Significant Difference In Escape Latency Research Articles

Fractionated brain X-irradiation profoundly reduces hippocampal immature neuron numbers without affecting spontaneous behavior in mice

Whole brain radiotherapy (WBRT) is used to improve tumor control in patients with primary brain tumors, or brain metastasis from various primary tumors to improve tumor control. However, WBRT can lead to cognitive decline in patients. We assessed whether fractionated WBRT (fWBRT) affects spontaneous behavior of mice in automated home cages and cognition (spatial memory) using the Barnes maze.Male C57Bl/6j mice received bi-lateral fWBRT at a dosage of 4 Gy/day on 5 consecutive days. In line with previous reports, immunohistochemical analysis of doublecortin positive cells in the dentate gyrus showed a profound reduction in immature neurons 4 weeks after fWBRT. Surprisingly, spontaneous behavior as measured in automated home cages was not affected. Moreover, learning and memory measured with Barnes maze, was also not affected 4–6 weeks after fWBRT. At 10–11 weeks after fWBRT a significant difference in escape latency during the learning phase, but not in the probe test of the Barnes maze was observed.In conclusion, although we confirmed the serious adverse effect of fWBRT on neurogenesis 4 weeks after fWBRT, we did not find similar profound effects on spontaneous behavior in the automated home cage nor on learning abilities as measured by the Barnes maze. The relationship between the neurobiological effects of fWBRT and cognition seems more complex than often assumed and the choice of animal model, cognitive tasks, neurobiological parameters, and experimental set-up might be important factors in these types of experiments.

Safety assessment of multiple repeated percutaneous punctures for the collection of cerebrospinal fluid in rats.

The objective of this study was to examine the safety of multiple repeated percutaneous punctures of cisterna magna for collecting cerebrospinal fluid (CSF) and preliminarily determine the optimal time interval and volume at each collection. Sixty Wistar rats were randomly assigned to six groups: 10 d-0 μL, 10 d-100 μL (100 μL CSF collected at an interval of 10 days), 10 d-150 μL, 15 d-0 μL, 15 d-100 μL, and 15 d-150 μL. CSF was collected by percutaneous puncture of the cisterna magna at four time-points. Simultaneously, locomotor activity, cisterna magna pressure, and acetylcholine levels in the CSF were monitored. Compared with the 10 d-0 μL group, the escape latency by Morris water maze was significantly prolonged in the 10 d-100 μL and 10 d-150 μL groups (P<0.05). Compared with the 15 d-0 μL group, the indices of 15 d-100 μL and 15 d-150 μL groups had no significant differences. When compared with that at the first training, the exception of the 10 d-150 μL and 15 d-150 μL groups, significant differences in escape latency were found at the 6th attempt (P<0.05). Compared with baseline readings for each group, the cisterna magna pressure in the 10 d-150 μL group began to decrease significantly from the third measurement (P<0.05). The optimal time interval during four CSF collections (100 μL per collection) via cisterna magna percutaneous puncture was determined to be 15 days. The procedure did not significantly affect learning processes, performance, or other related indices.

Neuroprotection of the Developing Brain by Dexmedetomidine Is Mediated by Attenuating Single Propofol-induced Hippocampal Apoptosis and Synaptic Plasticity Deficits.

Dexmedetomidine (DEX) has neuroprotective effects and its efficacy was determined in propofol-treated pups. Postnatal day (P) 7 rats were exposed to propofol and DEX to investigate the induced apoptosis-related gene expression. Furthermore, synaptic structural changes at the cellular level were observed by electron microscopy. Induction of hippocampal long-term potentiation (LTP) of P30 rats and long-lasting performance of spatial discrimination at P30 and P60 were evaluated. After a single propofol exposure to P7 rats, DEX pretreatment effectively rescued the profound apoptosis seen in hippocampal neurocytes, and strongly reversed the aberrant expression levels of Bcl2-like 1 (BCL2L1), matrix metallopeptidase 9 (MMP-9) and cleaved caspase 3 (CC3), and sharply enhanced synaptic plasticity. However, there were no significant differences in escape latency or crossing times in a probe test. This was accompanied by no obvious reduction in search strategies among the rat groups. No impairment of long-term learning and memory in P30 or P60 rats was detected when using a single dose propofol treatment during the most vulnerable period of brain development. DEX was shown to ameliorate the rodent developmental neurotoxicity caused by a single neonatal propofol challenge, by altering MMP-9, BCL2L1 and CC3 apoptotic signaling.

Effects of acorus tatarinowii Schott and alpha asarone on free radicals and nNOS/NO in hippocampus of rats with fatigue movement

To study the effects of acorus tatarinowii Schott and its active ingredient-alpha-asarone on learning and memory, free radical metabolism and nNOS/NO signal in hippocampus of rats with fatigue movement. Eighty SD male rats were randomly divided into eight groups: control group(A), exercise group(B), exercise + alpha-asarone low, middle and high dose treatment group (C, D, E), exercise + acorus tatarinowii Schott low, middle and high dose treatment group (F, G, H),with ten rats in each group. The rats in group C, D and E were administered with alpha-asarone at the doses of 0.10, 0.50 and 1.00 mg.kg-1.WT-1 by ig. The rats in group F, G and H were administered with the extracts of Acorus tatarinowii Schott of at the doses of 0.12, 1.20 and 4.80 g.kg-1.WT-1 by ig. Learning and memory of rats were tested by the method of water maze experiment, and the activities of SOD and NOS, the contents of MDA were detected by the biochemical methods, and the expression levels of nNOS protein in hippocampus of rats were tested by the method of Western blot in at the end of the experiment. The escape latency and MDA content in hippocampus of rats in groups E and H were lower than those in groups B, C, D, F and G and the numbers of Plateau crossing, SOD and NOS activities and the expression levels of nNOS protein in hippocampus of rats were higher than those in groups B, C, D, F and G(P＜0.01). The activities of SOD in hippocampus of rats in groups A, E and H were A＞E＞H, whereas the contents of MDA were opposite (P＜0.01); the activities of NOS and the expression levels of nNOS protein in hippocampus of group E were lower than those of groups A and H (P＜0.01 or P＜0.05), but there was no significant difference between groups A and H (P＞0.05). There were no significant difference in escape latency and numbers of crossing platform among groups A, E and H (P＞0.05). Acorus tatarinowii Schott and alpha-asarone can significantly improve learning and memory of rats with fatigue movement. The mechanism is related to reclaiming the imbalance of free radical metabolism and up-regulating nNOS/NO signal in hippocampus of the rats.

Effect of electroacupuncture on the P35/P25-cyclin-dependent kinase 5-Tau pathway in hippocampus of rats with Alzheimer's disease

To investigate the effect of electroacupuncture on the P35/P25-cyclin-dependent kinase 5 (CDK5)-Tau pathway in rats with Alzheimer's disease (AD), as well as the mechanism of electroacupuncture in the prevention and treatment of AD. Sprague-Dawley rats were randomly divided into control group, sham-operation group, model group, and electroacupuncture treatment group, with 12 rats in each group. A rat model of AD was established by injection of Aβ25-35 into the bilateral hippocampus. The rats in the electroacupuncture treatment group were given electroacupuncture at "Baihui" (GV20) and "Shenshu" (BL23) once a day, 15 min each time, for 10 days. Morris water maze was used to evaluate learning and memory abilities, immunohistochemistry was used to measure the distribution and expression of P35/P25, CDK5, and Tau5 in the hippocampus, and Western blot was used to measure the expression of the above mentioned proteins, phosphory-lated Tau(Ser199, Ser202). In the visual platform test, there were no significant differences in escape latency and search path between groups (P>0.05). In the hidden platform test, there were no significant differences in escape latency and search path between the control group and the sham-operation group (P>0.05); the model group had significantly longer escape latency and search path than the control group and the sham-operation group (P<0.05). Compared with the model group, the electroacupuncture treatment group had significantly shorter escape latency and search path (P<0.05). In the spatial exploration test, there was no significant difference in the number of platform crossings between the control group and the sham-operation group (P<0.05). The model group had a significantly lower number of platform crossings than the control group and the sham-operation group (P<0.01, P<0.05). The electroacupuncture treatment group had a significantly higher number of platform crossings than the model group (P<0.05). Compared with the control group and the sham-operation group, the model group had significant increases in the protein expression of P35/P25 and CDK5 (P<0.001), and the electroacupuncture treatment group had significant reductions compared with the model group (P<0.001). There was no significant difference in the protein expression of Tau5 between groups (P>0.05). The model group had significantly higher protein expression of phosphorylated Tau(Ser199, Ser202) in the hippocampus than the control group and the sham-operation group (P<0.01, P<0.05). The electroacupuncture treatment group had significantly lower protein expression of phosphorylated Tau(Ser199，Ser202) than the model group (P<0.05, P<0.01). Electroacupuncture may delay the progression of AD by affecting the expression of proteins involved in the P35/P25-CDK5-Tau pathway in the hippocampus of rats.

DBcAMP Rescues the Neurons From Degeneration in Kainic Acid-Injured Hippocampus, Enhances Neurogenesis, Learning, and Memory.

Dibutyryl cyclic adenosine monophosphate (dBcAMP) is a cell-permeable synthetic analog of cyclic adenosine monophosphate (cAMP). Although the elevation of cAMP levels was reported to promote the functional recovery in spinal cord injury, its role in neurogenesis or functional recovery after hippocampal injury is unknown. The objective of the study was to investigate the effects of dBcAMP on learning, memory, and hippocampal neurogenesis in the excitotoxically lesioned hippocampus. An excitotoxic lesion was induced in the hippocampi of 4-month-old male BALB/c mice by injecting 0.25 μg/μl into the lateral ventricles of both sides. The lesioned mice (L) were divided into L+dBcAMP and L+phosphate-buffered saline (PBS) groups. Sham surgery (S) was done by the injection of 1 μl of sterile saline into the lateral ventricles. The sham surgery mice were divided into S+dBcAMP and S+PBS groups. Mice in the L+dBcAMP and S+dBcAMP groups were treated with dBcAMP for 1 week (i.p., 50 mg/kg), whereas mice in the L+PBS and S+PBS groups were treated with PBS. The mice in all groups were subjected to water maze and passive avoidance tests at the end of the 4th week. Cresyl violet staining and NeuN and doublecortin immunostaining were done to analyze the morphology and neurogenesis. The water maze learning sessions did not show a significant difference in escape latency between the groups, suggesting an unimpaired learning ability of mice in all groups. The L+dBcAMP mice had significantly short entry latency and higher target quadrant time/distance traveled compared to the L+PBS group, suggesting better memory retention. The L+dBcAMP group had a significantly improved memory retention compared to the L+PBS mice during the passive avoidance test. Morphological studies showed significantly greater adult neurons and increased hippocampal neurogenesis in the hippocampus of mice in the L+dBcAMP group compared to those in the L+PBS group. There was no significant difference between the S+dBcAMP and S+PBS groups in the water maze/passive avoidance tests and the number of neurons. In conclusion, dBcAMP protects the hippocampal neuron from degeneration and enhances hippocampal neurogenesis, learning, and memory.

An unexpected improvement in spatial learning and memory ability in alpha-synuclein A53T transgenic mice.

Growing evidence suggests, as Parkinson's disease (PD) progresses, that its non-motor symptoms appear prior to or in parallel with its motor deficits. Alpha-synuclein A53T transgenic mouse (A53T) is an essential tool to investigate the onsets and the extents of PD non-motor symptoms. Our aim is to investigate spatial learning and memory ability in A53T mice. In our rotarod tests, no motor coordination impairments were detected in mice of 3, 6, 9, and 12 months old. We then investigated their spatial learning and memory ability through Morris water maze in 3- and 9-month-old mice. No significant difference in escape latency was detected among the A53T mice and the control mice. However, an unexpected improvement in spatial learning and memory ability was observed in the probe session among the A53T mice. Reversal learning by Morris water maze also indicated that 3- and 9-month-old A53T mice exhibited a better cognitive flexibility compared to their littermate controls. Further studies by western blots showed that alpha-synuclein expressions in hippocampus of the A53T mice were noticeably up-regulated. The immunofluorescence staining of 5-bromo-2-deoxyuridine (Brdu) and doublecortin (DCX) demonstrated that neither the Brdu-positive neurons nor the Brdu/DCX positive neurons in hippocampus were significantly altered between the two groups. These results suggest that our A53T mice exhibit improved spatial learning and memory ability prior to their motor coordination deficits. These results are not induced by neurogenesis in the hippocampus.

The prophylactic and therapeutic effects of montelukast on delayed neuropsychologic sequelae after acute carbon monoxide poisoning in rat model

Objective o investigate the prophylactic and therapeutic effects of montelukast, a cysteinyl leukotriene receptor-1 (CysLT1R) antagonist, on the delayed neuropsychological sequelae (DNS) in rat model of carbon monoxide (CO) poisoning and to explore the possible underlying mechanism. Methods A total of 90 rats were acclimated for one week prior to screening rat by Morris water maze test. Ten rats were randomly assigned to control group (Con group), and the remaining 80 rats were subjected to modified method of intraperitoneal injection of CO gas to establish animal model of acute CO poisoning, Thereafter, the survival rats randomized into CO poisoning group (Mod group), low-dose montelukast group (ML group), medium-dose montelukast group (MM group), high-dose montelukast group (MH group) (n=10 each). Montelukast was accordingly administered via intragastric tube at different intervals (30 min, 4 h and 12 h) after CO poisoning, and then montelukast was administered every 12 hours for 7 consecutive days. The rats of control group and Mod group received equal volume of normal saline instead at given intervals. Twenty-one days after CO exposure, the average escape latency was measured by Morris water maze test to screen DNS rats followed by H-E staining to observe the pathological changes of cortex and hippocampal CA1 region and TUNEL was used to assess the apoptosis of neurons in cortex and hippocampal CA1 region after rats sacrificed. Results All CO-exposed rats exhibited cognition function lowered, and the escape latency (seconds) in Mod group (43.3 ± 15.5), ML group (31.5 ± 13.2) and MH groups (30.1 ± 12.2) was significantly prolonged compared with Con group (12.1 ± 3.0) (P 0.05). Compared with Mod group, the escape latency in montelukast treatment groups was shortened, whereas the significant difference in escape latency only found between Mod group and MM group (P < 0.05). Except for Con group, DNS was evident in CO-exposed groups, and the numbers of DNS rats in Mod, ML, MM and MH groups were 8, 5, 1, 4, respectively, which made statistically significant differences to Con group (P< 0.05) except MM group. The DNS incidence in MM group was lower than that in Mod group (P < 0.05). Mod group exhibited severe histopathological injury to the brain, with evident apoptosis of neural cells, whereas in the groups with montelukast treatment, histopathological damage to the brain was mitigated and the number of apoptotic neuronal cells was diminished noticeably in MM group. Conclusion Montelukast can ameliorate the cognitive function of rats, decrease the incidence of DNS and reduce the apoptosis of neural cells as well as attenuate neuronal cell injury, thus exerting neuroprotection against DNS in rats with CO poisoning. Key words: Montelukast; Cysteinyl leukotriene receptor-1; Rat; Carbon monoxide poisoning; Delayed neuropsychologic sequelae; Morris water maze; Escape latency; Neuronal apoptosis

Nerve growth factor injections administered intranasally combined with exercise can improve learning and memory

Objective To investigate the effect of nerve growth factor (NGF) combined with exercise training on nerve protection, learning and memory. Methods Twenty-four six-month-old APP/PS1 mice were randomly divided into a control group, an NGF group, an exercise group and an NGF combined with exercise training group (the combined group), each of 6. The control group mice were given 50 μL of saline intra-nasally every day, while the NGF group were given 50 μL of NGF solution (0.1 mg/ml) intranasally. The exercise group was given 50 μL of saline intra-nasally plus 30 minutes of treadmill exercise daily, while the combined group was given 50 μL of the NGF solution and 30 minutes of exercise. The intervention lasted 21 days. Then Morris water maze test was conducted to evaluate the memory of all groups, and all of the mice were sacrificed and immunohistochemical staining was used to check the levels of APP, Ki-67 expression in cortex and NeuN expression in hippocampus. Results In the place navigation test, significant differences in escape latency were observed among the 4 groups, with the NGF, exercise and combined groups showing average latencies significantly shorter than that of the control group The average latency of the combined group was also significantly shorter than that of the NGF and exercise groups. In the spatial probe, there were significant differences among the 4 groups in the percentage of time spent in the target quadrant. The combined group′s average was significantly larger than those of the NGF and exercises groups. The immunochemistry showed that the combined group had better-arranged neurons and more cells compared with the 3 other groups. The average APP protein expression of the combined group was significantly lower than that of the other groups, but their Ki-67-positive and NeuN-positive cells were found to be significantly more numerous. Conclusion NGF combined with exercise can improve learning and memory, at least in APP/ PS1 mice. This might be associated with its reducing the expression of APP and promoting the expression of Ki-67 and NeuN. Key words: Alzheimer′s disease; Nerve growth factors; Exercise; Learning ability; Memory

BACE1 in the retina: a sensitive biomarker for monitoring early pathological changes in Alzheimer's disease.

Because of a lack of sensitive biomarkers, the diagnosis of Alzheimer's disease (AD) cannot be made prior to symptom manifestation. Therefore, it is crucial to identify novel biomarkers for the presymptomatic diagnosis of AD. While brain lesions are a major feature of AD, retinal pathological changes also occur in patients. In this study, we investigated the temporal changes in β-site APP-cleaving enzyme 1 (BACE1) expression in the retina and brain to determine whether it could serve as a suitable biomarker for early monitoring of AD. APP/PS-1 transgenic mice, 3, 6 and 8 months of age, were used as an experimental group, and age-matched C57/BL6 wild-type mice served as the control group. In the Morris water maze test, there were no significant differences in escape latency or in the number of crossings in the target area among mice of different ages. Compared with wild-type mice, no changes in learning or memory abilities were detected in transgenic mice at 3 months of age. However, compared with wild-type mice, the escape latency was significantly increased in transgenic mice at 6 months, starting on day 3, and at 8 months, starting on day 2, during Morris water maze training. In addition, the number of crossings of the target area was significantly decreased in transgenic mice. The learning and memory abilities of transgenic mice were further worsened at 8 months of age. Immunohistochemical staining revealed no BACE1 plaques in wild-type mice at 3, 6 or 8 months or in transgenic mice at 3 months, but they were clearly found in the entorhinal cortex, hippocampus and prefrontal cortex of transgenic mice at 6 and 8 months. BACE1 expression was not detected in the retina of wild-type mice at 3 months, but weak BACE1 expression was detected in the ganglion cell layer, inner plexiform layer and outer plexiform layer at 6 and 8 months. In transgenic mice, BACE1 expression in the ganglion cell layer was increased at 3 months, and BACE1 expression in the ganglion cell layer, inner plexiform layer and outer plexiform layer was significantly increased at 6 and 8 months, compared with age-matched wild-type mice. Taken together, these results indicate that changes in BACE1 expression appear earlier in the retina than in the brain and precede behavioral deficits. Our findings suggest that abnormal expression of BACE1 in the retina is an early pathological change in APP/PS-1 transgenic mice, and that BACE1 might have potential as a biomarker for the early diagnosis of AD in humans.

Electroacupuncture Ameliorates Cognitive Impairment and Regulates the Expression of Apoptosis-Related Genes Bcl-2 and Bax in rats with cerebral ischaemia-reperfusion injury

Post-stroke cognitive impairment seriously affects the quality of life and functional rehabilitation of patients with stroke. To examine the effects of electroacupuncture (EA) at GV20 and GV24 on cognitive impairment and apoptosis including expression of apoptosis-related genes Bcl-2 and Bax in a rat model of cerebral ischaemia-reperfusion (IR) induced by middle cerebral artery occlusion (MCAO). Thirty-five Sprague-Dawley rats were allocated to a sham operation control group (SC group, n=10) or underwent surgery and MCAO (n=25). Postoperatively the latter group was randomly subdivided into EA or untreated (IR) groups. Cognitive impairment was assessed using the Morris water maze (MWM). Apoptosis was examined by detection of Bcl-2 and Bax expression in the cerebral cortex. The EA group had significantly decreased neurological deficit scores compared to the IR group (p<0.05). In the MWM test, significant differences in escape latency and route were observed between the EA and IR groups (p<0.05). Rats in the EA group performed better in the probe trial than those in the IR group (p<0.05). EA treatment markedly reduced the number of TUNEL-positive cells compared to the IR group (20.13±4.30% vs 38.40±3.38%; p<0.001). Reverse transcription-polymerase chain reaction (RT-PCR) results showed the Bcl-2/Bax ratio was significantly increased in the EA group compared to the IR group (1.61±0.19 vs 0.50±0.05, p<0.01). These findings suggest that EA ameliorates cognitive impairment of rats with IR injury by modulating Bcl-2 and Bax expression.

Zinc deficiency with reduced mastication impairs spatial memory in young adult mice

Sufficient oral microelements such as zinc and fully chewing of foods are required to maintain cognitive function despite aging. No knowledge exists about the combination of factors such as zinc deficiency and reduced mastication on learning and memory. Here we show that tooth extraction only in 8-week-old mice did not change the density of glial fibrillary acidic protein-labeled astrocytes in the hippocampus or spatial memory parameters. However, tooth extraction followed by zinc deprivation strongly impaired spatial memory and led to an increase in astrocytic density in the hippocampal CA1 region. The impaired spatial performance in the zinc-deficient only (ZD) mice also coincided well with the increase in the astrocytic density in the hippocampal CA1 region. After switching both zinc-deficient groups to a normal diet with sufficient zinc, spatial memory recovered, and more time was spent in the quadrant with the goal in the probe test in the mice with tooth extraction followed by zinc deprivation (EZD) compared to the ZD mice. Interestingly, we found no differences in astrocytic density in the CA1 region among all groups at 22weeks of age. Furthermore, the escape latency in a visible probe test at all times was longer in zinc-deficient groups than the others and demonstrated a negative correlation with body weight. No significant differences in escape latency were observed in the visible probe test among the ZD, EZD, and normal-fed control at 4weeks (CT4w) groups in which body weight was standardized to that of the EZD group, or in the daily reduction in latency between the normal-fed control and CT4w groups. Our data showed that zinc-deficient feeding during a young age impairs spatial memory performance and leads to an increase in astrocytic density in the hippocampal CA1 region and that zinc-sufficient feeding is followed by recovery of the impaired spatial memory along with changes in astrocytic density. The combination of the two factors, zinc deficiency and reduced mastication, but not body weight, may inhibit recovery of impaired spatial learning. A zinc-sufficient diet is pivotal for maintaining spatial memory.

Effect of Postnatal Chronic Lead Exposure on Spatial Learning and Memory in Male Rat

Objectives: The aim of present study was to evaluate the effects of neonatal lead exposure on spatial learning and memory in Morris water maze. Materials and Methods: In this experimental study, 30 new born male rats were randomly divided into two groups: Control and lead exposure groups. Rat pups in lead exposure group received 8 mg/kg lead acetate intraperitoneally daily for 21 days. Then, rats trained with 6 trials per day for 6 consecutive days in the water maze at 36th postnatal day (PD). Twenty four hours after ending of training, a probe test was done to measure memory retention. Results: Results of this study demonstrated that exposure to lead could affect learning as indicating by significant differences in escape latency and traveled distance between 2 groups during 6 days of training. Lead exposure group exhibited significantly higher escape latency and distance traveled during training trials compared to control group. Also, lead exposure rats had higher platform location latency than control group during probe trial (P < 0.05). Conclusions: These data suggests that lead exposure during early postnatal period of brain development causes impairment in spatial learning and memory.

Effects of enriched environment and impoverished environment on learning and memory ability of manganese-exposed mice

To investigate the effects of enriched environment and impoverished environment on the learning and memory ability of manganese-exposed mice and the mechanism. Forty female Kunming mice were randomly and equally divided into 4 group: control group (CG), standard environment and manganese exposure group (SEG), enriched environment and manganese exposure group (EEG), and impoverished environment and manganese exposure group (IEG). The mouse model of manganese poisoning was established by intraperitoneal injection of manganese chloride. The learning and memory ability was tested by Morris water maze. The expression of cAMP response element-binding protein (CREB) in area CA1 of the hippocampus was measured by immunohistochemistry. In place navigation test, the SEG had a significantly longer escape latency than the CG (P < 0.05), and the EEG had a significantly shorter escape latency than the SEG (P < 0.05); there was no significant difference in escape latency between IEG and SEG (P > 0.05). In spatial probe test, the EEG had a significantly greater number of platform crossings than the SEG (P < 0.05), and the IEG had a significantly smaller number of platform crossings than the SEG (P < 0.05). The expression of CREB in area CA1 of the hippocampus was significantly lower in IEG and SEG than in CG (P < 0.05), and it was significantly higher in EEG than in SEG (P < 0.05). In the enriched environment, the learning and memory ability of manganese-exposed mice can be improved, which may be due to the increased expression of CREB in the hippocampus.

Effect of propofol on ketamine-induced cognitive dysfunction in aged rats

Objective To investigate the effect of propofol on ketamine-induced cognitive dysfunction and neuronal apoptosis in hippocampus in aged rats. Methods Thirty-two male SD rats aged 18-24 months weighing 380-470 g were randomly divided into 4 groups ( n = 8 each) :control group (group C);propofol group (group P);ketamine group (group K) and propofol + ketamine group (group PK). Propofol 30 mg·kg-1·h-1 or/and ketamine 40 mg· kg-1·h-1 were infused for 2 h once a day for 7 consecutive days. After the last day of drug administration cognitive function was assessed using Morris water maze (escape latency and the number of animals' swimming across the platform). The animals were sncrificed after water naze test and their hippocampi were removed for determination of neuronal apoptosis (by TUNEL) and caspase-3 expression (by immuno-histochemistry) in hippocampal CA1 region. Results There was no significant difference in escape latency and the number of the animals,swimming across the platform, the neuronal apoptotic rate (the number of apoptotic neurons/the number of total neurons) and caspase-3 expression between group C and P. In group K and PK the escape latency was prolonged,the number of animals' swimming across the platform was decreased, neuronal apoptotic rate increased and the caspase-3 expression up-regulated as compared with group C. The ketamine-induced changes were significantly attenuated by coadministration of propofol in group PK. Conclusion Coadministration of propofol can ameliorate ketamine-induced cognitive dysfunction and hippocampal neuronal apoptosis. Key words: Propofol; Ketamine; Cognition disorders; Aged

Effect of Mastication on Functional Recoveries after Permanent Middle Cerebral Artery Occlusion in Rats

We evaluated whether solid feed is more effective for functional recoveries than liquid feed in rats with ischemic brain injury after permanent middle cerebral artery occlusion (MCAO). A total of 36 male Wistar/ST rats were subjected to MCAO or sham surgery. After MCAO or sham surgery, all rats were provided liquid feed for 14 days. Then, all rats were divided into 3 groups: the solid feeding group, the liquid feeding group, and the solid feeding group of sham. Effect of mastication on functional recoveries after permanent MCAO in rats was evaluated by the limb placement test and Morris water maze (MWM) task. After surgery, limb placement test scores were equal in both MCAO groups. In the acquisition trials of MWM task, statistically significant differences in escape latency were observed between the liquid feeding group and sham groups at all days, and between the solid feeding group and sham groups at days 3 and 4 of the trials. In the probe trial, statistically significant differences in time spent were observed between the liquid feeding group and sham group. On day 5 of acquisition trials, the time spent in the periphery of the pool in MWM task was significantly different among the 3 groups. This study suggested that solid diet mastication could be effective for the rehabilitation of sensorimotor and learning/memory dysfunction induced by cerebral infarction.

Effect of isoflurane on synaptophysin expression in hippocampal CA3 area in aged rats

Objective To investigate the effect of isoflurane on the synaptophysin expression in hippocampal CA3 area in aged rats. Methods Sixty-three 24-month-old SD rots, weighing 400-650 g, were randomly divided into 3 groups (n=21 each): control group (group C), 1.2% isoflurane group (group E_1), and 1.8% isoflurane group (group E_2). The rats in group C only inhaled a gas mixture containing 40% oxygen for 3 h. The rats in group E_1 and E_2 inhaled 3% isoflurane for induction, and after righting reflex disappeared, the concentration was reduced to 1.2% and 1.8% respectively which was maintained for 3 h. Twelve rats randomly selected from each group underwent Morris water maze teat for assessment of learning and memory function (escape latency and probe time). The training test was performed 4 times a day for 7 d. Nine rats randomly selected from each group were decapitated at day 1,3, and 7 after the termination of anesthesia. The hippocampal CA3 area was isolated for determination of synaptophysin expression. Results The escape latency was significantly longer at day 2 and 3 after the termination of anesthesia in group E_1 and E_2 than in group C (P 0.05). The synaptophysin expression in hippocampal CA3 area was significantly lower in group E_1 and E_2 than in group C (P 0.05). There was no significant difference in escape latency between group E_2 and group E_1 (P > 0.05), and the synaptophysin expression in hippocampal CA3 area was significantly lower in group E_2 than in group E_1 (P < 0.01). Conclusion The cognitive dysfunction induced by isoflurane anesthesia in aged rats is not related to the synaptophysin expression in hippocampal CA3 area. Key words: Isoflurane; Synaptophysin; Cognition disorders; Aged

The Effect of Severe Zinc Deficiency and Zinc Supplement on Spatial Learning and Memory

Zinc deficiency during pregnancy and during lactation has been shown to impair cognitive function and motor activity in offspring rats. In the present study, the effect of zinc deficiency and zinc supplement on spatial learning and memory in Morris Water Maze (MWM) and motor activity in open field were investigated. Pregnant rats after mating were divided to three groups. Control group fed a standard diet and a zinc deficient (ZnD) group fed a diet deficient in zinc (0.5-1.5 ppm) and a zinc supplement (ZnS) group fed a standard diet and enhanced zinc in the drinking water (10 ppm). All the diets were exposed during the last trisemester of pregnancy and during lactation. Rat's offspring in these groups were tested for spatial learning and memory in MWM at post natal day (PND) 56 and were tested for motor activity in open field at PND 66.The Escape Latency (EL) and Traveled Distance (TD) in the ZnD group were increased but Percentage of Time Spent in the target quadrant (PTS) was decreased compared to the control group. In addition, these were no significant differences in EL and TD, but PTS had significant increase in ZnS compared to the control group. In the open field, Total Distance Moved (TDM) and Time of Motor Activity (TMA) for the ZnD were decreased compared to the control group, but there were no significant differences in TDM and TMA between control and ZnS groups. These findings suggest that zinc deficiency during the last trimester of pregnancy and during lactation impaired spatial learning and memory in their offsprings and has also negative effect on motor activity. In addition, ZnS has a significant effect on spatial learning and memory but no effect on motor activity in their offsprings.

Effect of Lead (Pb2+) Exposure in Female Pregnant Rats and Their Offspring on Spatial Learning and Memory in Morris Water Maze

Lead (Pb 2+ ) is a well known neurotoxin that was frequently found in the environment and chronic exposure to lead has been matter of public health. In the present study the effect of lead on spatial memory in developmentally exposed rats and their dams in Morris water maze task were investigated. Female rats were divided into three groups and two groups exposed to 250 and 750 part per million (ppm) Pb acetate and one group Na acetate , as a control group, through drinking water, ten days prior to mating and continue through pregnancy, pregnant animals were tested in the swim task at gestation day 14±2. Another group of animals exposed to the same concentration of Pb acetate at different developmental stages including a maternally exposed group (including gestation and lactation period) and continuously exposed group (including gestation, lactation and continue to lead exposure until test time). Rats in these groups were tested for spatial learning and memory in Morris water maze task at post natal day (PND) 56. Exposure to lead did not affect learning ability of dams in Morris water maze performance indicating by no significant differences in escape latency and traveled distance between groups, but, for both maternally-and continuously-exposed groups treated with 750 ppm lead, average escape latency and traveled distance were increased, indicating significant impairment in spatial learning and memory. These results are more direct evidence that indicate developing brain is more susceptible to Pb 2+ induced neurotoxicity.

Prenatal protein malnutrition affects avoidance but not escape behavior in the elevated T-maze test

An elevated T-maze was used to study the effects of prenatal protein deficiency on inhibitory avoidance and escape behaviors. Female rats were provided with a 25% (control) or a 6% (low protein) casein diets before and during pregnancy. After birth, eight pups in each litter (six males and two females) were fostered to a lactating well-nourished mother. After weaning (21 days of age) all animals received a lab chow diet. Behavioral testing of these offspring began at 70 days of age. To assess inhibitory avoidance, prenatally malnourished and control rats were placed individually at the end of an enclosed arm in an elevated T-maze (one enclosed and two open arms) and the time taken to emerge from this arm was recorded. The same procedure was repeated in 2 subsequent trials given at 30-s intervals. Thirty seconds after the last of these trials, the rat was placed at the end of one open arm and the time taken to withdraw from this arm was measured, thus estimating escape latency. To assess retention, inhibitory avoidance and escape were measured again 72 h later. Prenatally malnourished males and females did not significantly increase avoidance latency from trials 1–3, in contrast to male and female controls. Only control female rats significantly reduced their avoidance latency on the retention test. No significant differences in escape latency were found between diet groups. These results suggest that prenatal malnutrition results in a reduction of anxiety, and that there are gender-specific responses to this test.