BRAIN MALARIA: PRESENTATION OF A CASE AND REVIEW OF THE LITERATURE

Malaria is a zoonotic disease caused by protozoa of the genus Plasmodium, acquired through the bite of a female of the Anopheles mosquito genus. The initial symptoms of malaria are usually non-speci?c, presenting with fever, moderate to severe dehydration, tachycardia and tachypnea, with systolic blood pressure usually within normal ranges and in some cases with headache, nausea and vomiting. The clinical diagnosis can be con?rmed by the presence of malarial retinopathy or the presence of parasites in at least 20% of the capillaries in the histopathological study of the brain. The drugs of choice are those derived from artemisinin, artesunate and quinine. We present a case of severe malaria with brain involvement.

Time dependent expression profiling of PTK2B and its relationship with Aβ, Tau and LRP-1 in hippocampus and blood of APPswe/PS1dE9 double-transgenic mouse / 中国应用生理学杂志

Objective: To uncover the time-dependent expression pattern of ptk2b gene and ptk2b-encoded protein, protein tyrosine kinase 2 beta(PTK2B), in the brain tissues of transgenic animal models of Alzheimer's disease (AD) and its relationship with the levels of Aβ1-42, phosphorylation of Tau (p-Tau) and low density lipoprotein receptor-related protein-1(LRP-1) in blood and brain tissues. Methods: In this study, 5-, 10- and 15-month-old APPswe/PS1dE9 double-transgenic mice harboring the genotype of AD confirmed by the gene test were divided into the 5-, 10- and 15-month-old experiment groups, and simultaneously, age-matched C57BL/6J mice were placed into the corresponding control groups, with 8 mice in each group. All mice were subjected to the Morris Water Maze for test of cognitive and behavioral ability. Expression profiles of PTK2B, Aβ1-42, p-Tau/Tau and LRP-1 in the hippocampus or blood of mice were quantified by using the immunohistochemistry staining, Western blot or enzyme-linked immunosorbent assay (ELISA), while the mRNA expression of ptk2b in the hippocampus was quantified by using the real-time quantitative polymerase chain reaction (qRT-PCR). Results: Results of experiment groups demonstrated that as mice aged, the expression levels of PTK2B, ptk2b mRNA, Aβ1-42 and p-Tau/Tau in the hippocampus were increased, and the expression of LRP-1 was decreased gradually. While in the blood, the level of Aβ1-42 was decreased, and the cognitive and behavioral ability was decreased in an age-dependent manner (all P＜ 0.05). However, comparisons among the control groups, only the age-dependent downregulation of LRP-1 were observed in hippocampus(P＜0.05), but other indicators had no significant differences (P＞0.05). Conclusion: In the hippocampus of APP/PS1 double-transgenic mice, the expressions of PTK2B, Aβ1-42 and p-Tau/Tau are upregulated, LRP-1 is downregulated, while cognitive and behavioral ability is decreased, and such changes are presented in a time-dependent manner.

Study of the neuroprotective effects and mechanisms of Tianma Gouteng Decoction on retinal ganglion cells in rat optic nerve crush model / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the mechanism of Tianma Gouteng Decoction on the protein molecular level in the optic nerve crush model rats.METHODS:Totally 36 participants 36 male Wistar rats were divided randomly into six groups(6 in every group):normal control group,negative control group,Tianma Gouteng Decoction treatment groups (con-centrations were 0.6g/mL,1.2g/mL,2.4g/mL respictively) and ginkgo biloba tablets positive control group (concentrations was 1.2mg/mL).Nothing was done in the normal control group.The optic nerve of right eye in the other groups was done with the optic nerve crush model.Normal control group and negative control group was treated only with water.The average grey scale values of the N-methyl-D-aspartic acid receptor 2B (NMDA2B) receptor protein,beta-amyloid protein (Aβ) in the average grey scale values were detected.RESULTS:The average grey scale value of Tianma Gouteng Decoction in low,medium and high dose groups about NMDA2B receptor protein was significantly less than that of the negative control group (all P＜0.001),and there was no significant difference with the positive control group (P=0.092,0.411,0.676),the difference between normal control group and negative control group was significant (P＜0.001).The high dose group of betaamyloid's average grey scale value reduced significantly than the negative control group (P=0.030,0.001).The low dose group than the negative control group was not obviously (P=0.614).The high dose group was not significantly different from the positive control group (P=0.927),the difference between normal control group and negative control group was significant (P＜0.001).CONCLUSION:Tianma Gouteng Decoction can go through the decrease of the NMDA2B receptor protein expression and the control of beta-amyloid deposition to reduce the retinal ganglion cell injury and apoptosis.

Acupuncture and Moxibustion Improves Learning-memory Ability of Alzheimer's Disease Rats Possibly by Up-regulating Serum Aβ Internalization Enzyme Contents / 针刺研究

OBJECTIVE: To observe the effect of acupuncture and moxibustion (AM) on learning-memory ability and expression of amyloid beta (Aβ) in the hippocampal dentate gyrus (DG) of Alzheimer's disease (AD) rats, so as to explore its mechanism underlying improvement of AD. METHODS: Forty male Wistar rats were randomly divided into normal, sham operation, model and AM groups (n＝10 in each). The AD model was established by bilateral hippocampal injection of Aβ1-42(5 µL). The AM was applied at "Baihui" (GV 20) and "Shenshu" (BL 23) for 15 min, once daily for 12 times. Morris water maze tests were used to assess the rats' learning-memory ability. The levels of serum Aβ1-42 and Aβ internalizing enzymes including transthyretin (TTR), lipoprotein lipase (LPL), alpha 2 macroglobulin (α 2M) and apolipoprotein E (ApoE) were detected by ELISA. The expression of Aβ1-42 in the hippocampal DG was detected by immunohistochemistry. RESULTS: Compared with the sham operation group, the average escape latency of location navigation test was significantly prolonged in the first 5 days and the last 3 days (P0.05). CONCLUSION: AM can improve the learning-memory ability of AD rats, which may be related to its effects in up-regulating the contents of serum Aβ internalizing enzymes and promoting the clearance of hippocampal Aβ. It suggests a protective role of AM on hippocampal neurons.

Effect of MG132 on Aβgeneration in SH-SY5Y cells / 中国病理生理杂志

[ ABSTRACT] AIM:To observe the influences of different concentrations of MG132 on apoptosis and beta-amyloid protein ( Aβ) generation in SH-SY5Y cells, and to explore the underlying mechanism.METHODS:SHSY-5Y cells were incubated with MG132 for 24 h.The final concentrations of MG132 were 2.5, 5 and 10μmol/L.The cell viability was de-termined by MTT assay.The cell apoptosis was assessed by flow cytometry.The levels of Aβwere measured by ELISA. The relative protein levels were detected by Western blot.RESULTS:In the SH-SY5Y cells, MG132 reduced the cell via-bility, induced the cell apoptosis, increased the level of Aβ, and increased the expression of the related proteins for Aβgeneration in a concentration-dependent manner.CONCLUSION: MG132 induces apoptosis and increases the levels of Aβ1-42 and Aβ1-40 by regulating the proteins related to Aβgeneration in the SH-SY5Y cells.

The Clinical Usefulness of Beta-Amyloid Positron Emission Tomography Imaging in the Elderly Patients: Case Series & Brief Review

The aim was to evaluate the diagnostic utility of beta-amyloid positron emission tomography (PET) in elderly patients with cognitive impairment in the clinical setting. Five subjects underwent beta-amyloid PET imaging to explore the cerebral beta-amyloid deposition. The two male patients with minor neurocognitive disorder due to Alzheimer's disease, who displayed similar degree of cognitive impairment and medial temporal atrophy but different in apolipoprotein E4 status, both showed negative for beta-amyloid PET. On the other hand, a female major neurocognitive disorder due to probable Alzheimer's disease patient was tested positive for beta-amyloid PET, with increased beta-amyloid density in frontal and parietal lobes. Beta-amyloid PET was also used for the differential diagnosis of neurocognitive disorder from other psychiatric disorders in two elderly patients. The results were negative but assisted the diagnositic confirmation. A female patient was determined to be a case of late-onset schizophrenia and a male patient was determined as delirium due to minor traumatic brain injury, persistent. Beta-amyloid PET imaging was able to demonstrate cerebral beta-amyloid deposition in major neurocognitive disorder due to probable Alzheimer's disease in visual scale. However, further studies are needed for its clinical utility in the minor neurocognitive disorders. Moreover, beta-amyloid PET imaging may provide additional information in diagnosing primary psychiatric disorders with new onset in the old age.

Effects of propofol on cognitive function in aged rats with hyperlipidemia / 中华行为医学与脑科学杂志

Objective To observe the effect of propofol on cognitive functions and hippocampus tissue in hyperlipidemia aged rats.Methods Seventy-six aged male SD rats were selected and randomly divided into basal diet with propofol injection (group PI), basal diet with normal saline injection(group N1), high-fat diet with propofol injection (group P2) and high-fat diet with normal saline injection (group P2), with 19 rats in each group.Eight weeks later,group P1 and P2 received intraperitoneal injection of propofol 100 mg · kg-1 · d-1 for 5 days.While in group N1 and N2, rats received the same intraperitoneal injection of equal volume normal saline.One day after the last injection, escape latency and space exploration were detected by Morris water maze in the next six days.One hour after the last water maze test, the serum and hippocampus were sampled to detect the expression of beta-amyloid protein and receptor for advanced glycation endproducts(RAGE) by immunohistochemical method and ELISA respectively.Results In place navigation tests,the escape incubation period(98.20±25.40)s in group P1 was obviously longer than that in N 1 group (47.50± 11.08) s (P＜ 0.01).Compared with P2 (99.79 ± 20.38) s, escape incubation period was shortened in N2 (50.70± 20.55) s (P＜ 0.05).There was no significantly difference between N2 and N1 (P＞0.05), while the escape incubation period in group P2 was longer than P1 (P＜ 0.05).In spatial probe test,platform passing number ((2.86 ±1.46)times) in group P1 were less than that in N1 group ((7.50± 1.70) times, P＜0.05).In group N2, the platform passing number ((6.60 ±3.91) times) were more than those in group P2 ((1.16 ±1.16)times, P＜0.05) while there was no significant difference between group N1 and N2 (P＞0.05).Times of crossing platform in group P2 were less than that in P1 group (P＜0.05).Compared with group N1((147.83±60.88) ng/L) and N2((152.73±87.50) ng/L) ,the expression of RAGE protein was increased in group P1((629.89±110.33) ng/L) and P2((229.89±53.20) ng/L) (P＜0.05).There was no significant difference between N1 and N2 groups(P＞0.05) ,while the expression of RAGE protein in P1 group was lower than that of P2(P＜0.05).In immunohistochemical test, positive expression cells in P1 ((18.49± 1.53) and P2 (25.67±3.08)) were higher than that in group N1(9.33±2.31) and group N2(12.14±2.52) (P＜0.05) ,while there was no significant difference between group N1 and N2(P＞0.05).Conclusions Anesthetic dose of propofol can injure spatial learning and memory ability in aged rats.Hyperlipidemia might act synergistically with propofol.

Effect of neuregulin on expressions of apoptosis and nuclear factor kappa B in hippocampus of Alzheimer's disease model rats / 中华行为医学与脑科学杂志

ObjectiveTo investigate the effect of neuregulin1β (NRG1β) on the learning memory abilities and the neuronal apoptosis and the expressions of nuclear factor kappa B (NFκB) in experimental Alzheimer's disease model in rats induced with beta-amyloid protein1-40 (Aβ1-40) injection.To explore the mechanisms of NRG in improving the capabilities of learning and memory.MethodsThirty adult healthy male wistar rats were randomly divided into control group (n =10),model group (n =10) and treated group (n =10).Alzheimer's disease models were established by stereotactically injecting Aβ1-40 into the left lateral ventricle,and treated by injecting NRG1β(0.3 μg · kg-1 ) into the right lateral ventricle.The learning and memory abilities of rats were evaluated with Y-electric maze before the experiment and 7 days after making Alzheimer's disease models and 14 days after treatment.HE staining was used to observe the structure of hippocampal neurons.The neuronal apoptosis of hippocampus was investigated by TUNEL assay.The expressions of NFκB in hippocampal neurons were determined with immunohistochemistry technique.ResultsCompared with control group (57.50 ± 1.58,7.20 ±1.03 ),the model group rats ( 59.50 ± 2.79,7.50 ± 1.08 ) showed low cognitive ability ( t =20.36,5.28,P ＜0.05 ),the hippocampal pyramidal cells of rats in the model group were sparse and disturbed pyramidal cells,noticeable neuron loss.The number of neuronal apoptosis and the expressions of NFκB increased significantly than those in control group (P＜0.05).Compared with model group (79.10 ±4.12,4.40 ±0.69),NRG1β strikingly improved cognitive ability ( 67.70 ± 4.90,5.80 ± 0.63 ) and normal cell structure ( t =5.63,4.69,P ＜ 0.05 ).The expressions of NFκB (25.90 ± 6.67 ) reduced while the number of neuronal apoptosis ( 23.50 ± 3.89 ) decreased markablely than those ( 41.10 ±7.95,29.30 ± 7.24) in model group(t =4.63,2.23,P ＜ 0.05).ConclusionNRG1β might decrease the neuronal apoptosis by inhibiting NFκB expressions,so that to improve the learning and memory abilities of experimental dementia rats.

Expression Change of Complement Regulator Genes of the Human Astrocytoma Cell Line after A beta1-42 and Interferon Gamma Administration

BACKGROUND: We determined the changes of complement regulator gene expression in the amyloid-beta1-42(A beta1-42) and interferon-gamma(IFN-gamma)-stimulated human astrocytoma cell line. METHODS: The human astrocytoma cell line, U373MG, was stimulated with IFN-gamma(62.5-1,000U/ml) in the presence or absence of aggregated A beta1-42(1-20micrometer) for 24 hours. Messenger RNA expression of C1 inhibitor(C1-INH), complement factor I(CFI), clusterin, vitronectin, decay accelerating factor(DAF), membrane cofactor protein(MCP), and CD59 was measured by quantitative real-time reverse transcriptase-PCR. RESULTS: IFN-gamma(final concentration, 500U/ml) markedly increased the expression of mRNA for C1-INH in a time dependent fashion. A beta1-42(final concentration, 2micrometer) induced a slight increase in the expression of C1-INH. Messenger RNAs for CFI and clusterin were minimally increased, but other regulators were unchanged or decreased by either A beta1-42 or IFN-gamma. IFN-gamma overrode A beta1-42-induced mRNA expression of C1-INH when the cells were treated with these two reagents together. CONCLUSION: Among the complement regulator genes in the human astrocytoma cell line, U373MG, only C1-INH was significantly up-regulated by IFN-gamma with or without A beta1-42 administration.

Neurobiology of Alzheimer's Disease

Alzheimer's disease(AD) is associated with a characteristic neuropathology. The major hallmarks of AD are senile plaques(SPs) and neurofibrillary tangles(NFTs). beta-amyloid protein(Abeta) is derived from the proteolysis of amyloid precursor protein(APP) and then converted to SPs. Mature SPs produce cytotoxicity through direct toxic effects and activation of microglia and complement. NFTs are composed of paired helical filaments(PHFs) including abnormally phosphorylated form of the microtubule-associated protein(MAP) tau and increased tau level in cerebrospinal fluid may be observed in most AD. The aggregation of Abeta and tau formation are thought to be a final common pathway of AD. Acetycholine, dopamine, serotonin, GABA and their receptors are associated with AD. Especially, decreased nicotinic acetylcholine receptors(nAChRs) in AD are reported. Genetic lesions associated with AD are mutations in the structural genes for the APP located on chromosome 21, presenilin(PSN)1 located on chromosome 14 and PSN2 located on chromosome 1. Also, trisomy 21, Apo-E gene located on chromosome 19, PMF locus, low density lipoprotein receptor-related protein and alpha-macroglobulin increase risk of AD. In this article, we will review about the neurobioloby of AD and some newly developed research areas.

The Effects of Psychotropic Drugs on the beta-Amyloid-Induced Cytotoxicity in PC12 Cells / 신경정신의학

OBJECTIVE: Amyloid beta protein(Abeta) has been regarded to be toxic to neurons in vitro. However, the mechanism of action leading to neuronal death remains unknown. In this study, we report the effects of psychotropic drugs, that are often prescribed for the improvement of psychotic and depressive symptoms in dementia of the Alzheimer's type, on the beta-amyloid-induced cytotoxicity in rat pheochromocytoma(PC12) cells. METHODS: We treated antipsychotics(chlorpromazine, haloperidol, and risperidone) and antidepressants(amitriptyline, fluoxetine, and moclobemide) at 0.1-10 microM concentrations before application of Abeta(10 microM), and compared with control in the absence of psychotropic drugs in cultured PC12 cells. RESULTS: 1) Chlorpromazine, haloperidol and risperidone significantly reduced Abeta-induced cytotoxicity in PC12 cells. 2) Amitriptyline, fluoxetine, and moclobemide significantly reduced Abeta-induced cytotoxicity in PC12 cells. CONCLUSION: Our results suggest that psychotropic drugs in the treatment of dementia of Alzheimer's type may protect the neural cells as well as control neurotransmitter activities.

Alzheimer's Disease and Apoptosis

Apoptosis is a form of cell death in which the cells shrink and exhibit nuclear chromatin condensation and DNA fragmentation, and yet maintain membrane integrity. Many lines of evidence have shown that brain neurons are vulnerable to degeneration by apoptosis. Also it has been suggested that apoptosis is one of the mechanism contributing neuronal loss in Alzheimer's disease(AD), since the conditions in the disease(A beta peptide, oxidative stress, low energy metabolism) are the inducers that activate apoptosis. Indeed some neurons in vulnerable regions of the AD brain show DNA damage, chromatin condensation, and apoptic bodies. Consistently, mutations in AD causative genes(Amyloid precursor protein, Presenilin-1 and Presenilin-2) increase A beta peptide1-42(Abeta1-42) and sensitize neuronal cell to apoposis. However, several lines of evidence have shown that the location of neuronal loss and A beta peptide deposition is not correlated in AD brain and transgenic mice brain over-expressing Abeta1-42. Taken together, these data may indicated that A beta peptide(and other causative factors of AD) can interact with other cellular insults or risk factors to exacerbate pathological mechansim of AD through apoptosis. Thus, this review discusses possible role and mechanism of apoptosis in AD.

Molecular Neurobiology of Alzheimer's Disease

Alzheimer's disease (AD), the most common dementia in the elderly, is associated with a characteristic neuropathology:extracellular neuritic plaques (NPs) and intraneuronal neurofibrillary tangles (NFTs). AD is diagnosed clinically on the basis of progressive cognitive impairment. However, the diagnosis of AD is only reliable if a histopathological examination at autopsy shows high numbers of NPs and NFTs particularly in the hippocampus and cerebral cortex. The major component of NP is beta-amyloid protein (Abeta), a fragment of the amyloid precursor protein (APP). NFTs are largely composed of paired helical filaments (PHFs) containing abnormally phospholylated form of the microtubule-associated protein (MAP), tau. A genetic etiology for AD has been established based on population survey. It is revealed that 25-40% of the AD patients are familial and the disease is inherited as an autosomal-dominant trait in most families. Age at onset patterns of AD patients in affected families had indicated that its distribution is bimodal with a cut-off age 58 years. Several mutations in the APP gene, located on chromosome 21, are linked to early-onset AD (EOAD). However, these account for only a small fraction of cases of EOAD. The remaining cases are associated with mutations in two other genes:one on chromosome 14 that encodes S182 (presenilin 1) and the other on chromosome 1 that encodes STM2 (presenilin 2). It is also known that inheritance of specific apolipoprotein E (apoE) alleles, located on chromosome 19, determines the risk and mean age of onset of late-onset AD (LOAD). In this review, we will briefly discuss the biology and hypothetical mechanisms of Abeta, presenilins, apoE and tau protein, those involved in the pathogenesis of AD.

Molecular Neurobiology of Alzheimer's Disease

Alzheimer's disease (AD), the most common dementia in the elderly, is associated with a characteristic neuropathology:extracellular neuritic plaques (NPs) and intraneuronal neurofibrillary tangles (NFTs). AD is diagnosed clinically on the basis of progressive cognitive impairment. However, the diagnosis of AD is only reliable if a histopathological examination at autopsy shows high numbers of NPs and NFTs particularly in the hippocampus and cerebral cortex. The major component of NP is beta-amyloid protein (Abeta), a fragment of the amyloid precursor protein (APP). NFTs are largely composed of paired helical filaments (PHFs) containing abnormally phospholylated form of the microtubule-associated protein (MAP), tau. A genetic etiology for AD has been established based on population survey. It is revealed that 25-40% of the AD patients are familial and the disease is inherited as an autosomal-dominant trait in most families. Age at onset patterns of AD patients in affected families had indicated that its distribution is bimodal with a cut-off age 58 years. Several mutations in the APP gene, located on chromosome 21, are linked to early-onset AD (EOAD). However, these account for only a small fraction of cases of EOAD. The remaining cases are associated with mutations in two other genes:one on chromosome 14 that encodes S182 (presenilin 1) and the other on chromosome 1 that encodes STM2 (presenilin 2). It is also known that inheritance of specific apolipoprotein E (apoE) alleles, located on chromosome 19, determines the risk and mean age of onset of late-onset AD (LOAD). In this review, we will briefly discuss the biology and hypothetical mechanisms of Abeta, presenilins, apoE and tau protein, those involved in the pathogenesis of AD.

Effects of long-term replacement therapy of estrogen or compound estrogen on the deposition of beta-amyloid protein in OVX rat hippocampal formation / 临床神经病学杂志

Objective To investigate the effects of long-term replacement therapy of estrogen or compound estrogen on the deposition of beta-amyloid protein (A?) in ovariectomy (OVX) rat hippocampal formation. Methods Fifty seven-month-old female Sprague-Dawley rats were randomly divided into five groups: normal control, SHAM, OVX, OVX plus 17beta-estradiol (OVX/ERT), and OVX plus compound nylestriol tablet (OVX/NL). The ovariectomy was performed in OVX, OVX/NL and OVX/ERT rats and drugs were administered orally in OVX/NL and OVX/ERT rats for 35 weeks after the ovariectomy. Then the rats in all groups were sacrificed. Immunohisto-chemistry of A?, cell counting and imaging system were used to determine the change of A? deposition levels in OVX rat hippocampal formation. Results The numbers and optical density of A?-positive neurons of all hippocampal subregions and dentate gyrus in OVX rats were markedly higher than those of normal control, SHAM,OVX/NL, and OVX/ERT rats( P