Human Memory Function Research Articles

Lipopolysaccharide-induced experimental immune activation does not impair memory functions in humans

Systemic immune activation occurring together with release of peripheral cytokines can affect behavior and the functioning of the central nervous system (CNS). However, it remains unknown whether and to what extent cognitive functions like memory and attention are affected during transient immune activation. We employed a human endotoxemia model and standardized neuropsychological tests to assess the cognitive effects of an experimental inflammation in two groups of 12 healthy young men before and after intravenous injection of lipopolysaccharide (LPS, Escherichia coli, 0.4 ng/kg) or physiological saline. Endotoxin administration caused a profound transient physiological response with elevations in body temperature, number of circulating neutrophils, and increases in plasma cytokine levels [interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α], and concentrations of norepinephrine, ACTH and cortisol. However, these changes in immune and neuroendocrine parameters were not associated with alterations of memory performance, selective attention or executive functions.

The butanol fraction of Eclipta prostrata (Linn) increases the formation of brain acetylcholine and decreases oxidative stress in the brain and serum of cesarean-derived rats

Eclipta prostrata has been used as a traditional medicinal plant to prevent dementia and to enhance memory in Asia. Its potential as a nootropic and as an antioxidant have been reported in mice. We hypothesized that Eclipta may affect the formation of neurotransmitters and the inhibition of oxidative stress. Charles River cesarean-derived rats (male, 180 ± 10 g) were fed experimental diets supplemented with 0 mg (control), 25 mg (E25), 50 mg (E50), or 100 mg (E100) of a freeze-dried butanol fraction of E prostrata per kilogram of diet for 6 weeks. The acetylcholine level was significantly increased by 9.6% and 12.1% in the brains of E50 and E100 groups, respectively, as compared with the control group that was fed standard diet alone. The acetylcholine esterase activity was significantly increased by 13.1% and 19.7% in the brains of E50 and E100 groups, respectively, compared with the control group. Monoamine oxidase-B activity was significantly decreased by 10.5% in the brains of the E100 group, and the superoxide radical level was significantly reduced by 9.4% in the serum of the E100 group compared with the control group. Superoxide dismutase activity was significantly increased by 9.6% and 11.6% in the serum of E50 and E100 groups, respectively, compared with the control group. These results clearly demonstrate the effects of E prostrata on the formation of acetylcholine in the brain and the inhibition of oxidative stress in the brain and serum of rats. These findings may have implications for preventing dementia and enhancing memory function in humans.

Designing and implementing a Role-Playing Game: A tool to explain factors, decision making and landscape transformation

In this paper we describe a research process on contextual driving factors and decision-making processes used by local actors for land use change in a zone of the Colombian Amazonian frontier. We integrated landscape multi-temporal analysis, Role-Playing Games (RPG), interviews based on flow diagrams and an historical study of landscape dynamics for the construction of our methodological approach. Findings of the study include individual detailed decision-making insights at the farm level that shed light on the mechanisms that boost the advance of the agricultural frontier into the Amazonian forest. We illustrate how individual decisions are related with the general landscape dynamics. A formalization of results was carried out in UML (Unified Modeling Language) for the future construction of a Multi Agent System (MAS) model, the implementation of which will be useful for land use planning, discussions among local and regional actors and scenario building. The RPG constitutes a device that could “talk” by itself, in the name of local actors. Facts that hardly would be communicated in an interview emerge implicitly and explicitly through the exercise. The RPG is a device that we call a “dense methodological tool”, in the sense that it is a designed object that synthesizes a complex system. This is central to territorial planning because RPG and derived MAS models talk to actors and researchers in the same language that human memory and projection mental capabilities function. These objects condense time and space and help make problems clear, and they assist in the finding of solutions and exploration of possible scenarios.

Variants in doublecortin- and calmodulin kinase like 1, a gene up-regulated by BDNF, are associated with memory and general cognitive abilities.

BackgroundHuman memory and general cognitive abilities are complex functions of high heritability and wide variability in the population. The brain-derived neurotrophic factor (BDNF) plays an important role in mammalian memory formation.Methodology / Principal FindingBased on the identification of genes markedly up-regulated during BDNF-induced synaptic consolidation in the hippocampus, we selected genetic variants that were tested in three independent samples, from Norway and Scotland, of adult individuals examined for cognitive abilities. In all samples, we show that markers in the doublecortin- and calmodulin kinase like 1 (DCLK1) gene, are significantly associated with general cognition (IQ scores) and verbal memory function, resisting multiple testing. DCLK1 is a complex gene with multiple transcripts which vary in expression and function. We show that the short variants are all up-regulated after BDNF treatment in the rat hippocampus, and that they are expressed in the adult human brain (mostly in cortices and hippocampus). We demonstrate that several of the associated variants are located in potential alternative promoter- and cis-regulatory elements of the gene and that they affect BDNF-mediated expression of short DCLK1 transcripts in a reporter system.ConclusionThese data present DCLK1 as a functionally pertinent gene involved in human memory and cognitive functions.

A model of episodic memory: Mental time travel along encoded trajectories using grid cells

The definition of episodic memory includes the concept of mental time travel: the ability to re-experience a previously experienced trajectory through continuous dimensions of space and time, and to recall specific events or stimuli along this trajectory. Lesions of the hippocampus and entorhinal cortex impair human episodic memory function and impair rat performance in tasks that could be solved by retrieval of trajectories. Recent physiological data suggests a novel model for encoding and retrieval of trajectories, and for associating specific stimuli with specific positions along the trajectory. During encoding in the model, external input drives the activity of head direction cells. Entorhinal grid cells integrate the head direction input to update an internal representation of location, and drive hippocampal place cells. Trajectories are encoded by Hebbian modification of excitatory synaptic connections between hippocampal place cells and head direction cells driven by external action. Associations are also formed between hippocampal cells and sensory stimuli. During retrieval, a sensory input cue activates hippocampal cells that drive head direction activity via previously modified synapses. Persistent spiking of head direction cells maintains the direction and speed of the action, updating the activity of entorhinal grid cells that thereby further update place cell activity. Additional cells, termed arc length cells, provide coding of trajectory segments based on the one-dimensional arc length from the context of prior actions or states, overcoming ambiguity where the overlap of trajectory segments causes multiple head directions to be associated with one place. These mechanisms allow retrieval of complex, self-crossing trajectories as continuous curves through space and time.

Further support for a role of the His452Tyr variant in 5-HT2A receptor gene in memory functions in humans

Wagner et al. (2008) recently published a brief report in the International Journal of Neuropsychopharmacology , which replicated the previous findings of de Quervain et al. (2003) and indicated that the functional 5-HT2A receptor variant, His452Tyr (rs6314), is associated with episodic long-term memory in humans. There is considerable evidence from studies in animals and humans that serotonin is pivotally implicated in learning and memory (e.g. Buhot, 1997). The tyrosine (Tyr) allele of the His452Tyr variant in the human 5-HT2A receptor is associated with blunted receptor response upon serotonin stimulation (Ozaki et al. 1997) with effects on intracellular calcium levels and protein kinase-A phosphorylation, both of which are important for memory formation at the cellular level. This would influence performance on memory tasks, as has been shown for pharmacological manipulation of serotonin receptors (Meneses, 2007). Wagner et al. (2008) compared 113 His/His carriers to 20 His/Tyr carriers on a variety of cognitive tests. They hypothesized that the His/Tyr group would manifest poorer performance on long-term recall and recognition tasks. To test the discriminant validity of the variant (i.e. that the variant is specifically related to long-term episodic memory functions and not to other cognitive functions), Wagner et al. (2008) also tested performance differences between the groups on tasks measuring short-term memory, attention and executive functions. The results showed that the His/Tyr group recognized and recalled fewer words than the His/His group on an auditory, free recall, learning task with a 30-min retention interval between learning phase and test phase. There was no similar pattern of difference for tasks measuring attention and executive functioning. We obtained further data on the association between the 5-HT2A receptor His452Tyr variant and memory function from the ‘Why Do Young Women Smoke?’ (WDYWS) project, a study ongoing …

Effects of the stress of marathon running on implicit and explicit memory

We tested the idea that real-world situations, such as the highly strenuous exercise involved in marathon running, that impose extreme physical demands on an individual may result in neurohormonal changes that alter the functioning of memory. Marathon runners were given implicit and explicit memory tasks before or immediately after they completed a marathon. Runners tested immediately upon completing the marathon showed impairment in the explicit memory task but enhancement in the implicit memory task. This postmarathon impairment in explicit memory is similar to that seen with amnesic patients with organic brain damage. However, no previous studies have shown a simultaneous enhancement in the implicit memory task, as shown by the marathon runners in the present study. This study indicates that human memory functioning can be dynamically altered by such activities as marathon running, in which hundreds of thousands of healthy normal individuals routinely partake.

The levo enantiomer of amphetamine increases memory consolidation and gene expression in the hippocampus without producing locomotor stimulation

Dextro-amphetamine enhances memory and other cognitive functions in animals and humans. The use of d-amphetamine as a memory enhancer, however, is limited by a robust stimulatory side-effect profile caused by release of dopamine. The levo enantiomer of amphetamine has been shown to be considerably less effective as a dopamine releaser and less potent in producing the stimulatory effects characteristic of d-amphetamine. In order to determine whether l-amphetamine and the structurally related compound, l-methamphetamine, retain cognitive-enhancing effects despite their lack of stimulatory activity, we administered the compounds to rats prior to activity monitoring experiments, and in different animals, immediately after training on inhibitory avoidance and object recognition tasks. Results demonstrated that l-amphetamine and l-methamphetamine did not increase locomotion and stereotypies beyond control levels, but did produce significant memory enhancement. In addition, l-amphetamine and l-methamphetamine alleviated scopolamine-induced amnesia in the inhibitory avoidance task. In all cases, these compounds produced an effect comparable to that of d-amphetamine, but required only one quarter of the d-amphetamine dose to produce the same effect size. We also found that l-amphetamine modulates learning-induced changes in hippocampal Arc/Arg3.1 protein synthesis that correlate with memory consolidation. These results suggest that l-amphetamine and l-methamphetamine are potent memory enhancers in rats and may ultimately be useful for treating memory disorders in humans.

P03-217 Kibra allelic variation is associated with memory processes in early onset schizophrenia

Background:A single nucleotide polymorphism, rs17070145, in the KIBRA protein, is thought to influence memory function in humans (Papassotiropoulos et al, 2006). We sought to investigate its effect on memory performance in people with Early Onset Schizophrenia (EOS; onset before age of 18) and their first-degree relatives.Methods:53 EOS probands and 117 non-psychotic first-degree relatives were examined on IQ (Wechsler Adult Intelligence Scale-Revised), learning and memory (California Verbal Learning Test; CVLT). the Structured Clinical Interview for DSM-IV yielded four diagnostic groups: EOS probands; relatives with Mood Disorders; other Axis I diagnoses; and no diagnosis (healthy relatives). Analysis of co-variance was performed, with diagnosis and genotype as fixed factors and age as covariate.Results:Carriers of the rs17070145 T allele achieved higher performance IQ, and recalled more words in short-delayed and long-delayed recall in the CVLT compared to C allele carriers [p< 0.003 and p< 0.009, respectively]. However TT homozygotes made more perseverative errors than C allele carriers [p=0.04]. after applying the Bonferroni for multiple comparisons, a genotype by diagnosis interaction revealed that relatives who were TT homozygotes and had mood disorders performed better on long-delayed recall [p< 0.04] but made more intrusion errors in the CVLT than the CC/CT genotype group.Conclusions:KIBRA may be involved in:1.processes that enhance overall competence in non-verbal tasks;2.phenotypic expression of cognition in mentally unwell relatives of schizophrenia patients.

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is not significantly correlated to Transient Global Amnesia: Preliminary results of an on-going study in Brescia Province, Italy

Transient Global Amnesia (TGA) is a well defined pure amnesic clinical syndrome characterized by acute loss of memory in middle aged people. The aetiology of TGA is still unknown but clinical and neuroimaging studies support a hippocampi involvement, and some reports suggested a possible common genetic background in cases of familial TGA. A single nucleotide polymorphism (SNP) in the Brain-derived neurotrophic factor (BDNF) gene that causes a valine to methionine substitution at codon 66 (Val66Met) has been demonstrated to affect human memory and hippocampal function in the development and maintenance of adult neurons. Aim of this study was to evaluate the role of BDNF Val66Met polymorphism on TGA risk and all TGA clinical features. Ninety-eight TGA patients and 93 age-matched controls were enrolled in the study. Each patient underwent clinical and neurological examination, routine blood examination, EEG, Jugular vein valve (JVI) competence assessment, and neuroimaging study. TGA characteristics were carefully recorded. The distribution of BDNF genotype did not differ in TGA patients compared to controls (BDNF GG: 58.2% vs 55.9%, GA: 33.7% vs 36.6%, AA: 8.1% vs 7.5%, P=.91) as well as allele frequency (BDNF G, TGA vs CON: 75.0% vs 74.2, P=.47). No significant differences in age at onset, disease duration and recurrence or the presence of predisposing factors between TGA patients carrying BDNF AA, BDNF GA and BDNF GG genotype were found. This study, that firstly looked at genetic background in TGA, did not show a significant correlation between the BDNF Val66Met polymorphism and age of onset, risk factors, duration or recurrence of TGA.

Noninvasive brain stimulation with transcranial magnetic or direct current stimulation (TMS/tDCS)—From insights into human memory to therapy of its dysfunction

Noninvasive stimulation of the brain by means of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) has driven important discoveries in the field of human memory functions. Stand-alone or in combination with other brain mapping techniques noninvasive brain stimulation can assess issues such as location and timing of brain activity, connectivity and plasticity of neural circuits and functional relevance of a circumscribed brain area to a given cognitive task. In this emerging field, major advances in technology have been made in a relatively short period. New stimulation protocols and, especially, the progress in the application of tDCS have made it possible to obtain longer and much clearer inhibitory or facilitatory effects even after the stimulation has ceased. In this introductory review, we outline the basic principles, discuss technical limitations and describe how noninvasive brain stimulation can be used to study human memory functions in vivo. Though improvement of cognitive functions through noninvasive brain stimulation is promising, it still remains an exciting challenge to extend the use of TMS and tDCS from research tools in neuroscience to the treatment of neurological and psychiatric patients.

The effect of a REM sleep deprivation procedure on different aspects of memory function in humans

Previous studies have suggested that memory is dependent on the occurrence of REM sleep. Research has mainly focused on two distinct types of memory function, declarative and procedural, and it seems that the latter may more directly depend on REM sleep. Memory consolidation has been more investigated than acquisition, maintenance, and recall, despite the fact that sleep may affect flow of information into/from storage. Moreover, tests have often been limited to stimuli within only one modality (usually visual or verbal). This study aimed to clarify the role of REM sleep in memory by investigating aspects of memory function, processing, and modality in the same experimental setting. Tests of acquisition and consolidation of multiple aspects of memory function within the visual and verbal modalities were administrated to subjects before and after REM sleep deprivation. Results show that test performance was not affected by REM sleep deprivation.

Getting from neuron to checkmark: models and methods in cognitive survey research

AbstractSince the 1980s much work has been done in the field of Cognitive Survey Research. In an interdisciplinary endeavour, survey methodologists and cognitive psychologists (as well as social psychologists and linguists) have worked to unravel the cognitive processes underlying survey responses: to improve survey measurement, but also to obtain fundamental insight into the process of question answering, the nature of attitudes, the functioning of human memory, etc. Yet, despite the amount of work that has been done, less progress has been made than was deemed possible. This paper suggests ways in which to develop cognitive theories that may help to obtain an integrated understanding of question answering in surveys. One way to build better theories is to focus on model construction. Different types of cognitive models are discussed that can be used to model question answering. Second, a larger variety of methods from the cognitive toolbox can be used to further develop and test these models. An overview is given of the various tools available to researchers of cognitive aspects of survey research, with a special focus on newer methods from cognitive neuroscience. To connect different tools and methods into an integrative theory of question answering, the idea of hierarchical modelling is proposed. Copyright © 2007 John Wiley & Sons, Ltd.

No association between the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and schizophrenia in Asian populations: Evidence from a case–control study and meta-analysis

Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that plays an important role in the development and maintenance of adult neurons and is important regulator of synaptic plasticity in human brain. It has been reported that there are alterations in BDNF levels in the brains of patients with schizophrenia. It has also been reported that transneuronal transfer of BDNF is dependent on neuronal activity, suggesting that BDNF plays an important role in neurotransmission. A single nucleotide polymorphism (SNP) in the BDNF gene that causes a valine to methionine substitution at codon 66 (Val66Met) has been demonstrated to affect human memory and hippocampal function. A possible positive association between the BDNF Val66Met polymorphism and schizophrenia has also been shown in Scottish and Spanish populations. Furthermore, the BDNF Val66Met polymorphism has been implicated in the age of onset of schizophrenia. In the present study, we attempted to replicate these findings in a Japanese case–control sample (211 patients with schizophrenia and 205 controls). We did not find an association between the BDNF Val66Met polymorphism and schizophrenia. An association between the Val66Met polymorphism and age of onset was not observed either. Furthermore, a meta-analysis including the present and previous Asian studies comparing 2059 patients with schizophrenia and 2765 controls also revealed no significant association between the BDNF Val66Met polymorphism and schizophrenia. Our results do not support a significant role for the BDNF Val66Met polymorphism in the development of schizophrenia in Asian populations.

Effects of intranasal insulin on cognitive function and body composition

Systemic insulin has rapid access to the brain by a receptor-mediated transport system located in endothelial cells of brain microvessels. In several species, including man, parallel increases in the concentration of insulin in the cerebrospinal fluid (CSF) after acute elevation of plasma insulin levels are well documented. In animal studies central nervous insulin has been shown to play an important role in body weight regulation and memory function. Direct intracerebroventricular administration of insulin reduced food intake and caused weight loss. Moreover, insulin in the brain has been shown to improve memory function. However, in humans the investigation of central nervous effects of insulin has been hampered by the fact, that infusion of insulin and glucose is not practicable for a longer time to obtain changes in body weight. Recently, we provided evidence, that insulin enters the CSF compartment after intranasal administration without absorption into the blood stream. With this approach, we investigated the effect of long-term intranasal administration on body weight regulation in healthy subjects. After a baseline of 2 weeks 40 lean subjects (16 females, 24 males) were treated for 8 weeks with intranasal insulin (4×40 IU/day) or placebo in a double blind, between subject comparison. Body weight and body composition were measured weekly by bioimpedance analysis. Blood glucose and plasma insulin levels were identical during intranasal administration of insulin and placebo, indicating that no relevant amount of insulin entered the blood stream. There was no decrease in body weight and body fat mass during intranasal insulin administration in woman as compared to placebo. However, in contrast to women, insulin treated men continuously lost body weight compared to the placebo condition (baseline adjusted body weight at the end of the study, placebo: 79.84±0.57kg; insulin: 78.12±0.57kg, p<0.05). Most important, this weight loss was mainly a result of a reduction in body fat mass (placebo: 14.12±0.61kg, insulin: 12.25 0.61g, p<0.05). With the same approach, effects of intranasal administration of insulin (4×40 IU/day) or placebo for 8 weeks on memory function were investigated in 38 healthy subjects (14 females, 24 males). Every week subjects were presented with a word list containing 30 words. One week later they had to tell the words they remembered. Compared to the baseline condition intranasal administration of insulin significantly improved memory function (words recalled, placebo: 2.92±1.00, insulin: 6.20±1.03, p<0.05) at the end of the treatment period. There was no difference in the insulin effects on memory function in males and females. With the same approach, effects of intranasal insulin aspart even exceeded the beneficial effects of human insulin on body fat mass (placebo: +0.45±0.63kg, human insulin: -1.38±0.63kg, insulin aspart: -2.67±0.63kg, p<0.08) and memory function (words recalled, placebo: 1.83±0.75, human insulin: 5.17±1.56, insulin aspart: 8.35±1.09, p<0.05) in 36 healthy men. These results indicate an important role for insulin in body weight regulation and memory function in humans. Concerning recent findings of a reduced transport of insulin across the blood brain barrier in obese subjects and in Alzheimer patients, these findings could be of considerable clinical relevance.

Electrophysiological Measures of Familiarity Memory

Event-related potentials are a valuable tool for the study of human memory function. This selective review provides a brief introduction in models of recognition memory and then describes how ERPs can be used to investigate familiarity memory, an acontextual form of remembering that can be distinguished from the recollection of detailed information of prior events. ERP studies on the mid-frontal old/new effect, the putative electrophysiological correlate of familiarity memory are reviewed. It will be illustrated how familiarity memory is reflected in this effect, how it can electrophysiologically be dissociated from other forms of memory and which brain systems mediate this form of remembering. Recent studies will be reviewed that illustrate that familiarity is not only restricted to single items but can also support the retrieval of associative information.

No evidence for an association between the BDNF Val66Met polymorphism and schizophrenia or personality traits

Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family, which plays a critical role in neurodevelopment. Based on the neurodevelopmental hypothesis, the BDNF gene has been a candidate locus for schizophrenia. In Caucasians, recent studies identified an association with the Val66Met polymorphism, which has been suggested to affect episodic memory and hippocampal function in humans. However, in other populations, the association has not been replicated. In the present study, we investigated the association between the Val66Met polymorphism of the gene and schizophrenia in 401 Japanese patients with schizophrenia and 569 controls. As a result, we did not observe a significant difference in genotypic distribution or allele frequencies between the patients and controls ( χ 2 = 0.56, df = 2, p = 0.76 and χ 2 = 0.39, df = 1, p = 0.53, respectively). We also investigated the association between the polymorphism and personality traits in the controls; however, no significant association was observed. Thus, the present study did not provide evidence for an association between the BDNF gene and schizophrenia or personality traits in the Japanese population.

Sleep-dependent surges in growth hormone do not contribute to sleep-dependent memory consolidation

In the search for the mechanisms that mediate the effects of sleep on the consolidation of memories, growth hormone (GH) recently became of interest, because in humans it is released mainly during slow-wave sleep (SWS), a period of enhanced declarative memory consolidation. In addition, recent studies showed that GH is involved in proper memory function in GH deficient and elderly humans and this effect has been linked to regulatory influences of GH on hippocampal NMDA receptors. Here, we blocked GH secretion by intravenous infusion of somatostatin in healthy young subjects during the first 3 h of sleep, which contain mainly SWS. Declarative and procedural memory consolidation was tested across this period, using a word pair association task and a mirror tracing task, respectively. Although GH was effectively suppressed, memory performance as well as sleep were entirely unaffected by this suppression. Whereas GH may in the long run generally support brain systems required for maintaining proper memory function, our data exclude a necessary contribution of the nocturnal surge in pituitary GH secretion to the acute processing and formation of specific memories during sleep.

The neurofunctional consequences of amphetamine sensitisation on human working memory function – an fMRI investigation

Background Patients with schizophrenia and chronic substance abusers often display deficits in working memory function linked to prefrontal cortical dysfunction. Cortical dopamine transmission strongly influences the efficiency of capacity-constrained prefrontal activity. A recent fMRI study showed that amphetamine modulates cortical processing in line with an inverted-U type dose-response function. Repeated intermittent exposure to amphetamine in primates has been shown to result in augmentation of the behavioural response elicited by the drug (eg: hyperlocomotion) known as sensitisation. Chronic treatment produces cognitive deficits similar to those observed in clinical populations and sensitisation is a well established animal model of behavioural and neurochemical aspects of schizophrenia. In this study we use fMRI to examine the behavioural consequences and neural correlates of working memory function in healthy volunteers displaying behavioural sensitisation.

Cell Proliferation in the Dentate Gyrus of Rat Hippocampus Is Inhibited by Soft Diet Feeding

Background: Recently it has become well accepted that neurogenesis occurs in the dentate gyrus of the hippocampus, a region important to memory and learning function in rodents and humans. Reports show that neurogenesis in the hippocampus is regulated by certain factors, such as exposure to an enriched environment, physical activity, aging and stress. The relationship between the change in the task of chewing as one oral environmental factor, and the mechanisms of hippocampal neuron generation are unclear. Objective: We examined whether cell proliferation varies by chewing tasks with different food textures in the dentate gyrus of the rat hippocampus. Methods: Wistar rats were divided into two groups, one was fed a solid diet, known as the hard-diet feeding group, and the soft-diet feeding group, which was fed a powder diet containing the same components as the solid one for 3, 7, 16 and 24 weeks. Thymidine analog 5-bromo-2′-deoxyuridine (BrdU) was used as a marker of cell proliferation within the dentate gyrus of the hippocampus and olfactory bulb. Results: The results of this study indicated that the total number of BrdU-positive cells in the hippocampal dentate gyrus significantly decreased with aging and were significantly fewer in the soft-diet feeding group than in hard-diet feeding group in 7-, 16- and 24-week-old rats after the BrdU injection. The change of BrdU-positive cell expression between soft and hard diets in 3- and 24-week-old rats was not observed in the olfactory bulb. Conclusion: It has been suggested that cell proliferation in the dentate gyrus of the rat hippocampus is characteristically suppressed by soft diet feeding.