Subject(s)
Anxiety/metabolism , Carrier Proteins/metabolism , Animals , Body Weight/physiology , Brain/anatomy & histology , Brain/metabolism , Carrier Proteins/genetics , Exploratory Behavior/physiology , Female , Intracellular Signaling Peptides and Proteins , Memory/physiology , Mice, 129 Strain , Mice, Inbred C57BL , Mice, Knockout , Motor Activity/physiology , Psychological TestsABSTRACT
As an important neurotransmitter, adenosine displays its functions by acting on the adenosine receptors. Recent studies have shown that the distribution, expression and balance among subtypes of adenosine receptors are closely related with cognitive activities, and changes of adenosine receptors play key roles in neurodegenerative disorders including Alzheimer's disease. It has been pointed out that prolonged activation of adenosine receptors by high level adenosine may lead to the disturbance of balance among adenosine receptor subtypes. This imbalance mainly performed as increased expression of A2a receptor and decreased expression of A1 receptor, and enhancement of the excitatory signals mediated by A2a receptor and weakened inhibitory signals mediated by A1 receptor. Changes of these two subtypes of adenosine receptors may lead to a lot of disorders of neurological activities which developed into dysfunction of cognition to the end. These findings imply that the potential of maintaining the balance among adenosine receptors on the treatment of AD would facilitate both the revealing of the mechanism and the cure of AD.
Subject(s)
Adenosine/physiology , Alzheimer Disease/physiopathology , Receptors, Purinergic P1/physiology , Humans , Neurotransmitter Agents/physiology , Receptors, Purinergic P1/classificationABSTRACT
Previous studies showed that Danggui-Shaoyao-San (DSS), a traditional Chinese medicinal prescription, could alleviate cognitive dysfunction of Alzheimer's disease (AD) patients. However, the mechanisms remain unclear; we have now examined the effect of DSS on SAMP8 and elucidated the possible mechanism. Animals were treated with DSS for 2 months, and step-down test and Morris water maze (MWM) test were used to evaluated cognitive abilities. The estradiol (E2), NO, and glycine in blood plasma or in hippocampus were detected to explore the possible mechanisms. The latency of SAMP8 in step-down test was shorter than that of age-matched SAMR1, and DSS increased the latency especially in female animals. In MWM test, we got similar results; SAMP8 spent more time to find the platform, and DSS decreased the time before finding the platform, with little effect on swim velocity, during the training sessions. During test session, DSS increased the time spent in target quadrant especially in female SAMP8. In female SAMP8, plasma E2, NO, and glycine were elevated in plasma or hippocampus tissue. In conclusion, DSS could ameliorate deterioration of cognition in SAMP8, especially in female animals. Increasing E2, NO, and glycine might contribute to the cognitive improvement effect of DSS in female SAMP8.
Subject(s)
Brain/metabolism , Electroporation/methods , Gene Transfer Techniques , Green Fluorescent Proteins/genetics , Nerve Tissue Proteins/genetics , Neuroglia/metabolism , Animals , Glial Fibrillary Acidic Protein , Green Fluorescent Proteins/metabolism , HEK293 Cells , Humans , Injections, Intraventricular , Lateral Ventricles , Mice , Microscopy, Fluorescence , Nerve Tissue Proteins/metabolism , Nestin/genetics , Nestin/metabolism , Promoter Regions, GeneticABSTRACT
Paeoniflorin (PF) is the chief active component of paeonia, with diverse pharmacological actions and wide application. Recently, the effect of PF on nervous system has attracted increasingly more attention. According to current study findings, PF can ameliorate the decline of memory and learning capacities in many dementia model animals, and have effect in protecting the cerebral ischemia injury, treating Parkinson's disease, reliving pain and improving neural synapse plasticity. Thought its mechanism has not been clarified, current findings show that adenosine A1 receptor plays an important role, while M cholinergic receptor, opiate receptor, calcium ion channel and NF-KB may also play a part in paeoniflorin's effect on nervous system.
Subject(s)
Benzoates/pharmacology , Bridged-Ring Compounds/pharmacology , Glucosides/pharmacology , Nervous System/drug effects , Animals , Calcium Channels/metabolism , Learning/drug effects , Memory/drug effects , Monoterpenes , NF-kappa B/metabolism , Nervous System/metabolism , Receptor, Adenosine A1/metabolismABSTRACT
In vivo electroporation works as an effective method to transfer exogenous genes into postnatal rodent forebrain. Nevertheless, two deficiencies were found in the reported methods. First, surgical operation brings unnecessary trauma to newborn pups. Second, the procedure was complicated and the transfection efficiency was relatively low. Here we improved the previous electroporation method and make it more simple and efficient. The pulse voltage was decreased to 90 v. DNA injection into one pup's forebrain could be completed within 30 s without any surgical operation. More than 94% of injected neonates survived. Almost 100% of the survivors expressed the introduced gene and the expression persists as long as 20 days after injection. Thus, this method offers a powerful new way for gene function study in postnatal neurogenesis and neural development.
Subject(s)
Brain/metabolism , Electroporation , Gene Transfer Techniques , Animals , Animals, Newborn , Mice , Mice, Inbred ICRABSTRACT
The hippocampus has important roles in learning and memory. Many in vivo experiments require accurate location of a certain region of the hippocampus, long-term potentiation (LTP) recording being one of them. In vitro and in vivo studies can be used to measure LTP in the hippocampus. It is more difficult in vivo to locate the specific brain region than in vitro. Location of the dentate gyrus (DG) and perforant path (PP) is usually achieved using brain stereotaxic atlasses. Because the data in the atlasses were obtained from a particular rat/mouse strain (Rat: adult Wistar, 290 g; Mouse: adult C57BL/J6, 26-30 g), the data in atlases could not be easily applied in all the different other strains of these species. We describe a method that uses landmarks on the skull to locate these structures in both species, which has been successfully applied in BALB/c mice, KM mice, SAMP8, SAMR1 and Wistar rats; making it a reliable and useful means of locating the DG and PP.
Subject(s)
Dentate Gyrus/anatomy & histology , Perforant Pathway/anatomy & histology , Skull/anatomy & histology , Aging/genetics , Animals , Electrodes , Male , Mice , Mice, Inbred Strains , Rats , Rats, Mutant Strains , Rats, WistarABSTRACT
JD-30 is an active fraction extracted from Danggui-Shaoyao-San (DSS), a traditional Chinese medicinal prescription. We previously showed that JD-30 could alleviate cognitive dysfunction of the mice induced by intracerebroventricular injection of ß-amyloid (Aß). However, data remain scarce on the effect of JD-30 on an Alzheimer's disease (AD) model and the underlying mechanisms are unknown. Further detailed studies on the effects of JD-30 on spatial cognition of senescence-accelerated mouse prone 8 (SAMP8), a suitable rodent model for cognitive impairment of aged subjects were investigated to elucidate the possible mechanisms. Long-term treatment with JD-30 significantly decreased the prolonged latency of SAMP8 in the Morris water-maze test. It also ameliorated the reduction of long-term potentiation (LTP) and reduced the damage of neurons in the hippocampus of SAMP8. Finally, JD-30 decreased the content and deposition of Aß in the brain of SAMP8. The results show that JD-30 improves deterioration of spatial learning and memory in the SAMP8 mouse model, and by decreasing the content and deposition of Aß, neuronal activity and synaptic plasticity improve, suggesting one of the mechanisms involved.
Subject(s)
Alzheimer Disease/prevention & control , Amyloid beta-Peptides/drug effects , Cognition Disorders/prevention & control , Drugs, Chinese Herbal/pharmacology , Long-Term Potentiation/drug effects , Alzheimer Disease/physiopathology , Amyloid beta-Peptides/genetics , Amyloid beta-Peptides/metabolism , Animals , Brain Chemistry/drug effects , Cognition Disorders/physiopathology , Drugs, Chinese Herbal/chemistry , Electrophysiological Phenomena/drug effects , Female , Gene Expression , Hippocampus/drug effects , Male , Maze Learning/drug effects , Memory/drug effects , Mice , Mice, Inbred Strains , Spatial Behavior/drug effectsABSTRACT
AIMS OF THE STUDY: Previous studies showed that Danggui-Shaoyao-San (DSS), a traditional Chinese medicinal prescription, could alleviate cognitive dysfunction of Alzheimer's disease (AD) patients. However, the mechanism and substance basis remain unknown. JD-30 is a fraction extracted from DSS, whose activity we previously was evaluated. beta-Amyloid (Abeta) is believed to be a critical etiological factor of AD. We have now examined the effect of DSS and JD-30 on AD model mice induced by Abeta, and elucidated the possible mechanism. MATERIALS AND METHODS: Mice were intracerebroventricular injected with the aggregated Abeta(25-35) to mimic AD. Groups of mice were treated with DSS or JD-30 by intragastric infusion over 2 weeks, and their spatial learning and memory capacities were measured by the Morris water maze procedure. The mechanisms were investigated by extracellular microelectrode recordings, and also electron microscopy. RESULTS: Our results show that Abeta(25-35) induced impairment of spatial learning and memory in mice, as well as inhibition of long-term potentiation (LTP) in the hippocampus. The impairments were ameliorated by DSS or JD-30 administration. Additionally, JD-30 not only prevented the aggregation of Abeta(25-35), but disrupted aggregated Abeta(25-35) fibrils. CONCLUSION: These results suggest that JD-30 is one of the chief active fractions extracted from DSS by its ability to ameliorate deterioration of cognition, and by blocking and disrupting the aggregation of Abeta so that synaptic plasticity was improved, which may be one of the mechanisms involved.
