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PubMed2006

Effects of uridine in models of epileptogenesis and seizures.

Due to the limited efficacy and side effects of current antiepileptic drugs (AEDs), the search for new therapeutic agents is critical. Uridine, a possible endogenous antiepileptic modulator, has been demonstrated to have anticonvulsant effects in some models of epilepsy, but not others. In this study, we examined possible neuroprotective effects of uridine by administering the agent following lithium-pilocarpine induced status epilepticus. The effects of uridine were assessed on EEG patterns, visual-spatial memory in the water maze and histopathology. There was a trend for reduced EEG spike frequency, improved visual spatial memory and better histology score in rats receiving uridine. The antiepileptogenic and anticonvulsant effects of uridine were studied by administering uridine to rats undergoing rapid kindling or following full kindling. In the rapid kindling models, uridine had a moderate antiepileptogenic and anticonvulsant effect. These results suggest uridine may have potential to aid in the prevention and treatment of epilepsy.

Animals↗
PubMed2006

The effects of the anti-cancer drugs, methotrexate and 5-fluorouracil, on cognitive function in mice.

There is evidence that standard-dose chemotherapy may impact cognitive function in cancer patients. The present study evaluated the effects of a combination of two anti-cancer drugs, methotrexate (37.5 mg/kg) and 5-fluorouracil (5FU, 75 mg/kg) on cognitive function in a mouse model. Drug-induced deficits were observed in adult BALB/C mice on tests of spatial memory, non-matching-to-sample (NMTS) learning and in a delayed-NMTS test of non-spatial memory. There were no group differences on tests of cued memory or discrimination learning. Performance-related variables were ruled out as possible explanations of the observed impairments. The impaired performance of the drug group, which was consistent with cognitive deficits observed in human cancer patients treated with similar types of chemotherapy, was attributed to functional changes in specific brain regions, including the frontal lobes and hippocampus.

Animals↗
PubMed2000

Racial effects on neuropsychological functioning in schizophrenia.

OBJECTIVE: This study assessed the effects of race on neuropsychological functioning in patients with schizophrenia. METHOD: A total of 160 patients with schizophrenia completed an extensive neuropsychological test battery. Scores were standardized to a group of 99 psychiatrically and physically healthy subjects and categorized into seven functional domains: concentration, executive function, language, motor function, spatial memory, verbal memory, and visual processing. RESULTS: African Americans (N=25) had significantly lower mean scores on executive function, language, spatial memory, and visual processing than did Caucasians (N=135). Statistical control for patient and family education eliminated all significant effects. CONCLUSIONS: Educational differences in patients and families may account for some of the performance heterogeneity reported in patients with schizophrenia and should be routinely analyzed with other sociodemographic factors such as race and sex.

Black People↗
PubMed2005

The role of working memory in spatial enumeration: patterns of selective interference in subitizing and counting.

Articulatory suppression (repeatedly pronouncing a syllable or word while carrying out another task) is thought to interfere selectively with the phonological store in working memory. Although suppression interferes with temporal enumeration (enumerating successive light flashes), to date there has been little evidence of such interference in spatial enumeration (enumerating units laid out in space at one time)--a finding with serious ramifications for theories of enumeration. Participants carried out a spatial enumeration task, enumerating 1-8 dots while listening to a metronome (baseline condition) or while carrying out a secondary task to the rhythm of the metronome (dual-task condition). There were four secondary tasks: simple articulation (saying a letter), complex articulation (alternating between two letters), simple tapping (tapping a finger), and complex tapping (alternating between two fingers). Interference varied with number of items, but the pattern differed from that observed with temporal enumeration.

Association Learning↗
PubMedDate not supplied

Modulation of hippocampal plasticity and cognitive behavior by short-term blueberry supplementation in aged rats.

During aging, reductions in hippocampal neurogenesis are associated with memory decline indicating a causal relationship. Indeed, insulin-like growth factor-1 (IGF-1), a major activator of the extracellular receptor kinase pathway that is central in learning and memory processes, is also a key modulator of hippocampal neurogenesis. Previously, we showed that age-related declines in spatial memory tasks can be improved by antioxidant-rich diets containing blueberries. In this study, to begin to understand the mechanisms responsible for the beneficial effects of blueberries, we assessed changes in hippocampal plasticity parameters such as hippocampal neurogenesis, extracellular receptor kinase activation, and IGF-1 and IGF-1R levels in blueberry-supplemented aged animals. Our results show that all these parameters of hippocampal neuronal plasticity are increased in supplemented animals and aspects such as proliferation, extracellular receptor kinase activation and IGF-1 and IGF-1R levels correlate with improvements in spatial memory. Therefore, cognitive improvements afforded by polyphenolic-rich fruits such as blueberries appear, in part, to be mediated by their effects on hippocampal plasticity.

Aging↗
PubMed1998

Reversal of ischemic-induced chronic memory dysfunction in aging rats with a free radical scavenger-glycolytic intermediate combination.

Rats were subjected to bilateral carotid artery occlusion (2-VO) or sham occlusion (No-VO) and tested 12 weeks for visuo-spatial memory (VSM) function. After 14 weeks, 2-VO rats (N = 4) showing severe visuo-spatial memory impairment were given dimethyl sulfoxide (DMSO)-fructose 1,6-diphosphate (FDP) i.p. for seven days and retested on the water maze. After DMSO-FDP, a 54% improvement in their VSM was seen which nearly reached control No-VO values. Untreated 2-VO (N = 4) and No-VO (N = 8) rats showed no significant changes in their VSM. DMSO-FDP treatment was discontinued and rats were retested on the water maze but improvement was lost and VSM function regressed to pretreatment levels. Immunohistochemical examination showed minimal neuronal damage in all 2-VO rats and slight loss of microtubule associated protein-2. Glial fibrillary acidic protein immunostaining increase was observed only in untreated 2-VO rats. The results indicate that a DMSO-FDP combination improves VSM secondary to chronic brain hypoperfusion.

Aging↗
PubMedDate not supplied

Landmark discrimination learning in the dog.

Allocentric spatial memory was studied in dogs of varying ages and sources using a landmark discrimination task. The primary goal of this study was to develop a protocol to test landmark discrimination learning in the dog. Using a modified version of a landmark test developed for use in monkeys, we successfully trained dogs to make a spatial discrimination on the basis of the position of a visual landmark relative to two identical discriminanda. Task performance decreased, however, as the distance between the landmark and the "discriminandum" was increased. A subgroup of these dogs was also tested on a delayed nonmatching to position spatial memory task (DNMP), which relies on egocentric spatial cues. These findings suggest that dogs can acquire both allocentric and egocentric spatial tasks. These data provide a useful tool for evaluating the ability of canines to use allocentric cues in spatial learning.

Animals↗
PubMed2003

Brain-derived neurotrophic factor/TrkB signaling in memory processes.

Activity-dependent changes in synaptic strength are considered mechanisms underlying learning and memory. Brain-derived neurotrophic factor (BDNF) plays an important role in activity-dependent synaptic plasticity such as long-term potentiation. Recent experimental evidence supports the role of BDNF in memory processes: Memory acquisition and consolidation are associated with an increase in BDNF mRNA expression and the activation of its receptor TrkB. Genetic as well as pharmacologic deprivation of BDNF or TrkB impairs learning and memory. In a positively motivated radial arm maze test, activation of the TrkB/phosphatidylinositol-3 kinase (PI3-K) signaling pathway in the hippocampus is associated with consolidation of spatial memory through an activation of translational processes. In a negatively motivated passive avoidance test, mitogen-activated protein kinase (MAPK) is activated during acquisition of fear memory. Furthermore, recent findings suggest the importance of interaction between BDNF/TrkB signaling and NMDA receptors for spatial memory. A Src-family tyrosine kinase, Fyn plays a role in this interaction by linking TrkB with NR2B. These findings suggest that BDNF/TrkB signaling in the hippocampus plays a crucial role in learning and memory.

Animals↗
PubMed2006

A role in learning for SRF: deletion in the adult forebrain disrupts LTD and the formation of an immediate memory of a novel context.

Whereas significant insight exists as to how LTP-related changes can contribute to the formation of long-term memory, little is known about the role of hippocampal LTD-like changes in learning and memory storage. We describe a mouse lacking the transcription factor SRF in the adult forebrain. This mouse could not acquire a hippocampus-based immediate memory for a novel context even across a few minute timespan, which led to a profound but selective deficit in explicit spatial memory. These animals were also impaired in the induction of LTD, including LTD triggered by a cholinergic agonist. Moreover, genes regulating two processes essential for LTD-calcium release from intracellular stores and phosphatase activation-were abnormally expressed in knockouts. These findings suggest that for the hippocampus to form associative spatial memories through LTP-like processes, it must first undergo learning of the context per se through exploration and the learning of familiarity, which requires LTD-like processes.

Animals↗
PubMed2003

Morphological alterations in the occipital cortex of aged rats with impaired memory: a Golgi-Cox study.

This study investigated a possible link between morphological alterations of pyramidal neurons in layer V of the occipital cortex and the degree of spatial memory impairment in aged rats. Measurements of cortical thickness, density of dendritic branching, and spine counts were carried out in young adult (5 months old) and aged (26 months old) Long-Evans female rats on Golgi-Cox silver-stained material. Using the water-maze task, well- and poorly performing rats were distinguished statistically on the basis of their reference-memory scores. When subsequently compared with young rats or to aged rats with good performances, the well-performing rats had a reduced cortical thickness and exhibited weaker high-order branching of basal dendrites on their pyramidal neurons. When dendritic spines were counted on a 50-microm-long straight portion of a basal dendrite, no difference was observed between young and aged rats. Our results suggest that structural alterations affecting pyramidal neurons in the occipital cortex of aged rats may contribute to spatial memory impairment. Indeed, in a subpopulation of well-performing aged rats, these structural alterations were less marked than in the population of bad performers.

Aging↗
PubMed1992

Effects of tetrahydroaminoacridine on spatial navigation of nucleus-basalis- and frontal-cortex-lesioned rats.

The present study investigates the effects of tetrahydroaminoacridine (THA: 1 and 3 mg/kg) on water maze (WM) spatial learning performance of intact, nucleus-basalis- (NB) lesioned, frontal-cortex- (FR) lesioned, or NB + FR-lesioned rats. NB lesions did not impair WM learning and had no effect on the WM performance deficit in FR-lesioned rats. THA at 1 or 3 mg/kg did not improve WM spatial memory of intact, NB-, FR-, or NB + FR-lesioned rats. These results suggest that 1) the cholinergic NB system is not a prerequisite for frontally mediated acquisition of WM performance, 2) THA treatment does not enhance spatial memory, and 3) THA is not effective in alleviating cognitive deficits induced by degeneration of the frontal cortex.

Animals↗
PubMed2003

Locomotion, incidental learning, and the selection of spatial reference systems.

In three experiments, we examined the effects of locomotion and incidental learning on the formation of spatial memories. Participants learned the locations of objects in a room and then made judgments of relative direction, using their memories (e.g., "Imagine you are standing at the clock, facing the jar. Point to the book"). The experiments manipulated the number of headings experienced, the amount of interaction with the objects, and whether the participants were informed that their memories of the layout would be tested. When participants were required to maintain a constant body orientation during learning (Experiment 1), they represented the layout in terms of a single reference direction parallel to that orientation. When they were allowed to move freely in the room (Experiment 2), they seemed to use two orthogonal reference axes aligned with the walls of the enclosing room. Extensive movement under incidental learning conditions (Experiment 3) yielded a mixture of these two encoding strategies across participants. There was no evidence that locomotion, interaction with objects, or incidental learning led to the formation of spatial memories that differed from those formed from static viewing.

Adult↗
PubMed1978

Effect of familiarity on primacy performance of normal and retarded children.

On the assumption that serial recall tasks reflect spatial memory rather than verbal rehearsal, the purpose of this experiment was to determine what effect stimulus familiarity had on the spatial primacy performance of 20 retarded and 20 normal boys and girls. Linear presentation effects of familiar and nonfamiliar pictures upon serial position curve performance when overt verbalization was suppressed were investigated. Results indicated that an interaction of stimulus familiarity and spatial memory is responsible for the primacy effect found in serial position curves. No primacy effect for either the normal or retardate group was found in the nonfamiliar stimulus condition. No overall developmental effects were found between groups of children on serial position performance. Consistent with Craik and Lockhart's memory processing model, the present results indicated stimulus familiarity provided deeper levels of processing, thereby facilitating primacy effects.

Adolescent↗
PubMed1998

Septal lesions impair the acquisition of a cued place navigation task: attentional or memory deficit?

These experiments were designed to analyze how medial septal lesions reducing the cholinergic innervation in the hippocampus might affect place learning. Rats with quisqualic lesions of the medial septal area (MS) were trained in a water maze and on a homing table where the escape position was located at a spatially fixed position and further indicated by a salient cue suspended above it. The lesioned rats were significantly impaired in reaching the cued escape platform during training. In addition rats, did not show any discrimination of the training sector during a probe trial in which no platform or cue was present. This impairment remained significant during further training in the absence of the cue. When the cued escape platform was located at an unpredictable spatial location, the MS-lesioned rats showed no deficit and spent more time under the cue than control rats during the probe trial. On the homing board, with a salient object in close proximity to the escape hole, the MS rats showed no deficit in escape latencies, although a significant reduction in spatial memory was observed. However, this was overcome by additional training in the absence of the cue. Under these conditions, rats with septal lesions were prone to develop a pure guidance strategy, whereas normal rats combined a guidance strategy with a memory of the escape position relative to more distant landmarks. The presence of a salient cue appeared to decrease attention to environmental landmarks, thus reducing spatial memory. These data confirm the general hypothesis that MS lesions reduce the capacity to rely on a representation of the relation between several landmarks with different salience.

Analysis of Variance↗