Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment. The main hypotheses about the pathogenesis of AD include the hypothesis of β-amyloid protein, the hypothesis of abnormal phosphorylation of Tau protein, and the hypothesis of neuroinflammation. In recent years, environmental pollutants have been considered as an important factor in causing neurological dysfunction. Common environmental pollutants include heavy metals, pesticides, polychlorinated biphenyls, microplastics, and air pollutants, all of which have been proven to have neurotoxicity. In this review, we not only discussed epidemiological and animal experimental studies that link environmental pollution with AD, but also summarized the mechanisms of action of relevant toxins, providing insights for studying the interrelationships between environmental pollutants and AD.
Animals ; Alzheimer Disease/chemically induced* ; Environmental Pollutants/toxicity* ; Neurodegenerative Diseases ; Plastics ; Amyloid beta-Peptides/metabolism*

PURPOSE: Alzheimer's disease (AD) results in memory impairment and neuronal cell death in the brain. Previous studies demonstrated that intracerebroventricular administration of streptozotocin (STZ) induces pathological and behavioral alterations similar to those observed in AD. Agmatine (Agm) has been shown to exert neuroprotective effects in central nervous system disorders. In this study, we investigated whether Agm treatment could attenuate apoptosis and improve cognitive decline in a STZ-induced Alzheimer rat model. MATERIALS AND METHODS: We studied the effect of Agm on AD pathology using a STZ-induced Alzheimer rat model. For each experiment, rats were given anesthesia (chloral hydrate 300 mg/kg, ip), followed by a single injection of STZ (1.5 mg/kg) bilaterally into each lateral ventricle (5 microL/ventricle). Rats were injected with Agm (100 mg/kg) daily up to two weeks from the surgery day. RESULTS: Agm suppressed the accumulation of amyloid beta and enhanced insulin signal transduction in STZ-induced Alzheimer rats [experimetal control (EC) group]. Upon evaluation of cognitive function by Morris water maze testing, significant improvement of learning and memory dysfunction in the STZ-Agm group was observed compared with the EC group. Western blot results revealed significant attenuation of the protein expressions of cleaved caspase-3 and Bax, as well as increases in the protein expressions of Bcl2, PI3K, Nrf2, and gamma-glutamyl cysteine synthetase, in the STZ-Agm group. CONCLUSION: Our results showed that Agm is involved in the activation of antioxidant signaling pathways and activation of insulin signal transduction. Accordingly, Agm may be a promising therapeutic agent for improving cognitive decline and attenuating apoptosis in AD.
Agmatine/*therapeutic use ; Alzheimer Disease/*chemically induced/*drug therapy ; Animals ; Cognition Disorders/*chemically induced/*drug therapy ; Disease Models, Animal ; Male ; Rats ; Streptozocin/*toxicity

OBJECTIVE: To investigate the effects of Deoxygedunin on Aβ deposition, learning memory, and oxidative stress induced by D-galactose combined with AlCl in model rats with Alzheimer's disease and its possible mechanism. METHODS: Male SD rats were randomly divided into three groups (=12):control group, model group (AD) and intervention group (AD+Deo). Morris water maze test was used to detect learning/memory and cognitive function in rats.Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and malondialdehyde (MDA) contents in homogenate of hippocampus were detected by enzyme-linked immunosorbent assay (ELISA).Tau protein expression in rat cerebral cortex was detected by immunohistochemistry.Western blot was used to detect the expressions of extracellular signal regulated kinase 1(ERK1), protein kinase B (PKB) and tropomyosin-related kinase B (TrkB) on TrkB signaling pathway. RESULTS: The results of water maze test showed that D-galactose combined with AlCl induced a significant increase in the escape latency compared with the control group (<0.05).Deoxygedunin could reverse the increase of the escape latency of the model group (<0.05).On the 7th day after removal of the platform, the model group showed an increase in escape latency compared with the control group and the intervention group (<0.01), and the number of crossing platforms was declined (<0.05); The results of immunohistochemistry and ELISA showed that the expressions of Aβ and tau protein in the model group were increased significantly compared with those of the control group (<0.01).The activities of SOD and GSH-Px were decreased significantly and the content of MDA was increased significantly.Compared with the model group, Deoxygedunin could reverse the increase of the expressions of Aβ and tau protein (<0.01), the decrease of SOD and GSH-Px activities (<0.05) and the increase of the MDA content (<0.05).Western blot results showed that Deoxygedunin treatment reversed the decreased phosphorylation levels of TrkB, AKT and ERK1 in hippocampus of the model group. CONCLUSIONS Supplement of Deoxygedunin can significantly reverse Aβ deposition, oxidative stress and cognitive deficits by activating the TrkB signal transduction pathway, which suggest that Deoxygedunin may serve as a promising therapeutic candidate for attenuating AD-like pathological dysfunction induced by D-galactose combined with AlCl.
Alzheimer Disease ; chemically induced ; Animals ; Disease Models, Animal ; Galactose ; Hippocampus ; Limonins ; Male ; Maze Learning ; Rats ; Rats, Sprague-Dawley

The aim of the present study was to explore the correlation between ptk2b/PTK2B (protein tyrosine kinase 2 beta, a ptk2b-encoded protein) and the level of low density lipoprotein receptor-related protein-1 (LRP-1), as well as to uncover the relationship between the changes in beta amyloid protein (Aβ) levels in blood and brain and the expression of ptk2b in Aβ-induced cognitive dysfunction mice. A total of 64 3-month-old C57BL/6J mice were divided randomly into the experimental group and control group. All mice underwent the intracerebroventricular (i.c.v.) intubation. Mice in the experimental group received the i.c.v. infusion of oligomeric Aβ
Alzheimer Disease ; Amyloid beta-Peptides/metabolism* ; Animals ; Brain ; Cognitive Dysfunction/chemically induced* ; Disease Models, Animal ; Focal Adhesion Kinase 2 ; Hippocampus/metabolism* ; Mice ; Mice, Inbred C57BL ; Peptide Fragments

Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes, public health decision making, and primary prevention synthesis. Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies. Biomarkers are generally classified into three groups: biomarkers of exposure, effect, and susceptibility.The main body compartments that store lead are the blood, soft tissues, and bone; the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurological disorders, such as brain damage, mental retardation, behavioral problems, nerve damage, and possibly Alzheimer's disease, Parkinsons disease, and schizophrenia. This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.
Alzheimer Disease ; chemically induced ; metabolism ; pathology ; physiopathology ; psychology ; Animals ; Behavior ; drug effects ; Biomarkers ; metabolism ; Brain ; metabolism ; pathology ; physiopathology ; Brain Diseases ; chemically induced ; pathology ; physiopathology ; Environmental Exposure ; adverse effects ; Humans ; Lead ; pharmacokinetics ; toxicity ; Lead Poisoning ; etiology ; metabolism ; pathology ; physiopathology ; psychology ; Neurotoxicity Syndromes ; etiology ; metabolism ; pathology ; physiopathology ; psychology ; Parkinson Disease, Secondary ; chemically induced ; metabolism ; pathology ; physiopathology ; psychology ; Schizophrenia ; chemically induced ; metabolism ; pathology ; physiopathology

OBJECTIVETo explore the potential effect of Guizhi plus Gegen Decoction (GGD) in improving learning and memory of lipopolysaccharides (LPS) induced neuroinflammatory mice and its possible mechanisms.

METHODSTotally 63 male ICR mice were randomly divided into 5 groups, i.e., the normal control (n = 13), the model group (n = 13), the low dose GGD group (n = 10), the high dose GGD group (n = 14), and the positive control group (n = 13). Mice were intraperitoneally injected with LPS (0.33 mg/kg) to induce Alzheimer's disease (AD) model. Mice in the high and the low dose GGD groups were administered with 12 g/kg or 6 g/kg by gastrogavage for 4 successive weeks. Mice in the control group were intraperitoneally injected with minocycline (50 mg/kg) for 3 days. By the end of treatment LPS were injected 4 h before behavior test each day, and then behavior test was conducted in mice of each group. Effect of GGD on learning and memory of AD mice was observed by using open field test, novel object recognition task, and Morris water maze.

RESULTSOpen field test showed there was no statistical difference in the movement time and the movement distance among all groups (P > 0.05), suggesting that LPS and GGD had no effect on locomotor activities of mice. In novel object recognition test, AD mice spent significantly shorter time to explore novel object after they were induced by LPS (P < 0.05), while for AD mice in the low and high dose GGD groups, their capacities for exploration and memory were significantly improved (P < 0. 05, P < 0.01). Results of Morris water maze showed that AD mice exhibited increased escape latency (P < 0.05) and spent much less time in swimming across the original platform (both P < 0.05). However, AD mice in the low and high dose GGD groups had obvious shortened latency and increased time percentage for swimming (P < 0.05, P < 0.01).

CONCLUSIONGGD possessed certain improvement in learning and memory disorder of LPS induced AD mice.

Alzheimer Disease ; chemically induced ; drug therapy ; psychology ; Animals ; Drugs, Chinese Herbal ; therapeutic use ; Lipopolysaccharides ; adverse effects ; Male ; Memory Disorders ; prevention & control ; Mice ; Mice, Inbred ICR ; Neuritis ; chemically induced ; drug therapy ; psychology ; Phytotherapy

OBJECTIVE: To investigate the effects of rutaecarpine on high glucose-induced Alzheimer's disease-like pathological and cognitive dysfunction and its mechanism in rats. METHODS: Adult male SD rats were randomly divided into three groups (n=20): control group, high glucose group and rutaecarpine group. Rats in the control group were fed with conventional feed and tap water. The rats in the high glucose group were fed with conventional feed and 20% sucrose water. The rutaecarpine group was fed with fodder contain 0.01% rutaecarpine and 20% sucrose water. Morris water maze test was used to detect learning and memory and cognitive function of three groups rats after 24 weeks of feeding. Western blot analysis was used to detect tau protein at Thr205 and Ser214 sites in each group. Phosphorylation levels of GSK-3β in serine 9 site (S9-GSK-3β) and PP2A at cycline 307 site (Y307-PP2AC) were also detected. Immunohistochemistry further confirmed tau protein at Thr205 site in each group both in hippocampus and cortex. RESULTS: Compared with the control group, Morris water maze results showed that the latency of finding the hidden platform of the rats in high glucose group was increased significantly and the number of crossing platforms and the target quadrant residence time were significantly decreased (all P＜0.05). Immunohistochemistry showed that the phosphorylation level of tau protein at Thr205 site was significantly increased in the high glucose group compared with the control group, and the phosphorylation level of tau protein at Thr205 site in the rutaecarpine group was higher than that in the high glucose group. Western blot analysis showed that the phosphorylation level of tau protein in the high glucose group was significantly increased at Thr205 and Ser214 site compared with the control group, but the phosphorylation level of pS9-GSK-3β was significantly decreased (all P ＜0.05). Compared with the high glucose group, the latency of finding the hidden platform of the rats in rutaecarpine group was significantly decreased, and the number of crossing platforms and the target quadrant residence time were significantly increased (both P＜0.05). Compared with the high glucose group, the phosphorylation levels of tau protein at Thr205 and Ser214 sites showed a significant decrease, but the phosphorylation level of pS9-GSK-3β was significantly increased (all P＜0.05). CONCLUSION Rutaecarpine can alleviate AD-like cognitive dysfunction induced by high glucose, possibly by enhancing pS9-GSK-3β phosphorylation, down-regulating GSK-3β activity, and thus reducing hyperphosphorylation of tau-associated sites.
Alzheimer Disease ; chemically induced ; drug therapy ; Animals ; Cognitive Dysfunction ; chemically induced ; drug therapy ; Glucose ; Glycogen Synthase Kinase 3 beta ; chemistry ; Indole Alkaloids ; pharmacology ; Male ; Maze Learning ; Phosphorylation ; Quinazolines ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; tau Proteins ; chemistry

OBJECTIVETo explore the protective effect of tetramethylpyrazine (TMP) on the learning and memory function in D-galactose (D-gal)-lesioned mice.

METHODSC57BL/6 mice were injected (s.c.) 2% D-gal for 40 days (100 mg x kg(-1) x d(-1)). Normal saline, TMP, and Huperzine A were respectively given by intragastric administration in different groups from the third week. Learning and memory ability was tested with Morris water maze for 5 days at the sixth week. After completion of behavioral test, the mice were sacrificed by decapitation. The brain was rapidly removed, and the cortex and hippocampus were separated. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the cortex were determined. At the same time, the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), the binding sites (Bmax) and the affinity (KD) of M-cholinergic receptor in the cortex, and Bmax and KD of N-methyl-D-aspartate (NMDA) receptor in the hippocampus were determined.

RESULTSIn this model group, (1) The deficit of learning and memory ability, (2) elevated MDA content and lowered SOD activity, (3) decreased AChE activity and M-cholinergic receptor binding sites in the cortex, and (4) lowered NMDA receptor binding sites were observed in the hippocampus, as compared with the normal control. TMP could markedly (1) attenuate cognitive dysfunction, (2) lower MDA content and elevate SOD activity, (3) increase the activity of ChAT and AChE, and M-cholinergic receptor binding sites in the cortex in the mice treated with D-gal. NMDA receptor binding sites were also increased in the hippocampus in the treated mice.

CONCLUSIONTMP can significantly strengthen antioxidative function, improve central cholinergic system function, protect NMDA receptor activity, and thus enhance the learning and memory ability in D-gal-lesioned mice.

Alzheimer Disease ; chemically induced ; metabolism ; physiopathology ; Animals ; Galactose ; Hippocampus ; metabolism ; Male ; Maze Learning ; drug effects ; Mice ; Mice, Inbred C57BL ; Neuroprotective Agents ; pharmacology ; Pyrazines ; pharmacology ; Receptors, Muscarinic ; metabolism

BACKGROUNDA model of simulated Alzheimer's disease (AD) induced by aggregated amyloid protein (Abeta(1-40)) was built in Wistar rats to observe the behavioral and pathological changes of Abeta(1-40) and the effect of hypodermic insulin injected on the function of study and memory and the expression of Abeta(1-40) from the CA1 area of the hippocampus.

METHODSExperimental groups were as follows: contrast, simulated AD model, contrast of Nacl, and insulin treated. The simulated AD model was built by microinjection of aggregated Abeta(1-40) at the CA1 area of the hippocampus, and was hypodermically injected with 0.9% NaCl (1 ml/kg) and insulin (0.1 U/kg) separately the next day. Two weeks after the modeling, the four groups were tested with water maze about the study and memory function of rats. Three weeks after the injection, the expression of Abeta(1-40) at the CA1 area of the hippocampus was examined by pathological tests (HE, Congo red) and immunohistochemical methods.

RESULTSThe study and memory abilities of rats were ameliorated significantly by the place navigation test and the spatial probe test after the application of insulin. Insulin could decrease the expression of Abeta(1-40) at the CA1 area of the hippocampus to reduce the pathological damage of Abeta(1-40) to the hippocampal area of rats.

CONCLUSIONSThe injection of aggregated Abeta(1-40) to the hippocampal area could simulate the behavioral and pathological features of AD such as the difficulty of study and memory and the damage to neurons. Insulin is effective to improve the function of study and memory and amend the pathological damage of simulated AD model rats. The results give a experimental proof of insulin in the clinical treatment of AD.

Alzheimer Disease ; chemically induced ; drug therapy ; psychology ; Amyloid beta-Peptides ; analysis ; toxicity ; Animals ; Cognition ; drug effects ; Disease Models, Animal ; Hippocampus ; chemistry ; pathology ; Insulin ; pharmacology ; therapeutic use ; Male ; Peptide Fragments ; analysis ; toxicity ; Rats ; Rats, Wistar

OBJECTIVETo investigate the possible mechanism of the electroacupuncture for improvement of learning and memory in rats of Alzheimer's disease (AD).

METHODSSixty Wistar rats were randomly divided into a normal group, a normal saline group, a model group, a western medication group and an electroacupuncture group, 12 rats in each group. The AD rat model was established by injecting Streptozocin (STZ) into lateral cerebral ventricle, except the rats in the normal saline group injecting Normal Saline with the same dose and in normal group with no injection. The western medication group was treated with intragastric administration of Memantine, and in the electroacupuncture group, the electroacupuncture was given at "Baihui" (GV 20), "Dazhui" (CV 14), "Taixi" (KI 3), "Shenshu" (BL 23), "Zusanli" (ST 36), once each day, 7 days for a course, and lasted for 4 courses. The other three groups were fed in routine way and without any treatment. The learning and memory ability was assessed by Morris water maze and the expression of Abeta positive cells of the hippocampus and superoxide dismutase (SOD) activity were determined by immunohistochemistry and visible spectrophotometer colorimetry.

RESULTSCompared with the normal group and the normal saline group, the Abeta protein expression was significantly increased in the model group (both P < 0.01), and the SOD activity was obviously decreased (both P < 0.01). After treatment, as compared with the model group, the Abeta protein expression was significantly decreased (both P < 0.01), and the SOD activity was obviously increased (both P < 0.01) in the electroacupuncture group and western medication group.

CONCLUSIONElectroacupuncture treatment can reduce the Abeta protein expression and increase the SOD activity of the hippocampus so as to improve learning and memory ability in the AD rats.

Alzheimer Disease ; chemically induced ; enzymology ; physiopathology ; therapy ; Amyloid beta-Peptides ; metabolism ; Animals ; Disease Models, Animal ; Electroacupuncture ; Gene Expression Regulation, Enzymologic ; Hippocampus ; enzymology ; metabolism ; Humans ; Learning ; Male ; Memory ; Random Allocation ; Rats ; Rats, Wistar ; Streptozocin ; adverse effects ; Superoxide Dismutase ; genetics ; metabolism