OBJECTIVE: Exposure to high intensity, low frequency noise (HI-LFN) causes vibroacoustic disease (VAD), with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the memory deficit is unknown. This study aimed to characterize potential mechanisms involving morphological changes of neurons and nerve fibers in the hippocampus, after exposure to HI-LFN. METHODS: Adult wild-type and transient receptor potential vanilloid subtype 4 knockout (TRPV4^-/-) mice were used for construction of the HI-LFN injury model. The new object recognition task and the Morris water maze test were used to measure the memory of these animals. Hemoxylin and eosin and immunofluorescence staining were used to examine morphological changes of the hippocampus after exposure to HI-LFN. RESULTS: The expression of TRPV4 was significantly upregulated in the hippocampus after HI-LFN exposure. Furthermore, memory deficits correlated with lower densities of neurons and neurofilament-positive nerve fibers in the cornu ammonis 1 (CA1) and dentate gyrus (DG) hippocampal areas in wild-type mice. However, TRPV4^-/- mice showed better performance in memory tests and more integrated neurofilament-positive nerve fibers in the CA1 and DG areas after HI-LFN exposure. CONCLUSION TRPV4 up-regulation induced neurofilament positive nerve fiber injury in the hippocampus, which was a possible mechanism for memory impairment and cognitive decline resulting from HI-LFN exposure. Together, these results identified a promising therapeutic target for treating cognitive dysfunction in VAD patients.
Animals ; Mice ; TRPV Cation Channels/metabolism* ; Intermediate Filaments/metabolism* ; Hippocampus/metabolism* ; Neurons/metabolism* ; Memory Disorders/metabolism*

Progress of studies concerning the protective effect of ginsenoside on central nerve system (CNS) in animals and its mechanism published in recent decade were reviewed in this paper. It showed that ginsenosides could improve the learning capacity and memory in normal, aged animals, as well as in model animals with impaired memory. The mechanism of the protective effect on CNS involves the effects on calcium channel blockade, glutamate and gamma-aminobutyric acid, antiperoxidation, estrogen-like action, nitric oxide and its synthase, also the inhibition on cerebral nerve cell apoptosis and amelioration on mitochondrial dysfunction, etc.
Aging ; drug effects ; Animals ; Avoidance Learning ; drug effects ; Ginsenosides ; pharmacology ; Memory ; drug effects ; Memory Disorders ; drug therapy ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Nitric Oxide Synthase ; metabolism

OBJECTIVETo study the mechanism of learning and memory dysfuction in the transgenic mouse expressing human tau 40 isoform with P301L mutation (F10).

METHODSThe human tau protein expression and phosphor-tau protein levels were detected with Western blot method. The neurofibrillary tangles were observed with Bielshowsky silver stain. The behavior changes of learning and memory were observed by open field test and passive avoidance test. Acetyleholine level, activities of acetycholinesterase and choline acetyltransferase of whole brain was detected by colorimetry method. The nitric oxide level of whole brain was detected by nitrate enzyme reduction method.

RESULTSExogenous human tau gene was expressed and an elevation of phosphor-tau protein level in 7 and 3-month transgenic mice's hippocampus andcerebrocortex was observed. The neurofibrillary tangles were observed in cerebrocortex of 7-month transgenic mice; the 7-month transgenic mice also presented an evident reduction of learning and memory ability and nitric oxide level of the whole brain, but not changes in acetylcholine level, acetycholinesterase activity, choline acetyltransferase activity and expression in whole brain.

CONCLUSIONTau transgenic mice (F10) can still inherit their parents' biologiccal characters, and develop learning and memory dysfunction awnodh san obvious decrease in nitric oxide level of whole brain in the 7-month old mice, suggesting a decrease of nitric oxide level of whole brain would be involved in the mechanism of learning and memory dysfunction in these transgenic mice.

Acetylcholine ; metabolism ; Acetylcholinesterase ; metabolism ; Animals ; Brain ; physiopathology ; Choline O-Acetyltransferase ; metabolism ; Humans ; Membrane Proteins ; genetics ; Memory Disorders ; genetics ; physiopathology ; Mice ; Mice, Transgenic ; Mutation ; Nitric Oxide ; metabolism

OBJECTIVETo investigate effect of chronic transauricular kindled seizures on passive-avoidance test memory retention in rats.

METHODSChronic transauricular kindled seizures was induced by repeated application of initially subconvulsive electrical stimulation through ear-clip electrodes once every 24 h until the occurrence of 3 consecutive clonic-tonic seizures. A passive avoidance test was used to measure memory retention ability. Morphological changes in neurons of hippocampal CA1 region was examined after HE staining. Histamine, gamma-aminobutyric acid (GABA) and glutamate levels in the hippocampus were measured by high performance liquid chromatography (HPLC).

RESULTChronic transauricular kindled seizures impaired passive-avoidance test memory retention in rats. The damaged CA1 neurons were observed and histamine content in the hippocampus markedly decreased 24 h after the end of kindling in the chronic transauricular kindled rats.

CONCLUSIONChronic transauricular kindled seizure impaired passive-avoidance test memory retention, and it might be due to the damaged CA1 neurons and a decrease of histamine in the hippocampus induced by epilepsy.

Animals ; Avoidance Learning ; Hippocampus ; metabolism ; pathology ; physiopathology ; Histamine ; metabolism ; Kindling, Neurologic ; Male ; Memory Disorders ; etiology ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Seizures ; metabolism ; pathology ; physiopathology ; gamma-Aminobutyric Acid ; metabolism

Cognitive impairment in diabetes (CID) is a severe chronic complication of diabetes mellitus, and its pathogenesis has not yet been fully understood. Increasing evidence has shown that the distribution and expression of N-methyl-D-aspartame receptor (NMDAR) and subunits NR2A and NR2B, which all participated in the development of the central nervous system and formation of learning and memory, are correlated with the occurrence and development of CID.
Central Nervous System ; Cognition Disorders ; complications ; genetics ; Diabetes Mellitus ; physiopathology ; Humans ; Memory ; Receptors, N-Methyl-D-Aspartate ; metabolism

Amyloid beta-Peptides ; metabolism ; Animals ; ErbB Receptors ; antagonists & inhibitors ; Humans ; Memory Disorders ; prevention & control ; Protein Kinase Inhibitors ; pharmacology

Mice ; Animals ; Alzheimer Disease/complications* ; Entorhinal Cortex/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Memory Disorders/etiology* ; Thalamus/metabolism* ; Disease Models, Animal

OBJECTIVETo observe the changes in the learning and memory functions and the hippocampal expression of phosphorylated cAMP response element-binding protein (pCREB) in rats with status epilepticus and generalized nonconvulsive status epilepticus.

METHODSStatus epilepticus (SE) and generalized nonconvulsive status epilepticus (GNCSE) was induced by pentylenetetrazol kindling in SD rats, and the learning and memory function changes of the kindled rats were assessed by means of Morris water-maze test and Y-maze test with alternative electric stimulation. Immunocytochemistry was used for analysis pCREB protein expression in the hippocampus of the rats.

RESULTSIn Morris water-maze test, the rats with SE showed prolonged mean escape latency (P<0.05), shortened swimming time in the platform quadrant (P<0.05), and reduced number of times of platform crossing (P<0.05) in the short term after kindling. But these changes were reversed and became normal a month after the kindling (P>0.05). In the Y-maze test with alternative electric stimulation, the total error (TE) of SE rats increased significantly in the short term after epilepsy (P<0.05), but recovered the normal level a month after kindling (P>0.05). The GNCSE rats showed prolonged mean escape latency at only certain time periods (P<0.05) in the short term, but with swimming time in the platform quadrant and number of platform crossings similar to the control group (P>0.05). The short-term TE of GNCSE rats increased significantly (P<0.05), but in the long term, TE was similar to that in the control group (P>0.05). The expression of pCREB decreased significantly in SE group in comparison with the control group in the short term.

CONCLUSIONEpileptic seizures can lead to learning and memory function impairment in rats, and SE seems to cause greater impact than GNCSE on the learning and memory functions. pCREB might be involved in the pathophysiology of learning and memory deficit in epileptic rats.

Animals ; CREB-Binding Protein ; metabolism ; Hippocampus ; metabolism ; physiopathology ; Kindling, Neurologic ; Maze Learning ; Memory Disorders ; physiopathology ; Pentylenetetrazole ; Rats ; Rats, Sprague-Dawley ; Status Epilepticus ; chemically induced ; metabolism ; physiopathology

OBJECTIVE: To study the effects of ketamine and alcohol on learning and memory in mice and its possible mechanism. METHODS: Forty mice were divided into 4 groups: normal control group, ketamine group, alcohol group, and alcohol plus ketamine group. Ketamine and alcohol were given by intraperitoneal injection and intragastric administration, respectively, 1 time per day, for 14 days. The ability of learning and memory in mice was tested by the method of step-down and Morris water maze. Acetylcholine (ACh) and 5-hydroxy tryptamine(5-HT) in mice brain tissue were analyzed for the possible mechanism. RESULTS: (1) Step-down: The treatment groups lessened the latency and added wrong times (P < 0.05). The number of errors in the combined treatment group significantly increased comparing with the single drug treatment group (P < 0.05). (2) Morris water-maze: The treatment groups prolonged the latency (P < 0.05), reduced the target quadrant activity time significantly (P < 0.05), and decreased the numbers of crossing the former platform significantly (P < 0.05). (3) Biochemical index determination: The concentrations of ACh and 5-HT in treatment groups decreased significantly (P < 0.05), showed a more decreasement comparing with the single drug treatment group. CONCLUSION Ketamine has a synergistic effect with alcohol on learning and memory impairment in mice, which may be related to the common inhibitive effect on the ACh and 5-HT.
Acetylcholine/metabolism* ; Alcohols/pharmacology* ; Animals ; Brain/physiopathology* ; Drug Synergism ; Ketamine/pharmacology* ; Male ; Maze Learning/drug effects* ; Memory/drug effects* ; Memory Disorders/physiopathology* ; Mice ; Mice, Inbred ICR ; Serotonin/metabolism* ; Spatial Behavior/drug effects*

This study is to investigate the protective effect of rosiglitazone (RSG) against learning and memory impairment of APP/PS1/tau transgenic mice. AD mice model was replicated by using 6-month APP/PS1/tau transgenic mice. The learning and memory ability of mice was evaluated by Morris water maze and Western blotting assays was applied to measure the phosphorylation and O-glycosylation of Tau and neurofilaments (NFs) protein. The results demonstrated that RSG could reverse the learning and memory deficits of 3 x Tg mice significantly. It was also found that RSG could suppress the hyperphosphorylation of Tau and NFs protein levels and increase the glycosylation expression of Tau and NFs proteins in 3 x Tg mice brain. Together, RSG ameliorates cognitive impairments of 3 x Tg mice via the alleviation of the hyperphosphorylated Tau and NFs proteins burden in the brain.
Alzheimer Disease ; Amyloid beta-Peptides ; Animals ; Brain ; drug effects ; Disease Models, Animal ; Glycosylation ; Learning ; drug effects ; Memory ; drug effects ; Memory Disorders ; drug therapy ; Mice ; Mice, Transgenic ; Neurofilament Proteins ; metabolism ; Phosphorylation ; Thiazolidinediones ; pharmacology ; tau Proteins ; metabolism