potentiation and anxiety in mice lacking the Mas protooncogene.

The Mas protooncogene is a maternally imprinted gene encoding an orphan G protein-coupled receptor expressed mainly in forebrain and testis. Here, we provide evidence for a function of Mas in the central nervous system. Targeted disruption of the Mas protooncogene leads to an increased durability of long term potentiation in the dentate gyrus, without affecting hippocampal morphology, basal synaptic transmission, and presynaptic function. In addition, Mas-/- mice show alterations in the onset of depotentiation. The permissive influence of Mas ablation on hippocampal synaptic plasticity is paralleled by behavioral changes. While spatial learning in the Morris water maze is not significantly influenced, Mas-deficient animals display an increased anxiety as assessed in the elevated-plus maze. Thus, Mas is an important modulating factor in the electrophysiology of the hippocampus and is involved in behavioral pathways in the adult brain.

Animals↗
PubMedDate not supplied

Transgenic mice expressing a truncated form of CREB-binding protein (CBP) exhibit deficits in hippocampal synaptic plasticity and memory storage.

Deletions, translocations, or point mutations in the CREB-binding protein (CBP) gene have been associated with Rubinstein-Taybi Syndrome; a human developmental disorder characterized by retarded growth and reduced mental function. To examine the role of CBP in memory, transgenic mice were generated in which the CaMKII alpha promoter drives expression of an inhibitory truncated CBP protein in forebrain neurons. Examination of hippocampal long-term potentiation (LTP), a form of synaptic plasticity thought to underlie memory storage, revealed significantly reduced late-phase LTP induced by dopamine-regulated potentiation in hippocampal slices from CBP transgenic mice. However, four-train induced late-phase LTP is normal. Behaviorally, CBP transgenic mice exhibited memory deficits in spatial learning in the Morris water maze and deficits in long-term memory for contextual fear conditioning, two hippocampus-dependent tasks. Together, these results demonstrate that CBP is involved in specific forms of hippocampal synaptic plasticity and hippocampus-dependent long-term memory formation.

Animals↗
PubMed2005

Antihypertensive and cognitive effects of grape polyphenols in estrogen-depleted, female, spontaneously hypertensive rats.

Both endogenous and dietary estrogens reduce hypertension and enhance cognitive abilities in estrogen-depleted female spontaneously hypertensive rats (SHR). Many of the beneficial effects of estrogens/phytoestrogens also appear to be provided by other polyphenols (e.g., proanthocyanidins) in grape seed, which lack appreciable estrogenic receptor binding. The present study tested the hypothesis that similar to phytoestrogens, proanthrocyanidins in grape seed polyphenols reduce salt-sensitive hypertension in young, estrogen-depleted SHR. SHR were ovariectomized at 4 wk of age and placed on phytoestrogen-free diets with or without 0.5% grape seed extract added and with high (8.0%) or basal (0.6%) NaCl. After 10 wk on the diets, grape proanthrocyanidin supplementation significantly reduced arterial pressure in the rats fed the basal (10 mmHg) and high (26 mmHg)-NaCl diet, compared with the nonsupplemented controls. In vitro superoxide production was significantly reduced (23%) by the grape seed polyphenols. Spatial learning (8-arm-radial maze) in the SHR on the basal NaCl diets was improved by dietary grape seed polyphenols. These results indicate that grape seed polyphenols decrease arterial pressure in SHR, probably via an antioxidant mechanism.

Animals↗
PubMed1999

[Effect of prenatal stress on learning of rats in the Morris test].

Prenatal stress was found not to affect learning capability in Morris Water Maze in rats, although some difference was revealed in the rats behaviour. 2-month old rats who had been subjected to a prenatal stress, revealed an obvious trend towards less flexible strategy of behaviour and perseveration. At the age of 4 months, the difference between the control and experimental groups becomes negligible.

Animals↗
PubMed2005

NIH Swiss and Black Swiss mice have retinal degeneration and performance deficits in cognitive tests.

Swiss mice are among the most commonly used outbred strains in biomedical research. Because prior knowledge of the baseline phenotypes of mouse strains will allow informed selection of strains for particular experiments, we sought to characterize the behavior of two previously untested outbred Swiss strains--NIH Swiss and Black Swiss--in the two most widely used paradigms for evaluating the cognitive abilities of mice. Unlike the C57BL/6J and C57BL/6J-Tyr(c-2J) controls, animals of both outbred Swiss strains were unable to demonstrate learning in the Morris water maze and contextual fear conditioning paradigms. A polymerase chain reaction assay revealed that all of the NIH Swiss and Black Swiss mice tested were homozygous for the recessive retinal degeneration 1 mutation of the Pde6b gene. Histological examination of NIH Swiss and Black Swiss mouse eyes confirmed the presence of retinal degeneration, which causes visual image blindness. These findings indicate that NIH Swiss and Black Swiss mice are visually im paired and thus may be unsuitable for use in some experiments.

Animals↗
PubMed1998

Intracerebroventricular injection of N omega-nitro-L-arginine in rats impairs learning in a 14-unit T-maze.

We investigated whether intracerebroventricular (i.c.v.) infusion of the nitric oxide synthase inhibitor, Nomega-nitro-L-arginine (N-Arg), impairs learning in male Sprague-Dawley rats (2-3 months old) in a 14-unit T-maze. Rats were pretrained in one-way active avoidance to a criterion of 13/15 avoidances of foot shock in a straight runway. The next day, rats received i.c.v. injections of either artificial cerebrospinal fluid (aCSF) as controls or N-Arg (12 microg or 15 microg) 30 min before training in the 14-unit T-maze. The learning contingency was to negotiate each of 5 segments within 10 s to avoid footshock during 15 trials. Performance variables included errors (deviations from the correct pathway), runtime from start to goal, and shock frequency and duration. Compared to controls, the number of errors over the last 10 trials was higher in rats receiving 15 microg N-Arg and over the last 5 trials for those given 12 microg. Runtime, shock frequency and duration were increased in both N-Arg groups. The N-Arg-induced (15 microg i.c.v.) impairment could be attenuated when the nitric oxide donor, sodium nitroprusside (1 mg/kg), was administered intraperitoneally 1 min prior to maze learning. In a retention test, rats were treated with either aCSF or 15 microg N-Arg i.c.v. 30 min before being retested in the maze 7-10 d following acquisition training. Under these conditions, maze performance was not significantly affected. These results confirmed previous findings that inhibition of nitric oxide synthase impairs acquisition but not retention. Moreover, the N-Arg-induced learning impairment does not appear to be related to noncognitive aspects of performance.

Analysis of Variance↗
PubMed2003

Role of the neocortex in the water maze task in the rat: a detailed behavioral and Golgi-Cox analysis.

The role of the neocortex in acquisition of the water maze task was investigated with both detailed behavioral and anatomical analyses. The neocortical areas examined were: (1). primary visual and posterior parietal areas Oc1 and Oc2M, (2). parietal area Par1, and (3). prefrontal areas Cg1, Cg3, IL, and part of Fr2 of Zilles, 1985. In Experiment 1, the effects of lesions in these areas were examined separately in different groups of naive male hooded rats. Additional rats were given water maze strategy pretraining before receiving a lesion. Strategy pretraining was used to separate water maze strategy learning from spatial learning to evaluate the contribution of the neocortical areas to these two components of task acquisition. All groups of naive lesioned rats were impaired in the task. In contrast, corresponding groups of pretrained lesioned rats performed as well as controls on all behavioral measures. In Experiment 2, the same neocortical areas lesioned in Experiment 1 were examined with the Golgi-Cox method to determine whether water maze training was associated with changes in the dendritic arborization of neocortical pyramidal cells. Contrary to expectations, no anatomical changes that could be ascribed to the behavioral training were seen in the areas and cortical layers examined. The data suggest that (1). these areas contribute to water maze strategy learning in naive rats, (2). none of the areas are crucially required for spatial learning provided rats are familiar with the general behavioral strategies required in the task before the lesion is made, and (3). any changes in neuronal morphology that occur as a consequence of the training may be subtle and widely distributed.

Animals↗
PubMedDate not supplied

[Comparative study of the effect of picamilone and piracetam on learning in rats in a radial maze].

During four weeks rats were learned to visit consequently 4 baited arms in the 8-armed radial maze. Picamilone (nicotinoyl-GABA) in a dose of 10 mg/kg daily accelerated rats to reach 80% level of learning (to 20-28 trials). After picamilone injections rats obtained the maximal level of short-term memory as just 3-5 trials. Piracetam in a dose of 200 mg/kg daily exerted no effects on long-term and short-term memory of rats in the radial maze.

Animals↗