AIMTo study the changes of synaptic plasticity in rat model with Alzheimer disease (AD).

METHODSAD rat model was conducted by D-galactose intraperitoneal injection combined with lesions of nucleus basalis of Meynert (nbM). Behavioral performance, LTP in dentate gyrus and synaptic morphology in hippocampal CA1 were observed.

RESULTS(1) Escape latencies in place test in model rats were longer than that in control rats, and swimming time and distance between the two groups in platform quadrant were significant differently (P < 0.01). (2) The numerical density (Nu) and surface density (Su) of synaptic contact zones markedly decreased (P < 0.01) in model rats. (3) Augment of population spike (PS) in perforant path-dentate gyrus of model rats after high frequency stimulation was smaller than that of the control (P < 0.05).

CONCLUSIONThe results suggest that the decreased synaptic plasticity in hippocampus could responsible for the impairment of spatial learning of model rats.

Alzheimer Disease ; physiopathology ; Animals ; Basal Nucleus of Meynert ; pathology ; Disease Models, Animal ; Female ; Galactose ; pharmacology ; Hippocampus ; physiopathology ; Long-Term Potentiation ; Male ; Neuronal Plasticity ; Rats ; Rats, Wistar

OBJECTIVETo observe the protective effect of Panax notoginseng saponins (PNS) on the level of synaptophysin ptotein in brain in rat model with Alzheimer's disease (AD).

METHODThe AD rat models were established by intra-peritoneal injection of D-galactose combined with excitatory neurotoxin ibotenic acid injection into bilateral nbM. The activity and content of synaptophysin protein in brain were determined by immunohistochemistry analysis.

RESULTPNS could reduce the lesion of level of synaptophysin protein in brain, as compared with those of model group's rats.

CONCLUSIONPNS plays a protective role by reducing down of the level of synaptophysin protein in brain in lesion of AD animal model.

Alzheimer Disease ; chemically induced ; metabolism ; pathology ; Animals ; Basal Nucleus of Meynert ; drug effects ; pathology ; Brain ; metabolism ; pathology ; Galactose ; toxicity ; Ginsenosides ; isolation & purification ; pharmacology ; Ibotenic Acid ; toxicity ; Neuroprotective Agents ; isolation & purification ; pharmacology ; Panax ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Rats, Wistar ; Synaptophysin ; metabolism

OBJECTIVE: To explore the effect of tanshinone IIA (TanIIA) on calcium current induced by beta-amyloid protein 25-35 (Abeta25-35) in neurons of nucleus basalis of Meynert (nbM). METHODS: Cell acute dissociated technique and the whole-cell recording model of patch-clamp technique of single-cell were used. The voltage-dependent calcium current in neurons of nbM was recorded in SD rats first. Then the effect of TanIIA on the voltage-dependent calcium current in the neurons was assayed. The change of calcium current induced by Abeta25-35 as well as the effect of TanIIA on the change of calcium current induced by Abeta25-35 in neurons of nbM were analyzed. RESULTS: Extracellular fluid containing different concentrations of TanIIA was irrigated, respectively. The peak current did not change obviously. There was no difference in current density between the TanIIA group and the control group at 0 mV (P>0.05). Extracellular fluid containing 200 nmol/L Abeta25-35 was irrigated after the normal calcium current recorded under whole patch clamp, and the peak current changed obviously. There was distinct difference in the current density between the Abeta group and the control group at 0 mV (P<0.05). Extracellular fluid containing Abeta25-35 and different concentrations of TanIIA were irrigated after the normal calcium current was recorded under whole patch clamp, respectively, and the peak current did not change. There was no difference in current density between the TanIIA +Abeta group and the control group at 0 mV (P>0.05). CONCLUSION In vitro, TanIIA could inhibit the calcium current amplification induced by Abeta25-35 in neurons of nbM. TanIIA may protect neurons against the toxicity of Abeta and decrease the inward flow of Ca(2+).
Abietanes ; pharmacology ; Amyloid beta-Peptides ; toxicity ; Animals ; Basal Nucleus of Meynert ; cytology ; metabolism ; Calcium ; metabolism ; Calcium Channels ; drug effects ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Female ; Male ; Neurons ; cytology ; metabolism ; Neuroprotective Agents ; pharmacology ; Patch-Clamp Techniques ; Peptide Fragments ; toxicity ; Rats

Of all patients with dementia, 50-60% have dmentia of Alzheimer's type, and vascular dementia represents 17-29% of all cases. Other common causes of dementia include drugs, toxins, intracranial masses, anoxia, infections, neurodegenerative disorders, metabolic disorders, and chronic infalmmatory disorders. Treatment approach to demented patients may account for drug therapy in Al-zheimer's disease, because about 10-23% of patients have coexisting vascular dementia and dementia of Alzheimer's type. Dementia other than Alzheimer's disease also show various degrees of impairment of cognitive and non-cognitive function such as depression, psychosis and other behavioral problems, therefore pharmacological treatment for specific symptoms should be provided and therapy should be directed toward treating the underiying cuases as well. Alzheimer's disease (AD) is the most important of all the degenerative disease with progressive impairment of cognitive function and neuropsychiatric disturbance. Neuropathologic investigations have shown that cholinergic neuronal loss is seen in the nucleus basalis of Meynert, and choline acetyltransferase and acctylcholine esterase are decreased in the cerebral cortex. This hypothesis led to attempts to correct the dificiency with cholinomimetic agents and proved to be effective in some patients. However, there have been no pharmacologic agent proved to be suce-ssful. The most recent of these is the reversible acetyl cholinesterase inhibitor with long half life and high affirnity to CNS, Aricept (donepezil), which produces great improvement in cognitive function in clinical trials in Europe and US without compromized hepatotoxicity. The other pathophysiology of AD includes wide range of neurotransmitter imbalances and cortical atrophy, so that combined treatment apporach such as choinergic/serotonergic drug and cholinergic/somatostatinergic drug should be considered. As a preventive approach, neurotrophic factor, which may delay degenerative process of cholinergic neuron, is clinically valuable when administrated directly into ventricles. In many cases, amyloid deposits are seen as the distinctive neuropathology of AD, and the evidence that amyloid peptide genes found to be on chromosome 21 will lead the gene therapy for this diseases. As the disease advances, various degrees of neuropsychiatric distrubance become so marked that may be helped by treatment of associated depression, anxiety, disruptive behavior, and psychotic symtoms with appropriate psychotropic medication. However, these drugs may make patients confused, requiring reduced ro withdrawal of the medication. therefore, a careful attempt should be made, since demands on enviromental apporach and behavioral therapy are high.
Alzheimer Disease ; Amyloid ; Anoxia ; Anxiety ; Atrophy ; Basal Nucleus of Meynert ; Cerebral Cortex ; Choline O-Acetyltransferase ; Cholinergic Neurons ; Cholinesterases ; Chromosomes, Human, Pair 21 ; Dementia ; Dementia, Vascular ; Depression ; Drug Therapy ; Europe ; Genetic Therapy ; Half-Life ; Humans ; Neurodegenerative Diseases ; Neurotransmitter Agents ; Plaque, Amyloid ; Psychotic Disorders

Thiamine deficiency is generally accepted as the primary etiologic factor for the Wernicke encephalopathy in human and for the similar neurologic symptoms in thiamine depleted experimental animals. Although pyrithiariiineinduced thiamine deficiency has been known to produce histopathologic lesions within many nuclei of the rat brain, the pathogenic mechanisms involved have not been clarified. Furthermore, the effect of thiamine deprivation on the nature and anatomic distribution of neurotransmitter changes has not been fully explored. The present studies were undertaken to investigate - morphological changes of the basal nucleus of Meynert and vestibular nucleus in thiamine deficient rats induced by pyrithiamine and thiamine deficient diet. For this purpose immunohistochemical stain for choline acetyltransferase was performed. Fifty healthy Sprague-Dawley strain rats weighing about 150 gm, were divided into 10 control group and 40 thiamine deficient group. Animals in thiamine deficient group were treated with daily intraperitoneal injection of pyrithiamine( 50 ug/lOOgm of BW/dbLy, Sigma Co.) for 9 days and were continuously given thiamine deficient diet until to be sacrificed. Thiamine deficient rats were subdivided into 3 groups according to different stages of neurologic manifestations ; the early group, the beginning stage of anorexia, hypothermia and weight loss without neurologic manifestations(sacrificed day ; 9th-13th day) the intermediate group, the developing stage of gait ataxia and hypotonia(sacrificed day ; 17th-19th day) the late group, the established stage of tremor, convulsion and back arching(sacrificed day ; 23th-26th day). All animals were anesthetized with sodium pentobarbital(40mg/kg, I.p.) and perfused in vivo through the ascending aorta with 10% neutral buffered formalin or 4% paraformaldehyde-0. 1% glutaraldehyde in PBS, and then brains were removed. Luxol-fast blue and cresyl violet stain was performed according to routine paraffin method for observing morphologic changes in basal nucleus of Meynert and vestibular nucleus. In addition immunohistochemical stains in the same regions were performed by free floating method in cell culture plate. All preparations were observed with a light microscope. The results obtained were as follows ; 1. Sequential changes of the neurologic manifestations in thiamine deficient rats were weight loss, hypothermia and ariorexia on the 9th-10th day, followed by gait ataxia and hypotonia on the 13th-15th day, and then tremor, convulsion and back arching on the 22th-26th day. 2. Glial proliferation was noted in the basal nucleus of the early group but not in the vestibular nucleus. Atrophy and pyknosis of neurons in basal nucleus and vestibular nucleus were shown in the intermediate group and marke neuronal loss and edematous tissue necrosis were noted in the late group. 3. Choline acetyltransferase immurforeactivity in the basal nucleus and vestibular nucleus was markedly positive in the early group as well as control group, moderately positive in the intermediate groupand minimally positive in the late group. It is suggested that the extent of neuronal damage in thiamine deficient rats is proportional to the duration of thiamine depletion. And the data presented here may account for: the regional susceptability and reversibility of certain symptoms in thiamine deficient rats.
Animals ; Anorexia ; Aorta ; Atrophy ; Basal Nucleus of Meynert* ; Brain ; Cell Culture Techniques ; Choline O-Acetyltransferase* ; Choline* ; Coloring Agents ; Diet ; Formaldehyde ; Gait Ataxia ; Glutaral ; Humans ; Hypothermia ; Injections, Intraperitoneal ; Muscle Hypotonia ; Necrosis ; Neurologic Manifestations ; Neurons ; Neurotransmitter Agents ; Paraffin ; Pyrithiamine ; Rats* ; Rats, Sprague-Dawley ; Seizures ; Sodium ; Thiamine Deficiency ; Thiamine* ; Tremor ; Viola ; Weight Loss ; Wernicke Encephalopathy