DHA Depletion in Rat Brain Is Associated With Impairment on Spatial Learning and Memory

Objective To examine the effect of docosahexaenoic acid （DHA） deficiency in brain on spatial learning and memory in rats. Methods Sprague Dawley rats were fed with an n-3 fatty acid deficient diet for two generations to induce DHA depletion in brain, DHA in seven brain regions was analyzed using the gas-liquid chromatography. Morris water maze （MWM） was employed as an assessing index of spatial learning and memory in the n-3 fatty acid deficient adult rats of second generation. Results Feeding an n-3 deficient diet for two generations depleted DHA differently by 39%-63% in the seven brain regions including cerebellum, medulla, hypothalamus, striatum, hippocampus, cortex and midbrain, The MWM test showed that the n-3 deficient rats took a longer time and swam a longer distance to find the escape platform than the n-3 Adq group. Condusion The spatial learning and memory in adult rats are partially impaired by brain DHA depletion.

Effect of tetramethylpyrazine on the spatial learning and memory function of rats after focal cerebral ischemia

BACKGROUND： Tetramethylpyrazine （TMP） presents the effect of anti-platelet aggregation, reduces arteria resistance, increases cerebral blood flow, and improves microcirculation. OBJECTIVE： To observe the effects of TMP on the learning and memory abilities and the number of neurons in cortex and hippocampus after focal cerebral ischemia in rats DESIGN： A randomized controlled tria SETTING： Department of Human Anatomy and Histological Embryology, School of Medicine, Xi＇an Jiaotong University. MATERIALS： Fifty adult male Sprague-Dawley rats, weighing 250-300 g were supplied by the Experimental Animal Center, School of Medicine, Xi＇an Jiaotong University. TMP was purchased from Wuxi Seventh Pharmaceutical Co.Ltd （Lot Number： 2004051106, Specification： 2 mL/piece）. METHODS ： The experiments were carried out in School of Medicine of Xi＇an Jiaotong University from June 2004 to May 2005. The 50 rats were randomly divided into five groups according to the random number table method： sham-operated group, cerebral ischemia control group, low-dose TMP group, middle-dose TMP group and high-dose TMP group, 10 rats in each group. Rats in the TMP groups were immediately treated with intraperitoneal injection of TMP of 40, 80 and 120 mg/kg respectively, and those in the sham-operated group and cerebral ischemia control group were injected intraperitoneally by isovolume saline, once a day for 14 days successively. On the 15^th day, the spatial learning and memory abilities of the rats were assessed with the Morris water maze test, and then the changes of neuron numbers in cortex and hippocampus were observed by Nissl staining of brain sections. MAIN OUTCOME MEASURES ： The results of Morris water maze test and the changes of neuron numbers in cortex and hippocampus by Nissl staining of brain sections were observed. RESULTS： Finally 39 rats were involved in the analysis of results, and the other 11 died of excessive anesthesia or failure in model establishment. ① The rats in the cerebral ischemia control group manifested obvious spatial cognitive deficits in the place navigation trial and spatial probe trial. The mean values of escape latency in the sham-operated group, low, middle and high-dose TMP groups were obviously shorter than that in the cerebral ischemia control group [（23.92±2.21）, （41.84±3.74）, （39.50 ±3.80）, （31.38_±3.72）, （61.60±3.61） s, P 〈 0.05-0.01]. In the spatial probe trial, significant differences in the percentage of time spending in the former platform quadrant and frequency of crossing the former platform site in the sham-operated group, lose, middle and high-dose TMP groups were obviously higher or more than those in the cerebral ischemia control group [（36.27±3.42） %, （35.84±2.54）%, （38.43±3.08）%, （36.51±1.96）%, （22.24±3.46）%; （11 ±1 ）, （10±1）, （8_±1）, （8±1）, （4±1） times, P 〈 0.01]. ② In the morphological observation, the numbers of neurons in ipsilateral （left） parietal cortex in the sham-operated group, low, middle and high-dose TMP groups were obviously more than that in the cerebral ischemia control group [（98±8）, （65±5）, （53±6）, （57±6）, （37±6）/0.625 mm^2, P 〈 0.01], but the number of neurons in left hippocampus had no obvious differences among the groups （P 〉 0.05）. CONCLUSION ： TMP can improve obviously the spatial learning and memory function after permanent focal cerebral ischemia in rats, and the neuroprotective role of the drug in cortex may be involved in its mechanism.

Effects of butternut squash extract on dentate gyrus cell proliferation and spatial learning in male adult rats

Previous studies reported that some plants, including butternut squash, exert positive effects on the brain. However, few studies have examined the effects of butternut squash on learning, memory, and neurogenesis. This study studied the effects of butternut squash extract on spatial learning and cell proliferation in the dentate gyrus of healthy male rats. Thirty-five male Wistar rats were intraperitoneally injected with 0, 50, 100, 200 and 400 mg/kg butternut squash extract once daily for 2 months. After the last administration, rat＇s spatial memory was studied using the Morris water maze. Finally, rats were sacrificed and hippocampal sections were prepared for light microscopy and bromodeoxyuridine immunohistochemistry studies. The results revealed that escape latency and swim distance decreased in all treatment groups compared with the control rats, and that the number of bromodeoxyuridine-positive cells in the dentate gyrus was significantly increased in the treatment groups compared with the controls. These findings suggest that butternut squash extract improves the learning and memory abilities of male rats, and increases the proliferation of dentate gyrus cells.

Effect of calcitonin gene-related peptide and nerve growth factor on spatial learning and memory abilities of rats following focal cerebral ischemia/reperfusion

BACKGROUND: Calcitonin gene-related peptide (CGRP) and nerve growth actor (NGF) cam improve spatial learning and memory abilities of rats with cerebral ischemia/reperfusion; however, the effect of combination of them on relieving learning and memory injury following cerebral ischemia/reperfusion should be further studied. OBJECTIVE: To study the effects of exogenous CGRP and NGF on learning and memory abilities of rats with focal cerebral ischemia/reperfusion. DESIGN: Randomized controlled animal study. SETTING: Department of Neurosurgery, the Second Hospital of Xiamen; Department of Neurosurgery, the Second Affiliated Hospital of China Medical University; Department of Neurobiology, Basic Medical College of China Medical University. MATERIALS: A total of 30 healthy male SD rats, aged 8 weeks, of clean grade, weighing 250-300 g, were provided by Experimental Animal Department of China Medical University. All rats were randomly divided into sham-operation group, ischemia/reperfusion group and treatment group with 10 in each group. The main reagents were detailed as the follows: 100 g/L chloral hydrate, 0.5 mL CGRP (2 mg/L, Sigma Company, USA), and NGF (1× 106 U/L, 0.5 mL, Siweite Company, Dalian). METHODS: The experiment was carried out in the Department of Neurobiology, Basic Medical College of China Medical University from February to July 2005. Rat models of middle cerebral artery occlusion were established by method of occlusion, 2 hours after that rats were anesthetized and the thread was slightly drawn out for 10 mm under direct staring to perform reperfusion. Rats in the ischemia/reperfusion group received intraperitoneal injection of 1 mL saline via the abdomen at two hours later, while rats in the treatment group at 2 hours later received intraperitoneal injection of 2 mg/L CGRP (0.5 mL) and 1×106 U/L NGF (0.5 mL) once a day for 10 successive days. First administration was accomplished within 15 minutes after ischemia/reperfusion. Rats in the sham-operation group were separated of the vessels without occlusion or administration. The neural function was evaluated with Zea Longa 5-grade scale. Animals with the score of one, two and three points received Morris water-maze test to measure searching time on platform (omitting platform-escaping latency). Meanwhile, leaning and memory abilities of animals were reflected through testing times of passing through platform per minute. MAIN OUTCOME MEASURES: Experimental results of omitting platform-escaping latency and spatial probe. RESULTS: Three and two rats in the ischemia/reperfusion group and treatment group respectively were not in accordance with the criteria in the process, and the rest were involved in the final analysis. ① Comparisons of platform-escaping latency during Morris water-maze test in all the three groups: Ten days after modeling, the platform-escaping latency in the ischemia/reperfusion group was obviously longer than that in sham-operation group (P < 0.01), and was significantly shorter than that in the treatment group (P < 0.01). ② Comparisons of times of passing through platform in all the three groups: Times of passing through platform were remarkably less in the ischemia/reperfusion group than those in the sham-operation group [(1.79±0.39), (4.30±0.73) times/minute, P < 0.01], and those were markedly more in the treatment group than the ischemia/reperfusion group [(3.16±1.03), (1.79±0.39) times/minute, P < 0.01]. CONCLUSION: CGRP and NGF are capable of ameliorating the abilities of spatial learning and memory in MCAO rats, which indicates that CGRP and NGF can protect ischemic neurons.

Developmental Effects of Malathion Exposure on Recognition Memory and Spatial Learning in Males Wistar Rats

Most cognitive effects of Organophosphate Pesticides (OP) are induced after exposure to parathion, chlorpyrifos and diazinon, which the usage has been restricted because of overt signs of their toxicities. In this study, we investigate whether developmental exposure to Malathion could impair spatial learning and recognition memory in male rats. Animals exposed by intragastric route, from in utero to young adult stage, to incremental doses of Malathion dissolved in corn oil;100, 200 and 300 mg/kg of body weight, and one control group are given corn oil. Then, cognitive and behaveioral abilities are assessed using Barnes maze and object recognition memory task. Malathion administration at 300 mg/kg is toxic to pregnant dams, and pups are stillborns. Rats exposed to 200 mg/kg make a significant working memory error, and require more time to find an escape box during the initial training phase of Barnes maze. However, fewer errors are made in rats exposed to 100 mg/kg. For reversal learning task, the high dose group shows great deficits in spatial strategy to locate the new position of the box. With respect to recognition task, both dose 100 and 200 mg/kg impair significant short-term (2 h after habituation phase) object recognition memory, but long-term (24 h after habituation phase) recognition memory is intact in high dose group. The current study also reveals that all treatments induce high significant neocortex acetylcholinesterase (AChE) activity inhibition, but 100 mg/kg dose is not sufficient to disrupt great hippocampal activity alteration. These results suggest that developmental exposure to Malathion, despite low toxicity described, may induce late-emerging spatial learning and recognition memorialterations. Moreover, Cortical and hippocampal area that support strongly these behaviors remain sensitive to incremental doses of Malathion.

Thioredoxin and impaired spatial learning and memory in the rats exposed to intermittent hypoxia

Background Obstructive sleep apnea （OSA） can cause cognitive dysfunction and may be a reversible cause of cognitive loss in patients with Alzheimer＇s disease （AD）. Chronic exposure to intermittent hypoxia （IH）, such as encountered in OSA, is marked by neurodegenerative changes in rat brain. We investigated the change of thioredoxin （Trx）, spatial learning and memory in rats exposed to chronic intermittent hypoxia （CIH）. Methods Forty healthy male Sprague-Dawley （SD） rats were randomly divided into four groups of ten each： a CIH＋normal saline （CIH＋NS group）, a N-acetylcystein-treated CIH （CIH＋NAC） group, a sham CIH group （sham CIH＋NS）, and a sham NAC-treated sham CIH （CIH＋NAC） group. Spatial learning and memory in each group was assessed with the Morris water maze. Real-time PCR and Western blotting were used to examine mRNA and protein expression of Trx in the hippocampus tissue. The terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling （TUNEL） method was used to detect the apoptotic cells of the hippocampus CA1 region. Results CIH-rats showed impaired spatial learning and memory in the Morris water maze, including longer mean latencies for the target platform, reduced numbers of passes over the previous target platform and a smaller percentage of time spent in the target quadrant. Trx mRNA and protein levels were significantly decreased in the CIH-hippocampus, meanwhile, an elevated apoptotic index revealed apoptosis of hippocampal neurons of rats exposed to CIH. The rats, which acted better in the Morris water maze, showed higher levels of the Trx mRNA and protein in the hippocampus; apoptotic index of the neurons in the hippocampus of each group was negatively correlated with the Trx mRNA and protein levels. Conclusion The Trx deficit likely plays an important role in the impaired spatial learning and memory in the rats exposed to CIH and may work through the apoptosis of neurons in the hippocampus.

Effects of electroacupuncture at Guanyuan(CV 4)or Sanyinjiao(SP 6)on hypothalamus-pituitary-ovary axis and spatial learning and memory in female SAMP8 mice

OBJECTIVE: To investigate the effects of electroacupuncture(EA) at the Guanyuan(CV 4) or Sanyinjiao(SP 6) acupoints on the hypothalamus-pituitary-ovary(HPO) axis and spatial learning and memory in female mice.METHODS: Nine-month-old female mice with senescence-accelerated mouse prone 8(SAMP8)were divided into three groups: the disease model,EA-Guanyuan and EA-Sanyinjiao groups. Concurrently, 9-month old female mice with senescence-accelerated mouse resistance 1(SAMR1)were set as the control model group. The two treatment groups were given the same pattern of EA stimulation. Gonadotropin-releasing hormone, luteinizing hormone, follicle-stimulating hormone(FSH) and Serum estradiol levels in the Hypothalamus-pituitary-ovary axis were assessed by enzyme-linked immunosorbent assay to determinethe HPO axis function level. Spatial learning and memory were assessed by the Morris Water Maze(MWM) test.RESULTS:(a) HPO axis: compared with the control model group, the disease model group displayed a decrease in E2 levels(P < 0.01), and an increase in Gn RH, LH and FSH levels(P < 0.01). E2 levels were increased in EA treatment groups compared with the disease model group(P < 0.05). In contrast,Gn RH and LH and FSH levels were reduced(P <0.05). EA-Sanyinjiao group was superior than EA-Guanyuan group on increasing E2 and declining Gn RH levels(P < 0.01).(b) The MWM test demonstrated that the response latency in the EA-Sanyinjiao treatment group declined from day 2 to day5 compared with the disease model group(P <0.05), whereas the EA-Guanyuan treatment group showed no significant difference.CONCLUSION: EA can regulate hormone(E2, FSH,LH, Gn RH) levels in the HPO axis and the spatial learning and memory ability in female SAMP8 mice. Moreover, this effect may have been more pronounced in the EA-Sanyinjiao group than the EA-Guanyuan group. The underlying mechanism of the EA-induced changes may be related to gonadal hormone shifts in the HPO axis, followed by an improvement in spatial learning and memory.

Low-level lead exposure effects on spatial reference memory and working memory in rats

BACKGROUND： Studies have demonstrated that lead exposure can result in cognitive dysfunction and behavior disorders. However, lead exposure impairments vary under different experimental conditions. OBJECTIVE： To detect changes in spatial learning and memory following low-level lead exposure in rats, in Morris water maze test under the same experimental condition used to analyze lead exposure effects on various memory types and learning processes. DESIGN AND SETTING： The experiment was conducted at the Animal Laboratory, Institute of Psychology, Chinese Academy of Science between February 2005 and March 2006. One-way analysis of variance （ANOVA） and behavioral observations were performed. MATERIALS： Sixteen male, healthy, adult, Sprague Dawley rats were randomized into normal con-trol and lead exposure groups （n = 8）. METHODS： Rats in the normal control group were fed distilled water, and those in the lead exposure group were fed 250 mL of 0.05% lead acetate once per day. At day 28, all rats performed the Morris water maze test, consisting of four phases： space navigation, probe test, working memory test, and visual cue test. MAIN OUTCOME MEASURES： Place navigation in the Morris water maze was used to evaluate spatial learning and memory, probe trials for spatial reference memory, working memory test for spatial working memory, and visual cue test for non-spatial cognitive function. Perkin-Elmer Model 300 Atomic Absorption Spectrometer was utilized to determine blood lead levels in rats. RESULTS： （1） In the working memory test, the time to reach the platform remained unchanged between the control and lead exposure groups （F（1,1） = 0.007, P = 0.935）. A visible decrease in escape latencies was observed in each group （P = 0.028）. However, there was no significant difference between the two groups （F（1,1） = 1.869, P = 0.193）. The working memory probe test demonstrated no change between the two groups in the time spent in the target quadrant during the working memory probe test （F（1,1） = 1.869, P = 0.193）. However, by day 4, differences were observed in the working memory test （P 〈 0.01）. （2） Multivariate repetitive measure and ANOVA in place navigation presented no significant difference between the two groups （F（1,1） = 0.579, P = 0.459）. （3） Spatial probe test demonstrated that the time to reach the platform was significantly different between the two groups （F（1,1） = 4.587, P = 0.048）, and one-way ANOVA showed no significant difference in swimming speed between the two groups （F（1,1） = 1.528, P = 0.237）. （4） In the visual cue test, all rats reached the platform within 15 seconds, with no significant difference （F（1,1） = 0.579, P = 0.459）. （5） During experimentation, all rats increased in body mass, but there was no difference between the two groups （F（1,1） = 0.05, P = 0.943）. At day 28 of 0.05% lead exposure, the blood lead level was 29.72 μg/L in the lead exposure group and 5.86 μg/L in the control group （P 〈 0.01）. CONCLUSION： The present results revealed low-level lead exposure significantly impaired spatial reference memory and spatial working memory, but had no effect on spatial learning.

Effects of Danggui-Shaoyao-San on the Influence of Spatial Learning and Memory Induced by Experimental Tooth Movement

Background： The pain caused by orthodontic treatment has been considered as tough problems in orthodontic practice. There is substantial literature on pain which has exactly effected on learning and memory; orthodontic tooth movement affected the emotional status has been showed positive outcomes. Danggui-Shaoyao-San （DSS） is a Traditional Chinese Medicine prescription that has been used for pain treatment and analgesic effect for orthodontic pain via inhibiting the activations of neuron and glia. We raised the hypothesis that DSS could restore the impaired abilities of spatial learning and memory via regulating neuron or glia expression in the hippocampus. Methods： A total of 36 rats were randornly divided into three groups： （ 1 ） Sham group （n = 12）, rats underwent all the operation procedure except for the placement of orthodontic forces and received saline treatment： （2） experimental tooth movement （ETM） group （n - 12）, rats received saline treatment and ETM： （3） DSS ＋ ETM （DETM） group （n = 12）, rats received DSS treatment and ETM. All DETM group animals were administered with DSS at a dose of 150 mg/kg. Monis water maze test was evaluated： immunofluorescent histochemistry was used to identity astrocytes activation, and immunofluorescent dendritic spine analysis was used to identify the dendritic spines morphological characteristics expression levels in hippocampus. Results： Maze training sessions during the 5 successive days revealed that ETM significantly deficits in progressive learning in rats, DSS that was given from day 5 prior to ETM enhanced progressive learning. The ETM group rats took longer to cross target quadrant during the probe trial and got less times to cross-platform than DETM group. The spine density in hippocampus in ETM group was significantly decreased cornpared to the sham group. In addition, thin and mature spine density were decreased too. However, the DSS administration could reverse the dendritic shrinkage and increase the spine density compared to the ETM group. Astrocytes activation showed the opposite trend in hippocampus dentate gyrus （DG）. Conclusions： Treatment with DSS could restore the impaired abilities on ETM-induced decrease of learning and memory behavior. The decreased spines density in the hippocampus and astrocytes activation in DG ofhippocampus in the ETM group rats may be related with the decline of the ability of learning and rnernory. The ability to change the synaptic plasticity in hippocarnpus after DSS administration may be correlated with the alleviation of impairment of learn and memory atter ETM treatment.

Distinguishing normal brain aging from the development of Alzheimer＇s disease：inflammation,insulin signaling and cognition

As populations age, prevalence of Alzheimer＇s disease（AD） is rising. Over 100 years of research has provided valuable insights into the pathophysiology of the disease, for which age is the principal risk factor. However, in recent years, a multitude of clinical trial failures has led to pharmaceutical corporations becoming more and more unwilling to support drug development in AD. It is possible that dependence on the amyloid cascade hypothesis as a guide for preclinical research and drug discovery is part of the problem. Accumulating evidence suggests that amyloid plaques and tau tangles are evident in non-demented individuals and that reducing or clearing these lesions does not always result in clinical improvement. Normal aging is associated with pathologies and cognitive decline that are similar to those observed in AD, making differentiation of AD-related cognitive decline and neuropathology challenging. In this mini-review, we discuss the difficulties with discerning normal, age-related cognitive decline with that related to AD. We also discuss some neuropathological features of AD and aging, including amyloid and tau pathology, synapse loss, inflammation and insulin signaling in the brain, with a view to highlighting cognitive or neuropathological markers that distinguish AD from normal aging. It is hoped that this review will help to bolster future preclinical research and support the development of clinical tools and therapeutics for AD.

Scorpion venom heat-resistant protein decreases immunoreactivity of OX-42-positive microglia cells in MPTP-treated mice

BACKGROUND： Microglia function as the immune surveyors of the brain under normal physiologica conditions. However, microglia become activated in response to brain injuries and immunological OBJECTIVE： To explore the influence of scorpion venom （SV） heat-resistant protein on frontal cortex and hippocampal microglia cells in a mice model of Parkinson＇s disease. DESIGN, TIME AND SETTING： Randomized, controlled, cellular immunity study. The experiment was performed at the Physiology Department Laboratory in Dalian Medical University between June 2005 and July 2008. MATERIALS： Ninety-six healthy, C57B1/6 mice; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine （MPTP） from Sigma, USA; SV heat-resistant protein （Experimental Base Institute in Dalian Medical University）. The mice were randomly divided into four groups （n = 24）： normal control, negative control, model, and SV heat-resistant protein. METHODS： Mice in the model and SV heat-resistant protein groups were subcutaneously injected with MPTP （20 mg/kg） to model Parkinson＇s disease, while the normal control and negative control groups were injected with physiological saline in the neck for 8 successive days. In addition, mice in the model and normal control groups were intraperitoneally injected with physiological saline 2 hours following administration, while SV heat-resistant protein and negative control groups were injected SV heat-resistant protein （0.01 mg/kg）. MAIN OUTCOME MEASURES： lmmunoreactivity of microglia cells in MPTP-treated mice. RESULTS： Compared with normal control mice, MPTP-treated mice displayed increased OX-42 expression in the brain. However, in the SV heat-resistant protein-treated mice, OX-42 expression was decreased, compared to the model group. In the model mouse group, the number of OX-42-positive microglia was increased in the frontal cortex, caudatum, and hippocampal hilus, compared to the normal control mice （P 〈 0.01）. However, in the SV heat-resistant protein-treated mice, the number of OX-42-positive microglia significantly decreased in the frontal cortex, caudatum, and hippocampal hilus, compared to the model group （P 〈 0.01）. CONCLUSION： SV heat-resistant protein inhibited MPTP-induced microglial activation in the mouse frontal cortex and hippocampus, resulting in reduced microglial activation in the brain.

Rhesus monkey neural stem cell transplantation promotes neural regeneration in rats with hippocampal lesions

Rhesus monkey neural stem cells are capable of differentiating into neurons and glial cells. Therefore, neural stem cell transplantation can be used to promote functional recovery of the nervous system. Rhesus monkey neural stem cells （1 ×10^5 cells/μL） were injected into bilateral hippocampi of rats with hippocampal lesions. Confocal laser scanning microscopy demonstrated that green fluorescent protein-la- beled transplanted cells survived and grew well. Transplanted cells were detected at the lesion site, but also in the nerve fiber-rich region of the cerebral cortex and corpus callosum. Some transplanted cells differentiated into neurons and glial cells clustering along the ventricular wall, and integrated into the recipient brain. Behavioral tests revealed that spatial learning and memory ability improved, indicating that rhesus monkey neural stem cells noticeably improve spatial learning and memory abilities in rats with hippocampal lesions.

Low dose of corticosterone treatment with exercise increases hippocampal cell proliferation, and improves cognition

Intermediate level of stress is beneficial for brain functions, whereas extreme low level or high level of stress is deleterious. We have previously shown that chronic exposure to high doses of corticosterone （CORT） suppressed hippocampal plasticity and physical exercise in terms of running counteracted the detrimental effects of CORT treatment. We aimed to study whether a mild stress, that mimicked by a treatment with low CORT dose, improved hippocampal plasticity in terms of hippocampal cell proliferation and dendritic remodeling, and to examine whether running with CORT treatment showed an additive effect on improving hippocampal plasticity. The rats were treated with 20 mg/kg CORT for 14 days with or without running, followed by Morris water maze test or forced swim test. The hippocampal proliferating cells was labeled by intraperitoneal injection of 5-bromo-2＇-deoxyuridine. The dendritic morphology was analyzed using Golgi staining method. Treatment with 20 mg/kg CORT alone yielded a higher number of hippocampal cell proliferation and significantly increased dendritic branching compared to vehicle-treated non-runners, but had no behavioral effects. In contrast, CORT treatment with running showed an additive increase in hippocampal cell proliferation and dendritic remodeling that was associated with improved spatial learning and decreased depression-like behavior; however, there was no additive improvement in behavior compared to vehicle-treated runners. These findings suggest that mild stress does not always cause detrimental effect on the brain, and combining mild stress with running could promote hippocampal plasticity via inducing cell proliferation and dendritic remodeling.

Behavior of Phrynocephalus frontalis to Avoid Traps

Previous studies have shown that reptiles are capable of spatial learning and learn to locate important environmental resources so that they can return to those locations at a future time, when needed. Lizards improve their adaptability and survival by learning the position of their shelter in a complex environment. This behavior raises the question, whether lizards can sense danger, such as a trap, in their surroundings, by determining the location of the trap and avoiding it. In the present study, we used a pitfall trap to test if steppe toad-headed agama, Phrynocephalus frontalis, can learn to recognize the position of the trap and avoid it. Our results revealed that the percentage of activity time in the trap area was significantly reduced （P 〈 0.001） and the time of drop trap was also significantly reduced （P = 0.00631）. The number of burrows dug by lizards distributed in the trap area was the least. Reduced activity time in the trap area was observed to have no obvious relationship with the drop in the number of burrows. The present study, therefore, demonstrates that P. frontalis are capable of learning the avoidance of a trap by locating its position. The findings offer significant insight in the understanding of reptilian behavior, which is important in the study of the role of reptiles in global ecology, especially because they are often very sensitive to environmental changes.

The Differential Effects of Chronic Alcohol and Cigarette Smoke Exposures on Cognitive-Behavioral Dysfunction in Long Evans Rats

Background and Objective: Chronic heavy alcohol consumption and daily cigarette smoking are the most prevalent substance use problems in the U.S., including Veterans. Excessive alcohol use causes neurocognitive and behavioral deficits that can be linked to neurodegeneration. Similarly, preclinical and clinical data suggest that smoking also leads to brain atrophy. This study examines the differential and additive effects of alcohol and cigarette smoke (CS) exposures on cognitive-behavioral function. Methods: A 4-way experimental model of chronic alcohol and CS exposures was generated using 4-week-old male and female Long Evans rats that were pair-fed with Lieber-deCarli isocaloric liquid diets containing 0% or 24% ethanol for 9 weeks. Half of the rats in the control and ethanol groups were exposed to CS for 4 hours/day and 4 days/week for 9 weeks. All rats were subjected to Morris Water Maze, Open Field, and Novel Object Recognition testing in the last experimental week. Results: Chronic alcohol exposure impaired spatial learning as shown by significantly increased latency to locate the platform, and it caused anxiety-like behavior marked by the significantly reduced percentage of entries to the center of the arena. Chronic CS exposure impaired recognition memory as suggested by significantly less time spent at the novel object. Combined exposures to alcohol and CS did not show any significant additive or interactive effect on cognitive-behavioral function. Conclusion: Chronic alcohol exposure was the main driver of spatial learning, while the effect of secondhand CS exposure was not robust. Future studies need to mimic direct CS exposure effects in humans.

The combined role of visual and olfactory cues in foraging by Cataglyphis ants in laboratory mazes

Foragers use several senses to locate food,and many animals rely on vision and smell.It is beneficial not to rely on a single sense,which might fail under certain conditions.We examined the contribution of vision and smell to foraging and maze exploration under laboratory conditions using Cataglyphis desert ants as a model.Foraging intensity,measured as the number of workers entering the maze and arriving at the target as well as target arrival time,were greater when food,blue light,or both were offered or presented in contrast to a control.Workers trained to forage for a combined food and light cue elevated their foraging intensity with experience.However,foraging intensity was not higher when using both cues simultaneously than in either one of the two alone.Following training,we split between the two cues and moved either the food or the blue light to the opposite maze corner.This manipulation impaired foraging success by either leading to fewer workers arriving at the target cell(when the light stayed and the food was moved)or to more workers arriving at the opposite target cell,empty of food(when the food stayed and the light was moved).This result indicates that ant workers use both senses when foraging for food and readily associate light with food.

Comparative Study of ROCK1 and ROCK2 in Hippocampal Spine Formation and Synaptic Function

Rho-associated kinases(ROCKs)are serinethreonine protein kinases that act downstream of small Rho GTPases to regulate the dynamics of the actin cytoskeleton.Two ROCK isoforms(ROCK1 and ROCK2)are expressed in the mammalian central nervous system.Although ROCK activity has been implicated in synapse formation,whether the distinct ROCK isoforms have different roles in synapse formation and function in vivo is not clear.Here,we used a genetic approach to address this long-standing question.Both Rock1^+/- and Rock2^+/- mice had impaired glutamatergic transmission,reduced spine density,and fewer excitatory synapses in hippocampal CA1 pyramidal neurons.In addition,both Rockl^+/- and Rock2^+/- mice showed deficits in long-term potentiation at hippocampal CA1 synapses and were impaired in spatial learning and memory based on the water maze and contextual fear conditioning tests.However,the spine morphology of CA1 pyramidal neurons was altered only in Rock2^+/- but not Rock1^+/- mice.In this study we compared the roles of ROCK1 and ROCK2 in synapse formation and function in vivo for the first time.Our results provide a better understanding of the functions of distinct ROCK isoforms in synapse formation and function.