ABSTRACT
Objective To investigate the effects of low-fat diet or statin intervention at early age on brain amyloid β-protein (Aβ) pathology and behaviors of middle-aged Tg2576 mice.Methods Thirty-five two-month-old Tg2576 mice were randomly divided into following 5 groups:a juvenile statin group,a juvenile low-fat diet group,a young statin group,a young low-fat group,and a blank control group (n=7);mice in the low-fat diet groups were given standard low-fat feed,and mice in the statin group were given atorvastatin at 17 mg/(kg· d) into the normal diet.The initiation times of intervention were,respectively,set to be 2-month-old in juvenile groups and 6-month-old in young groups;meanwhile,mice in the blank-control group were fed with normal diet without statin.All mice were raised to be 10-month-old and tested by Morris water maze for evaluating cognitive behaviors two weeks before execution.After peripheral blood and brains being taken,a monoclonal anti-Aβ42 antibody was employed to immunostain mice brain paraffin tissue sections for assaying tissue Aβ plaque immunoreactivity (TAPIR),and the levels of Aβ40,Aβ42,β-secretase,and γ-secretase in homogenates were detected by enzyme-linked immunosorbent assays (ELISA).Results As compared with those in the blank-control group,the average escape latencies,times of passing through hidden platforms,percentage of strong TAPIR,Aβ42 and γ-secretase level in all intervention groups showed no statistical differences (P＞0.05).As compared with those in the blank control group,Aβ42 in homogenates of young intervention groups and β-secretase level in the young statin group were significantly higher (P＜0.05).Conclusion Interventions initiated from juvenile or young,and low-fat diet intervention or statin intervention can neither improve the mice's Morris water maze testing results,nor reduce Aβs burdens in brain homogenates and Aβ40 immunopathologies in brain tissues of middle-aged mice;over early initiation of low-fat diet intervention or statin intervention might accelerate or worsen Alzheimer's disease progress.
ABSTRACT
BACKGROUND: Hippocampal structure in brain is the division related to learning and memory, generally it is closely relevant to spatial cognitive activity. Marginal division of striatum is a latest discovered subdivision related to learning and memory function of brain, whether is its learning and memory function different from that in hippocampus?OBJECTIVE: To compare the difference, function and importance in learning and memory function between marginal division of striatum and hippocampus in brain and observe the difference in escape learning and memory between marginal division of striatum and hippocampus.DESIGN: Completely randomized controlled experiment.SETTING: Institute of Neuroscience in Zhujiang Hospital Affiliated to First Military Medical University of Chinese PLA.MATERIALS: The experiment was performed in Institute of Neuroscience in Zhujiang Hospital Affiliated to First Military Medical University of Chinese PLA from March 2002 to July 2003. Totally 109 normal male adult SD rats were employed and 75 rats of them were screened as the qualified animals by twice Y-maze test. Randomly, 25 rats were divided into damaged marginal division of striatum group (DMD group), 10 rats were into bilateral fimbria-fornix transection group (FFT group), 30 rats were into the control of marginal division of striatum (MD control) and 10 rats were into the control of bilateral fimbria-fornix group (FF control). After 24 hours training in Y-maze,In DMD group, 10 g/L kainic acid 0.1 to 0.2 μL was used to damage bilateral marginal division of striatum of rats. In MD control, physiological saline of minim dose was injected in bilateral marginal division of striatum of rats. In FFT group, bilateral fimbria-fornix was transectioned. In FF control, the cortical tissue of the superficial layer of bilateral fimbria-fornix was transectioned. The operation was done on the second day after the 2nd screening. The behavior of rats in learning and memory was observed in Y-maze on the 5th day after operation (during 30 times of maze test, if success frequency ≥ 15,normal capacity of learning and memory was identified.).MAIN OUTCOME MEASURES: Success frequency of rats in different groups in Y-maze learning before and after operation.RESULTS: Of 109 normal male adult SD rats, 75 rats were screened to be qualified after twice Y-maze test. During the experiment, 3 rats were died and other 32 rats fell into disuse for the drug or physiological saline was not injected accurately to the marginal division of striatum. Terminally, 40 rats entered the analysis in total, of which, 11 rats were in DMD group, 9 rats in MD quency in Y-maze learning of rats in DMD group after operation was lower than MD control, FFT group and FF control [(9.27±4.29) times, (22.56±4.25)frequency in Y-maze learning of rats in DMD group after operation was also significantly lower than that before operation [(9.27±4.29) time, (18.27±3.07)FFT group was basically same as FF control and MD control (P=0.660 and P=0.489) and it was basically same to the success frequency in Y-maze learning before operation (P=0.700).CONCLUSION: The learning of Y-maze in rats with damaged marginal division of striatum was remarkably reduced and there was no obvious change in learning and memory between the rats with fimbria-fornix transaction and without transaction. It is verified that marginal division of striatum can reflex complex learning and memory behavior in electric Y-maze test, which cannot be achieved in hippocampus. It is further explained the difference of the two divisions in controlling learning and memory in cerebrum, the marginal division of striatum is able to control hippocampus in learning and memory function.
ABSTRACT
BACKGROUND: The marginal division, a new sub-region in rat brain striatum discovered in recent decades, has been found to closely relate to learning and memory function of the brain. The immediate-early genes such as c-fos and c-jun participate in the signal transduction of learning and memory in the marginal division. But what other intermediate events are initiated in the marginal division in the process of learning and memory?Cyclic adenosine monophosphate (cAMP) response element-binding protein (CREBP) is an molecule essential for the formation of long-term memory,and investigation of the expression and distribution of phosphorylated CREBP in the striatum may help understand the signal transduction mechanism in the striatum during learning and memory at the molecular level.OBJECTIVE: To investigate the expression of phosphorylated CREBP in rat brain stratum during learning and memory process.DESIGN: Completely randomized controlled study.SETTING: Institute of Neurosciences, Zhujiang Hospital of the First Military Medical University of Chinese PLA.MATERIALS: This experiment was conducted in the Institute of Neurosciences, Zhujiang Hospital of the First Military Medical University of Chinese PLA between April and August 2003. Totally 48 normal male adult SD rats were provided from the Experimental Animal Center of First Military Medical University, and after two Y-maze tests, 40 rats were selected for this study (MG-2 type, Sanshengxing electricity company).METHODS: The 40 SD rats were randomized into 4 equal groups. The rats in the first group were subjected to training to acquire dark avoidance reflex in a Y maze, those in the second group underwent sham training with only light stimulation in the Y maze without electricity on the floor.The rats in the third group were trained in the Y maze with electricity on the floor but not light stimulations, with the rest 10 rats serving as the control group subjected to sham training in the Y maze without either electric or light stimulations. After the training in the Y maze, the rats were sacrificed immunohistochemical detection of phosphorylated CREBP expression in the brain striatum.MAIN OUTCOME MEASURES: Expression of phosphorylated CREBPin rat brain striatum.RESULTS: All the 40 rats enrolled in this study were examined for phosphorylated CREBP expression. Positive expression of phosphorylated CREBP was observed in the medial marginal division of the brain striatum after the rats were trained in the Y maze with electric stimulation, but no obvious expression was seen in rats in the sham training or control groups.Massive expression of phosphorylated CREBP could be observed, typically,in the hippocampus, front prefrontal lobe cortex and cingulate gyrus of the rat brain.CONCLUSION: The transcriptional factor phosphorylated CREBP in the marginal division of the striatum participates in the signal transduction for learning and memory in rats receiving Y maze training to acquire dark avoidance reflex.