OBJECTIVETo study the effect of taurine on lead-induced damage to the ability of learning and memory.

METHODSUsing NADPH-d histochemistry method to study the change of rat NOS positive neurons in hippocampus. Rats in experimental groups were fed with different doses of lead in drinking water (0.011, 0.110 g/L), and different doses of taurine (5, 10 g/kg).

RESULTSTaurine (10 g/kg) could increase the number of NOS positive neurons in CA1 and dentate gyrus subregion in hippocampus of rats exposed to lead. The number of NADPH-d positive neurons in CA1 and dentate gyrus subregion for low lead (0.011 g/L) and high taurine (10 g/kg) group (51.80 +/- 4.68, 47.40 +/- 4.20, respectively) were higher than those in the low lead (0.011 g/L) group (41.20 +/- 5.32, 39.87 +/- 3.81, respectively, P < 0.05).

CONCLUSIONTaurine may antagonize lead-induced damage to the ability of learning and memory.

Animals ; Hippocampus ; enzymology ; Lead ; toxicity ; Learning ; drug effects ; Long-Term Potentiation ; drug effects ; Male ; Memory ; drug effects ; Memory Disorders ; chemically induced ; enzymology ; Neurons ; enzymology ; Neuroprotective Agents ; pharmacology ; Nitric Oxide Synthase ; metabolism ; Rats ; Rats, Wistar ; Taurine ; pharmacology

Animals ; Blotting, Western ; Cell Differentiation ; drug effects ; Embryonic Stem Cells ; cytology ; enzymology ; Isoenzymes ; analysis ; Mice ; Neurons ; enzymology ; Protein Kinase C ; analysis ; Tretinoin ; pharmacology

BACKGROUNDAlzheimer disease (AD) is a neurodegenerative disease related to aging. At present, its pathological mechanisms remain unclear. Family members of the renin-angiotensin system (RAS) play a role in neuronal plasticity, as well as formation of learning and memory. In this study, we explore the effects of altered angiotensin-converting enzyme (ACE), and investigate the possible mechanisms of perindopril, an ACE inhibitor, on brain structure and function in a rat model of AD, as well as the role that ACE plays in AD.

METHODSSixty Sprague-Dawley rats were selected and randomly divided into 3 groups: control, AD, and perindopril. Each group consisted of 20 rats, with 10 rats for determining pathology, and the remaining 10 rats for quantifying ACE activity. The rat AD model was established by stereotactically injecting amyloid beta protein (A-beta) 1-42 into the right hippocampus. Learning and memory functions were tested using the Y-type electric maze. The number and morphology of abnormal neurons were determined by haematoxylin and eosin staining. Amyloid deposition was measured by Congo red staining. Finally, ACE activity was estimated by spectrophotometry.

RESULTSCompared with the control group, the number of times needed to escape electrical stimuli increased (23.70 +/- 3.13, P < 0.001), the number of normal neurons in the CA1 region was reduced (density of 96.5 +/- 32.6/mm, P < 0.001), amyloid deposition was obvious, and ACE activity increased ((34.4 +/- 6.6) nmol x g(-1) x min(-1), P < 0.001) in the AD group. In the perindopril group, the number of times needed to escape electrical stimuli decreased (18.50 +/- 3.66, P < 0.001), the number of abnormal neurons increased (density of CA1 neurons was 180.8 +/- 28.5/mm, P < 0.001), amyloid deposition was reduced, and ACE activity was down-regulated ((26.2 +/- 6.2) nmol x g(-1) x min(-1), P < 0.001).

CONCLUSIONSACE activity increased in the brains of AD rats. Perindopril improved learning and memory in AD rats, which correlated with decreased ACE activity and delayed AD pathogenesis.

Alzheimer Disease ; enzymology ; pathology ; physiopathology ; Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Brain ; drug effects ; enzymology ; pathology ; Disease Models, Animal ; Maze Learning ; drug effects ; physiology ; Neurons ; drug effects ; metabolism ; pathology ; Peptidyl-Dipeptidase A ; metabolism ; Perindopril ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the effect of Bushen Huoxue Decoction (BHD) on the orphan receptor (Nurr1) and tyrosine hydroxylase (TH) in the brain of rats with Parkinson's disease (PD).

METHODSOne hundred and twenty SD rats were divided into 100 in the model group and 20 in the normal control group, fifty-eight SD rats from the model group, established into PD model successfully by injuring their substantia nigra (SSN) with 6-hydroxydopamine, were divided equally into the model group and the test group, and they were treated with saline and BHD, respectively, for eight successive weeks. The change in the rats' behavior before and after treatment was observed by counting the cycles of rotation induced by apomorphine injection; the pathology of neurons, level of Nurr1 mRNA expression, and amount of TH positive cells in SSN were observed after treatment.

RESULTSThe rats' behavior was improved in the tested group significantly, the rotation cycle after treatment being 84.0 ± 20.0 cycles/40 min, which was significantly lower than that in the model group (377.0 ± 62.3 cycles/40 min, P<0.01). Besides, the Nurr1 mRNA expression and TH positive cell in the test group were 0.97 ± 0.15 and 49.40 ± 14.72, respectively, which were significantly higher than those in the model group, 0.22 ± 0.03 and 5.45 ± 2.58, respectively (all P<0.01).

CONCLUSIONBHD could treat PD by enhancing the Nurr1 mRNA expression, increasing the TH content in brain, and promoting the repairing of injured neuron in cerebral SSN.

Animals ; Behavior, Animal ; drug effects ; Brain ; drug effects ; enzymology ; pathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Gene Expression Regulation ; drug effects ; Neurons ; drug effects ; enzymology ; pathology ; Nuclear Receptor Subfamily 4, Group A, Member 2 ; genetics ; metabolism ; Parkinson Disease ; drug therapy ; enzymology ; pathology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; drug effects ; metabolism ; pathology ; Tyrosine 3-Monooxygenase ; metabolism

Intravenous anesthetics are known to cause amnesia, but the underlying molecular mechanisms remain elusive. To identify a possible molecular mechanism, we recently turned our attention to a key intracellular signaling pathway organized by a family of mitogen-activated protein kinases (MAPKs). As a prominent synapse-to-nucleus superhighway, MAPKs couple surface glutamate receptors to nuclear transcriptional events essential for the development and/or maintenance of different forms of synaptic plasticity (long-term potentiation and long-term depression) and memory formation. To define the role of MAPK-dependent transcription in the amnesic property of anesthetics, we conducted a series of studies to examine the effect of a prototype intravenous anesthetic propofol on the MAPK response to N-methyl-D-aspartate receptor (NMDAR) stimulation in hippocampal neurons. Our results suggest that propofol possesses the ability to inhibit NMDAR-mediated activation of a classic subclass of MAPKs, extracellular signal-regulated protein kinase 1/2 (ERK1/2). Concurrent inhibition of transcriptional activity also occurs as a result of inhibited responses of ERK1/2 to NMDA. These findings provide first evidence for an inhibitory modulation of the NMDAR-MAPK pathway by an intravenous anesthetic and introduce a new avenue to elucidate a transcription-dependent mechanism processing the amnesic effect of anesthetics.
Amnesia ; chemically induced ; enzymology ; Anesthetics, Intravenous ; pharmacology ; Animals ; Cells, Cultured ; Extracellular Signal-Regulated MAP Kinases ; drug effects ; metabolism ; Hippocampus ; cytology ; drug effects ; enzymology ; Long-Term Potentiation ; drug effects ; physiology ; Memory ; drug effects ; physiology ; Mitogen-Activated Protein Kinase 1 ; drug effects ; Mitogen-Activated Protein Kinase 3 ; drug effects ; Neurons ; drug effects ; enzymology ; Propofol ; pharmacology ; Rats ; Receptors, N-Methyl-D-Aspartate ; metabolism ; Signal Transduction ; drug effects ; physiology ; Transcriptional Activation ; drug effects

OBJECTIVELuteolin, a flavone, has considerable neuroprotective effects by its anti-oxidative mechanism. However, it is still unclear whether luteolin can protect neurons against oxygen-glucose deprivation/reperfusion (OGD/R) induced injury.

METHODAfter 2 hours oxygen-glucose deprivation and 24 hours reperfusion treatment in primary cultured hippocampal neurons, the neuron viability, survival rate and apoptosis rate were evaluated by MTT assay, lactate dehydrogenase (LDH) leakage assay and Hoechst staining, respectively. The activity of Na+/K+ -ATPase was examined in cultured neurons or in the hippocampus of SD rats treated by 10 minutes global cerebral ischemia and followed 24 hours reperfusion.

RESULTTreatment by OGD/R markedly reduced neuronal viability, increased LDH leakage rate and increased apoptosis rate. Application of luteolin (10-100 micromol x L(-1)) during OGD inhibited OGD/R induced neuron injury and apoptosis in a dose-dependent manner. Compared to the control group or OGP/R-treated neurons, the activity of Na+/K+ -ATPase was significantly suppressed in global ischemia/reperfusion group or OGD/R-treated neurons. Application of luteolin during ischemia or OGD preserved the Na+/K+ -ATPase activity. Furthermore, inhibition of Na+/K+ -ATPase with ouabain attenuated the protective effect afforded by luteolin.

CONCLUSIONThe data provide the evidence that luteolin has neuroprotective effect against OGD/R induced injury and the protective effect may be associated with its ability to improve Na+/K+ -ATPase activity after OGD/R.

Animals ; Antioxidants ; pharmacology ; Apoptosis ; drug effects ; Cell Hypoxia ; Glucose ; metabolism ; Luteolin ; pharmacology ; Neurons ; drug effects ; enzymology ; metabolism ; pathology ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; enzymology ; metabolism ; pathology ; prevention & control ; Sodium-Potassium-Exchanging ATPase ; metabolism

OBJECTIVETo investigate the effect of lithium on hippocampal cholecystokinin (CCK) and neuronal nitric oxide synthase (nNOS) positive neurons and its relationship to the learning and memory ability of lead exposed rats.

METHODSWistar rats were randomly divided into the control group, the lead group, four lead + LiCl (3, 30, 300, 3,000 mg/kg) groups. Four lead + LiCl groups were fed with food containing 3, 30, 300, 3,000 mg/kg LiCl respectively. The lead + LiCl groups and the lead group were administered with distilled water containing 0.2% PbAc. The body weight was measured and the difference of body development was observed. Y-maze test was used for studying the effects of lead on the learning and the memory ability in rats. ABC immunohistochemistry was used for investigating the changes of CCK positive neurons in hippocampus of lead-exposed rats.

RESULTSCompared with the control group and the lead + LiCl groups, the learning and memory ability of lead exposed rats was significantly higher (P < 0.05). The number of CCK positive neurons in hippocampus lead exposed rats fed with lithium (3, 30, 300 mg/kg) was significantly higher than that in the lead exposed rats (P < 0.05).

CONCLUSIONThe lead may damage the learning-memory ability of the rats. It might be related to the changes of CCK positive neurons in hippocampus in lead exposed rats. The lithium of the low dose might play an important role in preventing lead-induced damages.

Animals ; Cholecystokinin ; metabolism ; Dose-Response Relationship, Drug ; Hippocampus ; drug effects ; metabolism ; Immunohistochemistry ; Lead ; toxicity ; Lithium ; pharmacology ; Male ; Maze Learning ; drug effects ; Memory ; drug effects ; Neurons ; enzymology ; Nitric Oxide Synthase ; metabolism ; Random Allocation ; Rats ; Rats, Wistar

This in vitro study evaluated the detrimental effect of acute gamma (gamma)-irradiation on rat immature hippocampal neurons. Rat immature hippocampal neurons (0.5 day in vitro) were irradiated with 0~4 Gy gamma-rays. Cytotoxicity was analyzed using a lactate dehydrogenase release assay at 24 h after gamma-irradiation. Radiation-induced cytotoxicity in immature hippocampal neurons increased in a dose-dependent manner. Pre-treatments of pro-apoptotic caspase inhibitors and anti-oxidative substances significantly blocked gamma-irradiation-induced cytotoxicity in immature hippocampal neurons. The results suggest that the caspase-dependent cytotoxicity of gamma-rays in immature hippocampal cultured neurons may be caused by oxidative stress.
Amifostine/pharmacology ; Animals ; Antioxidants/pharmacology ; Caspase 3/metabolism/radiation effects ; Catechin/analogs & derivatives/pharmacology ; Cell Survival/radiation effects ; Cells, Cultured/cytology/enzymology/*radiation effects ; Dose-Response Relationship, Radiation ; Female ; *Gamma Rays ; Hippocampus/cytology/enzymology/*radiation effects ; L-Lactate Dehydrogenase/radiation effects ; Neurons/cytology/enzymology/*radiation effects ; Poly(ADP-ribose) Polymerases/drug effects ; Pregnancy ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effects of Erzhi Pill (二至丸,EZP) on nerve cell apoptosis in senescence model rats.

METHODSThe rats model of senescence was established by peritoneal D-galactose injection combined with thymusectomy. Forty SD rats were randomized into four groups, the normal control group, the senescence model group, the EZP treated group, and the vitamins treated group, 10 in each group. The rats were made into senescence model except those in the normal group. In the same time of D-galactose injection, the rats were treated respectively with distilled water, EZP 4.32 g/kg, and vitamins E and C 0.06 g/kg daily for 6 weeks via intragastric infusion. The index of main viscera (as brain, testis, etc.), serum levels of superoxide dismutase (SOD) activity, and total anti-oxidation capacity (T-AOC) were measured after a 6-week treatment. Meanwhile, the cerebral cortex neuronal apoptosis proportion and mitochondrial membrane potential (MMP) were detected by flow cytometry.

RESULTSBoth EZP and vitamins E and C treatments showed effects on increasing testis index and serum level of T-AOC, reducing the percentage of neuronal apoptosis in the cerebral cortex, and elevating MMP in the aging rats model.

CONCLUSIONSEZP could inhibit the cerebral cortex neuron apoptosis and maintain the mitochondrial function in the senescent process of rats induced by peritoneal D-galactose injection combined with thymusectomy. It also shows antioxidation effect to some extents.

Aging ; blood ; drug effects ; Animals ; Antioxidants ; metabolism ; Apoptosis ; drug effects ; Cerebral Cortex ; cytology ; Drugs, Chinese Herbal ; pharmacology ; Male ; Matrix Metalloproteinases ; metabolism ; Neurons ; cytology ; drug effects ; enzymology ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; blood

Brain-derived neurotrophic factor (BDNF)is the richest neurophin in brain tissue and may act as an activity-dependent neuronal survival factor. In vitro, BDNF plays an important role in preventing cortical neurons from hypoxia-induced neurotoxicity. It could induce a variety of cellular responses such as cell growth, survival, differentiation, and anti-apoptosis mainly via activating mitogen-activated protein kinase (MAPK) and Ca2+/calmodulin-dependent kinase (CaMK) signaling pathways. And among these multiple signaling pathways there is growing evidence of complicated cross talk.
Animals ; Brain-Derived Neurotrophic Factor ; pharmacology ; physiology ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; Calcium-Calmodulin-Dependent Protein Kinases ; drug effects ; physiology ; Cells, Cultured ; Humans ; Mitogen-Activated Protein Kinases ; drug effects ; physiology ; Neurons ; cytology ; drug effects ; enzymology ; Signal Transduction