Object Recognition Memory Test Research Articles

Restricting feeding to the active phase in middle-aged mice attenuates adverse metabolic effects of a high-fat diet

Time-restricted feeding ameliorates the deleterious effects of a high-fat diet on body weight and metabolism in young adult mice. Because obesity is highly prevalent in the middle-aged population, this study tested the hypothesis that time-restricted feeding alleviates the adverse effects of a high-fat diet in male middle-aged (12months) mice. C57BL6/J mice were fed one of three diets for 21–25weeks: 1) high-fat diet (60% total calories from fat) ad-libitum (HFD-AL), 2) HFD, time-restricted feeding (HFD-TRF), and 3) low-fat diet (10% total calories from fat) ad-libitum (LFD-AL) (n=15 each). HFD-TRF mice only had food access for 8h/day during their active period. HFD-TRF mice gained significantly less weight than HFD-AL mice (~20% vs 55% of initial weight, respectively). Caloric intake differed between these groups only during the first 8weeks and accounted for most but not all of their body weight difference during this time. TRF of a HFD lowered glucose tolerance in terms of incremental area under the curve (iAUC) (p<0.02) to that of LFD-AL mice. TRF of a HFD lowered liver weight (p<0.0001), but not retroperitoneal or epididymal fat pad weight, to that of LFD-AL mice. Neither HFD-AL nor HFD-TRF had any effect on performance in the novel object recognition or object location memory tests. Circulating corticosterone levels either before or after restraint stress were not affected by diet. In conclusion, TRF without caloric restriction is an effective strategy in middle-aged mice for alleviating the negative effects of a HFD on body weight, liver weight, and glucose tolerance.

Adult forebrain NMDA receptors gate social motivation and social memory

Motivation to engage in social interaction is critical to ensure normal social behaviors, whereas dysregulation in social motivation can contribute to psychiatric diseases such as schizophrenia, autism, social anxiety disorders and post-traumatic stress disorder (PTSD). While dopamine is well known to regulate motivation, its downstream targets are poorly understood. Given the fact that the dopamine 1 (D1) receptors are often physically coupled with the NMDA receptors, we hypothesize that the NMDA receptor activity in the adult forebrain principal neurons are crucial not only for learning and memory, but also for the proper gating of social motivation. Here, we tested this hypothesis by examining sociability and social memory in inducible forebrain-specific NR1 knockout mice. These mice are ideal for exploring the role of the NR1 subunit in social behavior because the NR1 subunit can be selectively knocked out after the critical developmental period, in which NR1 is required for normal development. We found that the inducible deletion of the NMDA receptors prior to behavioral assays impaired, not only object and social recognition memory tests, but also resulted in profound deficits in social motivation. Mice with ablated NR1 subunits in the forebrain demonstrated significant decreases in sociability compared to their wild type counterparts. These results suggest that in addition to its crucial role in learning and memory, the NMDA receptors in the adult forebrain principal neurons gate social motivation, independent of neuronal development.

1950 MHz radiofrequency electromagnetic fields do not aggravate memory deficits in 5xFAD mice.

The increased use of mobile phones has generated public concern about the impact of radiofrequency electromagnetic fields (RF‐EMF) on health. In the present study, we investigated whether RF‐EMFs induce molecular changes in amyloid precursor protein (APP) processing and amyloid beta (Aβ)‐related memory impairment in the 5xFAD mouse, which is a widely used amyloid animal model. The 5xFAD mice at the age of 1.5 months were assigned to two groups (RF‐EMF‐ and sham‐exposed groups, eight mice per group). The RF‐EMF group was placed in a reverberation chamber and exposed to 1950 MHz electromagnetic fields for 3 months (SAR 5 W/kg, 2 h/day, 5 days/week). The Y‐maze, Morris water maze, and novel object recognition memory test were used to evaluate spatial and non‐spatial memory following 3‐month RF‐EMF exposure. Furthermore, Aβ deposition and APP and carboxyl‐terminal fragment β (CTFβ) levels were evaluated in the hippocampus and cortex of 5xFAD mice, and plasma levels of Aβ peptides were also investigated. In behavioral tests, mice that were exposed to RF‐EMF for 3 months did not exhibit differences in spatial and non‐spatial memory compared to the sham‐exposed group, and no apparent change was evident in locomotor activity. Consistent with behavioral data, RF‐EMF did not alter APP and CTFβ levels or Aβ deposition in the brains of the 5xFAD mice. These findings indicate that 3‐month RF‐EMF exposure did not affect Aβ‐related memory impairment or Aβ accumulation in the 5xFAD Alzheimer's disease model. Bioelectromagnetics. 37:391–399, 2016. © 2016 The Authors Bioelectromagnetics published by Wiley Periodicals, Inc. on behalf of Bioelectromagnetics Society.

Further Advances in Optimizing (2-Phenylcyclopropyl)methylamines as Novel Serotonin 2C Agonists: Effects on Hyperlocomotion, Prepulse Inhibition, and Cognition Models.

A series of novel compounds with two halogen substituents have been designed and synthesized to further optimize the 2-phenylcyclopropylmethylamine scaffold in the quest for drug-like 5-HT2C agonists. Compound (+)-22a was identified as a potent 5-HT2C receptor agonist, with good selectivity against the 5-HT2B and the 5-HT2A receptors. ADMET assays showed that compound (+)-22a possessed desirable properties in terms of its microsomal stability, and CYP and hERG inhibition, along with an excellent brain penetration profile. Evaluation of (+)-22a in animal models of schizophrenia-related behaviors revealed that it had a desirable activity profile, as it reduced d-amphetamine-stimulated hyperlocomotion in the open field test, it restored d-amphetamine-disrupted prepulse inhibition, it induced cognitive improvements in the novel object recognition memory test in NR1-KD animals, and it produced very little catalepsy relative to haloperidol. These data support the further development of (+)-22a as a drug candidate for the treatment of schizophrenia.

The effects of prolonged administration of norepinephrine reuptake inhibitors on long-term potentiation in dentate gyrus, and on tests of spatial and object recognition memory in rats

Phasic norepinephrine (NE) release events are involved in arousal, novelty detection and in plasticity processes underlying learning and memory in mammalian systems. Although the effects of phasic NE release events on plasticity and memory are prevalently documented, it is less understood what effects chronic NE reuptake inhibition and sustained increases in noradrenergic tone, might have on plasticity and cognitive processes in rodent models of learning and memory. This study investigates the effects of chronic NE reuptake inhibition on hippocampal plasticity and memory in rats. Rats were administered NE reuptake inhibitors (NRIs) desipramine (DMI; 0, 3, or 7.5mg/kg/day) or nortriptyline (NTP; 0, 10 or 20mg/kg/day) in drinking water. Long-term potentiation (LTP; 200Hz) of the perforant path-dentate gyrus evoked potential was examined in urethane anesthetized rats after 30–32days of DMI treatment. Short- (4-h) and long-term (24-h) spatial memory was tested in separate rats administered 0 or 7.5mg/kg/day DMI (25–30days) using a two-trial spatial memory test. Additionally, the effects of chronically administered DMI and NTP were tested in rats using a two-trial, Object Recognition Test (ORT) at 2- and 24-h after 45 and 60days of drug administration. Rats administered 3 or 7.5mg/kg/day DMI had attenuated LTP of the EPSP slope but not the population spike at the perforant path-dentate gyrus synapse. Short- and long-term memory for objects is differentially disrupted in rats after prolonged administration of DMI and NTP. Rats that were administered 7.5mg/kg/day DMI showed decreased memory for a two-trial spatial task when tested at 4-h. In the novel ORT, rats receiving 0 or 7.5mg/kg/day DMI showed a preference for the arm containing a Novel object when tested at both 2- and 24-h demonstrating both short- and long-term memory retention of the Familiar object. Rats that received either dose of NTP or 3mg/kg/day DMI showed impaired memory at 2-h, however this impairment was largely reversed at 24-h. Animals in the high-dose NTP (20mg/kg/day) group were impaired at both short- and long-term intervals. Activity levels, used as an index of location memory during the ORT, demonstrated that rats receiving DMI were again impaired at retaining memory for location. DMI dose-dependently disrupts LTP in the dentate gyrus of anesthetized rats and also disrupts memory for tests of spatial memory when administered for long periods.

Perirhinal cortex lesions impair tests of object recognition memory but spare novelty detection.

The present study examined why perirhinal cortex lesions in rats impair the spontaneous ability to select novel objects in preference to familiar objects, when both classes of object are presented simultaneously. The study began by repeating this standard finding, using a test of delayed object recognition memory. As expected, the perirhinal cortex lesions reduced the difference in exploration times for novel vs. familiar stimuli. In contrast, the same rats with perirhinal cortex lesions appeared to perform normally when the preferential exploration of novel vs. familiar objects was tested sequentially, i.e. when each trial consisted of only novel or only familiar objects. In addition, there was no indication that the perirhinal cortex lesions reduced total levels of object exploration for novel objects, as would be predicted if the lesions caused novel stimuli to appear familiar. Together, the results show that, in the absence of perirhinal cortex tissue, rats still receive signals of object novelty, although they may fail to link that information to the appropriate object. Consequently, these rats are impaired in discriminating the source of object novelty signals, leading to deficits on simultaneous choice tests of recognition.

The effect of combined treatment with escitalopram and risperidone on the MK-801-induced changes in the object recognition test in mice.

Atypical antipsychotic drugs have some efficacy in alleviating the negative and some cognitive symptoms of schizophrenia but those effects are small and mechanisms of this action are still unknown. A few clinical reports have suggested that the antidepressant drugs, especially selective serotonin reuptake inhibitors (SSRI) are able to augment the activity of atypical antipsychotic drugs, thus effectively improving treatment of the negative and some cognitive symptoms of schizophrenia. In the present study, we evaluated the effect of escitalopram (SSRI) and risperidone (an atypical antipsychotic drug), given separately or jointly, on the effect of MK-801 (a NMDA receptor antagonist) given before to the first introductory session, in the object recognition memory test. The mice were tested for the ability to discriminate between an old, familiar and a novel object. Escitalopram and risperidone were given 30min before MK-801, and MK-801 was administered 30min before the first introductory session. Memory retention was evaluated 90min after the introductory session. The obtained results showed that MK-801 (0.2mg/kg) decreased memory retention when given before the introductory session. Risperidone at a higher dose (0.1mg/kg) reversed that effect. Co-treatment with an ineffective dose of risperidone (0.01mg/kg) and escitalopram (5 or 10mg/kg) abolished the deficit of object recognition memory induced by MK-801. The obtained results suggest that escitalopram may enhance the antipsychotic-like effect of risperidone in the animal tests used for evaluation of some cognitive symptoms of schizophrenia.

Behavioral effects of deep brain stimulation of the anterior nucleus of thalamus, entorhinal cortex and fornix in a rat model of Alzheimer's disease.

Background:Recent clinical and preclinical studies have suggested that deep brain stimulation (DBS) can be used as a tool to enhance cognitive functions. The aim of the present study was to investigate the impact of DBS at three separate targets in the Papez circuit, including the anterior nucleus of thalamus (ANT), the entorhinal cortex (EC), and the fornix (FX), on cognitive behaviors in an Alzheimer's disease (AD) rat model.Methods:Forty-eight rats were subjected to an intrahippocampal injection of amyloid peptides 1-42 to induce an AD model. Rats were divided into six groups: DBS and sham DBS groups of ANT, EC, and FX. Spatial learning and memory were assessed by the Morris water maze (MWM). Recognition memory was investigated by the novel object recognition memory test (NORM). Locomotor and anxiety-related behaviors were detected by the open field test (OF). By using two-way analysis of variance (ANOVA), behavior differences between the six groups were analyzed.Results:In the MWM, the ANT, EC, and FX DBS groups performed differently in terms of the time spent in the platform zone (F(2,23) = 6.04, P < 0.01), the frequency of platform crossing (F(2,23) = 11.53, P < 0.001), and the percent time spent within the platform quadrant (F(2,23) = 6.29, P < 0.01). In the NORM, the EC and FX DBS groups spent more time with the novel object, although the ANT DBS group did not (F(2,23) = 10.03, P < 0.001). In the OF, all of the groups showed a similar total distance moved (F(1,42) = 1.14, P = 0.29) and relative time spent in the center (F(2,42) = 0.56, P = 0.58).Conclusions:Our results demonstrated that DBS of the EC and FX facilitated hippocampus-dependent spatial memory more prominently than ANT DBS. In addition, hippocampus-independent recognition memory was enhanced by EC and FX DBS. None of the targets showed side-effects of anxiety or locomotor behaviors.

Somatostatin Receptor Subtype‐4 Agonist Enhances Memory in Apo‐E4 knock‐in Mice

This study assessed the impact of somatostatin receptor subtype‐4 (SSTR4) agonist NNC 26‐9100 on learning, memory, cortical neprilysin activity, and blood chemistries in ApoE3 and ApoE4 knock‐in mice. Twelve‐month old ApoE3 and E4 mice were treated with NNC 26‐9100 (10 mg/kg, i.p. daily for 28 days) with all comparisons made to respective vehicle control groups (n=7‐8/group). Statistical significance set at P&lt;0.05. ApoE4 mice, but not ApoE3 mice, spent more time with the novel object (object recognition memory test, day‐28) with NNC 26‐9100 treatment. T‐maze evaluation identified no significant change in learning (day‐21) or memory (day‐28) in either ApoE3 or ApoE4 mice with NNC 26‐9100 treatment. An enhancement in neprilysin activity was found in ApoE3 mice, but not ApoE4 mice, treated with NNC 26‐9100 treatment. Blood chemistries showed enhanced high density lipoprotein (HDL) levels and reduced non‐HDL levels in ApoE4 mice, but not ApoE3 mice, with NNC 26‐9100 treatment. No changes in glucose, insulin, total cholesterol, or triglycerides in either ApoE3 or E4 mice with NNC 26‐9100 treatment.These data show SSTR4 agonist NNC 26‐9100 can mitigate some forms of memory deficit associated with the ApoE4 genotype, but may do so independently of neprilysin activity. Moreover, SSTR4 agonist action enhanced the beneficial HDL levels and reduced the detrimental non‐HDL levels. This work was supported by Southern Illinois University Edwardsville STEP grant.

The Role of Peroxisome Proliferator-activated Receptor Gamma in Insulin Resistance Enhanced Alzheimer Disease Pathophysiology.

Background Alzheimer's disease (AD) shares Pathophysiological features with type 2 diabetes (T2D). The nuclear receptor peroxisome Proliferator- activated receptor GAMMA (PPARγ) is a ligand- activated transcription factor that regulates glucose and lipid metabolism and suppress inflammatory gene expression. Aim and hypothesis The potential therapeutic role of PPARγ on cognitive impairment and visuospatial memory in insulin resistance-induced AD using Pioglitazone; a PPARγ agonist. Methods AD was induced in 6 weeks old male rats by adding 6mg/L copper sulphate to drinking water for 8 weeks. Rats were randomly divided into 4 groups(n=10). (1) Normal control group on plain water, (2) AD control group, (3) Fructose drinking induced insulin resistance (IR) AD group, (4) Pioglitazone-treated group received orally (10mg/kg/day) at a volume of 2 ml/kg/day for the last 12 weeks of the 16 weeks period. Groups (3),(4) received 10% fructose solution in drinking water for 16 weeks after developing AD. Cognitive functions were assessed using discrimination index (DI) in object recognition test (ORT) and escape latency in Morris water maze(MWM) test. PPARγ was investigated for its role on γ-secretase and α secretes as well as glucose homeostasis. Results PPARγ level was significantly elevated in IR-induced rats. However, Pioglitazone treatment was associated with restoration of PPARγ level to approximately normal values. Moreover, IR produced significant reduction in DI and prolongation of escape latency. Activation of PPARγ through Pioglitazone showed significant improvement in IR-induced dysfunctions in cognitive function and visuospatial memory in ORT and MWM tasks. Conclusion PPAR γ agonists have a therapeutic potential in AD

Mammilliothalamic tract lesions disrupt tests of visuo-spatial memory.

The mammillary bodies and their projections via the mammilliothalamic tract to the anterior thalamic nuclei are known to be important for spatial memory in rodents, but their precise role remains unclear. To determine whether transection of the mammilliothalamic tract can produce deficits on tests of spatial memory even when the navigational demands placed on the animal are limited, rats with discrete mammilliothalamic tract lesions were tested on the ability to use distal visual cues to discriminate between 2 locations within a room, irrespective of the direction traveled (Experiment 1). Animals with mammilliothalamic tract lesions acquired this task more slowly and less accurately than control animals. Consistent with this impairment in discriminating different spatial locations, the same lesions also severely disrupted object-in-place memory but spared performance on standard tests of object recognition memory (Experiment 2). Finally, to compare performance on a task that is known to be sensitive to mammilliothalamic transection and requires animals to actively navigate within their environment, the effect of the lesions on spatial working memory in the radial-arm maze was examined. Taken together, the results suggest that even when there are little or no navigational demands, mammilliothalamic tract damage still results in impoverished encoding of spatial location.

Effect of general anesthesia in infancy on long-term recognition memory in humans and rats.

Anesthesia in infancy impairs performance in recognition memory tasks in mammalian animals, but it is unknown if this occurs in humans. Successful recognition can be based on stimulus familiarity or recollection of event details. Several brain structures involved in recollection are affected by anesthesia-induced neurodegeneration in animals. Therefore, we hypothesized that anesthesia in infancy impairs recollection later in life in humans and rats. Twenty eight children ages 6-11 who had undergone a procedure requiring general anesthesia before age 1 were compared with 28 age- and gender-matched children who had not undergone anesthesia. Recollection and familiarity were assessed in an object recognition memory test using receiver operator characteristic analysis. In addition, IQ and Child Behavior Checklist scores were assessed. In parallel, thirty three 7-day-old rats were randomized to receive anesthesia or sham anesthesia. Over 10 months, recollection and familiarity were assessed using an odor recognition test. We found that anesthetized children had significantly lower recollection scores and were impaired at recollecting associative information compared with controls. Familiarity, IQ, and Child Behavior Checklist scores were not different between groups. In rats, anesthetized subjects had significantly lower recollection scores than controls while familiarity was unaffected. Rats that had undergone tissue injury during anesthesia had similar recollection indices as rats that had been anesthetized without tissue injury. These findings suggest that general anesthesia in infancy impairs recollection later in life in humans and rats. In rats, this effect is independent of underlying disease or tissue injury.

Green tea ameliorates recognition memory defects in acute radiation syndrome caused by gamma irradiation

An evidence suggests that even low-dose irradiation can lead to progressive cognitive decline as well as memory deficits in both humans and experimental animals in part due to hippocampal dysfunction. To determine whether or not green tea (GT) and epigallocatechin gallate (EGCG) could attenuate memory impairment as well as suppress hippocampal neurogenesis, passive avoidance and object recognition memory test as well as TUNEL assay and immunohistochemical detection with markers of neurogenesis (Ki-67 and doublecortin (DCX)) were performed using adult mice treated with relatively low-dose gamma irradiation (2.0 Gy). GT was administered intraperitonially at a dosage of 50 mg/kg of body weight at 36 and 12 hr pre-irradiation and at 30 minutes post-irradiation, or orally at a dosage of 250 mg/kg of body weight/day for 7 days before autopsy. EGCG (25 mg/kg of body weight) was administered intraperitonially at 36 and 12 hr pre-irradiation and at 30 minutes post-irradiation. In the passive avoidance and object recognition memory test, mice trained for 1 day after acute irradiation (2 Gy) showed significant memory deficits compared with sham controls. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus increased by 12 h after irradiation. In addition, the numbers of Ki-67- and DCX-positive cells significantly decreased. GT treatment prior to irradiation attenuated memory defects, blocked apoptotic death, as well as reduced the number of DCX-positive cells. Therefore, GT may attenuate memory defects in adult mice exposed to a relatively low dose of radiation possibly by inhibiting the detrimental effects of irradiation on hippocampal neurogenesis.

HOE-140, an antagonist of B2 receptor, protects against memory deficits and brain damage induced by moderate lateral fluid percussion injury in mice

There are evidences indicating the role of kinins in pathophysiology of traumatic brain injury, but little is known about their action on memory deficits. Our aim was to establish the role of bradykinin receptors B₁ (B₁R) and B₂ (B₂R) on the behavioral, biochemical, and histologic features elicited by moderate lateral fluid percussion injury (mLFPI) in mice. The role of kinin B₁ and B₂ receptors in brain damage, neuromotor, and cognitive deficits induced by mLFPI, was evaluated by means of subcutaneous injection of B₂R antagonist (HOE-140; 1 or 10 nmol/kg) or B₁R antagonist (des-Arg9-[Leu8]-bradykinin (DAL-Bk; 1 or 10 nmol/kg) 30 min and 24 h after brain injury. Brain damage was evaluated in the cortex, being considered as lesion volume, inflammatory, and oxidative damage. The open field and elevated plus maze tests were performed to exclude the nonspecific effects on object recognition memory test. Our data revealed that HOE-140 (10 nmol/kg) protected against memory impairment. This treatment attenuated the brain edema, interleukin-1β, tumor necrosis factor-α, and nitric oxide metabolites content elicited by mLFPI. Accordingly, HOE-140 administration protected against the increase of nicotinamide adenine dinucleotide phosphate oxidase activity, thiobarbituric-acid-reactive species, protein carbonylation generation, and Na⁺ K⁺ ATPase inhibition induced by trauma. Histologic analysis showed that HOE-140 reduced lesion volume when analyzed 7 days after brain injury. This study suggests the involvement of the B₂ receptor in memory deficits and brain damage caused by mLFPI in mice.

The differential effects of chronic imipramine or citalopram administration on physiological and behavioral outcomes in naïve mice

Tricyclics and selective serotonin reuptake inhibitors (SSRIs) are probably the most widely employed reference antidepressants in animal studies on depression. Using imipramine and citalopram, we sought to assess which drug would be more appropriate as pharmacological reference in paradigms of depression in C57BL6N mice by measuring their effect on liquid consumption, home cage activity, body weight and long-term memory in naïve animals treated with each compound at generally used dose of 15mg/kg/day. Continuous logging of home cage movement, weekly monitoring of vertical activity in a novel cage, and body weight was recorded during four-week treatment period and for four weeks after discontinuation of the antidepressant; sucrose preference was evaluated at weekly intervals during drug administration. A novel object recognition memory test was performed in mice treated the antidepressants for two weeks. Compared to control, imipramine-treated mice displayed increased sucrose and water intake, as well as enhanced home-cage and novelty exploration activities, and reduced body weight. Imipramine also impaired learning in the object recognition task, but citalopram diminished object exploration sufficiently to invalidate the test. Citalopram-treated animals demonstrated no changes in a sucrose test and had elevated body mass. Thus basic physiological and behavioral outcomes in naïve mice were significantly altered by the chronic administration of imipramine and, to a lesser extent, citalopram. As altered variables are crucial for the evaluation of antidepressant-like effects in mice, our data suggest that, at commonly used doses, both drugs must be applied in mouse models of depression with caution.

Knockout of c-Jun N-terminal kinases 1, 2 or 3 isoforms induces behavioural changes

c-Jun N-terminal kinases (JNKs) are central and ubiquitous mediators of cellular signaling for both physiogical-regenerative and pathological-apoptotic processes. Their impact on degeneration or inflammation is well documented, but so far little is known about their roles in higher brain functions. The more, the contribution of individual JNK isoforms remains obscure so far.Here we have tested the behaviour of JNK1, JNK2 and JNK3 knockout (ko) mice in elevated plus maze (EPM), open field (OF), novel object recognition memory (NORM) test and Morris water maze (MWM). Compared with wild type C57BL/6N mice JNK ko mice revealed significant differences. Taken together the data on anxiety, exploration and learning indicate that JNK1 ko mice displayed a stronger explorative behaviour and that knockout of JNK2 or JNK3 showed a tendency of behaviour opposite to that of JNK1 ko mice. This pattern reminds of the impact of individual JNK ko on neurodegeneration. This is the first comparative study on the impact of individual JNK ko on behavioural parameters.

Effects of prolonged agmatine treatment in aged male Sprague–Dawley rats

Increasing evidence suggests that altered arginine metabolism contributes to cognitive decline during ageing. Agmatine, decarboxylated arginine, has a variety of pharmacological effects, including the modulation of behavioural function. A recent study demonstrated the beneficial effects of short-term agmatine treatment in aged rats. The present study investigated how intraperitoneal administration of agmatine (40mg/kg, once daily) over 4–6weeks affected behavioural function and neurochemistry in aged Sprague–Dawley rats. Aged rats treated with saline displayed significantly reduced exploratory activity in the open field, impaired spatial learning and memory in the water maze and object recognition memory relative to young rats. Prolonged agmatine treatment improved animals’ performance in the reversal test of the water maze and object recognition memory test, and significantly suppressed age-related elevation in nitric oxide synthase activity in the dentate gyrus of the hippocampus and prefrontal cortex. However, this prolonged supplementation was unable to improve exploratory activity and spatial reference learning and memory in aged rats. These findings further demonstrate that exogenous agmatine selectively improves behavioural function in aged rats.

방사선 유도 학습기억 장애에 대한 diethyldithiocarbamate의 효과

Evidence suggests that even low-dose irradiation can lead to progressive cognitive decline and memory deficits, which implicates, in part, hippocampal dysfunction in both humans and experimental animals. This study examined whether diethyldithiocarbamate (DDC) could attenuate memory impairment, using passive avoidance and object recognition test, and suppression of hippocampal neurogenesis, using the TUNEL assay and immunohistochemical detection with markers of neurogenesis (Kiel 67 (Ki-67) and doublecortin (DCX)) in adult mice treated with gamma radiation (0.5 or 2 Gy). DDC was administered intraperitonially at a dosage of 1,000 of body weight at 30 min. before irradiation. In passive avoidance and object recognition memory test, the mice, trained for 1 day after acute irradiation (2 Gy) showed significant memory deficits compared with the sham controls. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus (DG) was increased 12 h after irradiation. In addition, the number of Ki-67- and DCX-positive cells were significantly decreased. DDC treatment prior to irradiation attenuated the memory defect, and blocked the apoptotic death. DDC may attenuate memory defect in a relatively low-dose exposure of radiation in adult mice, possibly by inhibiting a detrimental effect of irradiation on hippocampal neurogenesis.

Abstract SY31-02: Behavioral consequences of peripheral tumors: Neuroimmune mechanisms

Abstract SY31-02: Behavioral consequences of peripheral tumors: Neuroimmune mechanisms

Fast neutron irradiation deteriorates hippocampus-related memory ability in adult mice

Object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice exposed to cranial fast neutron irradiation (0.8 Gy) were examined to evaluate hippocampus-related behavioral dysfunction following acute exposure to relatively low doses of fast neutrons. In addition, hippocampal neurogenesis changes in adult murine brain after cranial irradiation were analyzed using the neurogenesis immunohistochemical markers Ki-67 and doublecortin (DCX). In the object recognition memory test and contextual fear conditioning, mice trained 1 and 7 days after irradiation displayed significant memory deficits compared to the sham-irradiated controls. The number of Ki-67- and DCX-positive cells decreased significantly 24 h post-irradiation. These results indicate that acute exposure of the adult mouse brain to a relatively low dose of fast neutrons interrupts hippocampal functions, including learning and memory, possibly by inhibiting neurogenesis.