One of the major social issues nowadays is the aging society. Korea is already an aging society, and 63 cities and districts are ultra-aged societies where the rate of people older than 65 yr exceeds 20%. Among them, more than 67% are women. These statistics reveal the importance of healthcare for older women. Disease and disability of older women are very closely related to the loss of female sex hormones after menopause. Major hormone-dependent aging problems in women such as osteoporosis, Alzheimer's disease (AD), urinary incontinence, and coronary atherosclerosis were surveyed in this review, and the key role of hormones in those diseases and hormone replacement therapy (HRT) were summarized. We expect that this review would provide some understanding of factors that must be considered to give optimal care to older women for healthy lives.
Aged ; Aged, 80 and over ; Aging/*physiology ; Alzheimer Disease/drug therapy/metabolism/*physiopathology ; Female ; Gonadal Steroid Hormones/*metabolism/physiology/therapeutic use ; Hormone Replacement Therapy ; Humans ; Middle Aged ; Osteoporosis/drug therapy/metabolism/*physiopathology

OBJECTIVETo study the effects of Dipsacus total saponins on the ability of learning and memory and its mechanism of action.

METHODSForty rats were randomly divided into blank control group, model group, Dipsacus group and positive control group (n = 10), general situation of rats were observed, the ability of learning and memory of rats was tested by Square water maze, the activities of acetylcholinesterase (AChE)and choline acetyltransferase (ChAT) of hippocampus in rats were measured using double antibody sandwich method.

RESULTSDuring the period of treatment, general situation had no obvious change in model group, but general situation and the ability of activity were gradually improved in Dipsacus group and positive control group. Compared with blank control group, the swimming time was obviously prolonged and the number of mistakes was obviously increased at different time, the activity of AChE was significantly enhanced and the activity of ChAT was significantly decreased in model group. Compared with model group, the swimming time was obviously shortened and the number of mistakes was obviously reduced at different time, the activities of AChE were significantly decreased and the activities of ChAT were significantly enhanced in Dipsacus group and positive control group; Compared with positive control group, the swimming time and the number of mistakes at different time and the activities of AChE and ChAT had no significant difference in Dipsacus group.

CONCLUSIONDipsacus total saponins can improve the ability of learning and memory in Alzheimer' s disease(AD) rats, its mechanism of 'action may be related to regulating ACh metabolism of hippocampus.

Acetylcholine ; metabolism ; Acetylcholinesterase ; metabolism ; Alzheimer Disease ; drug therapy ; physiopathology ; Animals ; Choline O-Acetyltransferase ; metabolism ; Dipsacaceae ; chemistry ; Disease Models, Animal ; Hippocampus ; drug effects ; Learning ; drug effects ; Memory ; drug effects ; Rats ; Saponins ; pharmacology

There is a close correlation between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) in the course of pathophysiological processes. The neuroprotective action of glucagon-like peptide 1 (GLP-1), a latest drug for clinical treatment of T2DM, is being more deeply investigated at present, and a novel therapeutic strategy for AD with GLP-1 has been proposed boldly. This review mainly discussed the correlation of pathogenesis between T2DM and AD, the synthesis and secretion of GLP-1, the distribution and physiological effects of GLP-1 receptor in the brain, and the progresses on the study of GLP-1 in the treatment of AD.
Alzheimer Disease ; drug therapy ; physiopathology ; Amyloid beta-Peptides ; drug effects ; metabolism ; Animals ; Brain ; metabolism ; Diabetes Mellitus, Type 2 ; physiopathology ; Glucagon-Like Peptide 1 ; pharmacology ; therapeutic use ; Glucagon-Like Peptide-1 Receptor ; Humans ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Receptors, Glucagon ; metabolism

Glucagon-like peptide-1 (GLP-1) has been endorsed as a promising and attractive agent in the treatment of type 2 diabetes mellitus (T2DM). Both Alzheimer's disease (AD) and T2DM share some common pathophysiologic hallmarks, such as amyloid beta (Abeta), phosphoralation of tau protein, and glycogen synthase kinase-3. GLP-1 possesses neurotropic properties and can reduce amyloid protein levels in the brain. Based on extensive studies during the past decades, the understanding on AD leads us to believe that the primary targets in AD are the Abeta and tau protein. Combine these findings, GLP-1 is probably a promising agent in the therapy of AD. This review was focused on the biochemistry and physiology of GLP-1, communities between T2DM and AD, new progresses of GLP-1 in treating T2MD and improving some pathologic hallmarks of AD.
Alzheimer Disease ; drug therapy ; metabolism ; physiopathology ; Amino Acid Sequence ; Amyloid beta-Peptides ; metabolism ; Animals ; Brain ; drug effects ; metabolism ; physiopathology ; Diabetes Mellitus, Type 2 ; drug therapy ; metabolism ; physiopathology ; Glucagon-Like Peptide 1 ; chemistry ; metabolism ; pharmacology ; Glucose ; metabolism ; Humans ; Molecular Sequence Data ; tau Proteins ; antagonists & inhibitors ; metabolism

OBJECTIVETo observe the effect of a Chinese medicine compound, Naoerkang (NEK), on amyloid-beta peptide (1-42; Aβ(1-42)) and matrix metalloproteinase-9 (MMP-9) expressions in the hippocampus of Alzheimer's disease (AD) model rats.

METHODSA total of 48 male Sprague Dawley (SD) rats were randomly divided into normal control, untreated, and piracetam groups, and low-dose, medium-dose, and high-dose NEK groups, with 8 rats in each group. The 5-μL aggregated Aβ(1-42) (2 μg/μL) were injected into both CA1 areas of the hippocampus in the rats to establish an AD model, whereas the normal control was treated with the same dose of normal saline. The rats in the NEK groups were treated with a high, medium, or low dose of NEK [60 g/(kg·d), 30 g/(kg·d), and 15 g/(kg·d)], respectively, intragastrically for 28 days; piracetam (0.375 g/kg, intragastrically) was consecutively administered in the piracetam group; and normal saline was applied in the normal control and untreated groups. A Y-maze test was used for behavioral study to test the learning and memory abilities. Aβ(1-42) and MMP-9 expressions in the hippocampus was determined immunohistochemically, and the results were analyzed by image acquisition and an analysis system.

RESULTSAggregated Aβ(1-42) induced obvious learning and memory dysfunction, as well as up-regulation of Aβ(1-42) expression in the hippocampus. Compared with those in the normal control group, the learning and memory abilities of rats in the untreated group significantly decreased (P<0.01), and the expression of Aβ(1-42) was significantly increased (P<0.01). Twenty-eight days after different treatments, compared with those in the untreated group, the learning and memory abilities of AD model rats in the piracetam, low-dose, medium-dose and high-dose NEK groups were significantly improved (P<0.01 or P<0.05), and the expression of Aβ(1-42) in the hippocampus decreased (P<0.01 or P<0.05), and MMP-9 increased (P<0.01 or P<0.05), especially in the high-dose NEK group.

CONCLUSIONNEK might play a role of anti-dementia by increasing the expression of MMP-9 in the hippocampus of AD model rats, resulting in the reduction of the quantity of Aβ(1-42) and improvement in learning and memory ability in AD model rats.

Alzheimer Disease ; drug therapy ; metabolism ; pathology ; physiopathology ; Amyloid beta-Peptides ; metabolism ; Animals ; CA1 Region, Hippocampal ; drug effects ; enzymology ; pathology ; physiopathology ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hippocampus ; drug effects ; metabolism ; pathology ; physiopathology ; Immunohistochemistry ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Memory ; drug effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the alteration of beta-amyloid (Abeta) and glutamate transporter in the brain cortex of diabetes mellitus (DM) rats and the underlying mechanism.

METHODSThe rats were randomly divided into control, DM, DM +NaCl, and DM +LiCl groups and diabetes was induced by streptozotocin. The activity of glycogen synthase kinase-3 (GSK-3) and the function of glutamate transporter were measured by 32P-labelling. The amount of Abeta was determined by enzyme-linked immunosorbentassay.

RESULTSIn DM group, the level of Abeta40 increased (P < 0.01), but the function of glutamate transporter was impaired (P < 0.05). The activity of GSK-3 was stimulated (P < 0.05). Compared with DM group, the level of Abeta40 was restored (P < 0.01), and the function of glutamate transporter was enhanced (P < 0.05) in LiCl treated group, accompanied by a decreased activity of GSK-3.

CONCLUSIONOverproduction of Abeta and impaired glutamate transporter exist in DM rats, and increase of GSK-3 may play a crucial role in this process.

Alzheimer Disease ; etiology ; Amino Acid Transport System X-AG ; metabolism ; Amyloid beta-Peptides ; metabolism ; Animals ; Cerebral Cortex ; metabolism ; Diabetes Mellitus, Experimental ; complications ; drug therapy ; physiopathology ; Glycogen Synthase Kinase 3 ; metabolism ; Lithium Chloride ; pharmacology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the influence of Qingkailing (QKL) on learning and memory abilities, global neurotransmitter and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway of senescence accelerated mouse-prone/8 (SAMP8) mice with Alzheimer's dementia (AD).

METHODSSAMP mice were modeled and divided into the model group, the QKL group and the doneppezil hydrochloride group, all treated for 90 days. And a control group was set up with senescence accelerated mouse-resistance/1 (SAMR1) mice. Morris water maze was used to test the learning and memory abilities of mice; contents of acetylcholine (Ach) and monoamine neurotransmitters in brain were measured by HPLC; levels of Grb2-associated binder-1 (Gab1), AKT and phospho-serine/threonine protein kinase B (PAKT473) were evaluated by Western-blot.

RESULTSCompared with the control group, in the model group, the average escape latency detected by hidden platform trial and reverse trial on the 3rd day was higher (P < 0.01); levels of Ach, 5-hydroxytryptamine (5-HT) and Gab1 were lower (P < 0.01, P < 0.05 and P < 0.01), respectively. As compared with the model group, the escape latency (within the 2nd to 5th day) decreased (P < 0.01), levels of Ach and 5-HT increased (P < 0.05), and Gab1 protein expression increased (P < 0.01) in the QKL treated group after treatment, in addition, the level of phosphorylated AKT protein significantly increased (P < 0.05).

CONCLUSIONQKL could improve the learning and memory ability of AD model mice, which is probably related to its function in increasing cerebral Ach, 5-HT and activating PI3K/AKT pathway.

Alzheimer Disease ; drug therapy ; physiopathology ; Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Learning ; drug effects ; Male ; Memory ; drug effects ; Mice ; Mice, Mutant Strains ; Phosphatidylinositol 3-Kinases ; metabolism ; Phytotherapy ; Proto-Oncogene Proteins ; metabolism ; Receptor Protein-Tyrosine Kinases ; metabolism ; Signal Transduction ; drug effects

BACKGROUNDHyperbaric oxygen (HBO) and Ginkgo biloba extract (e.g., EGB 761) were shown to ameliorate cognitive and memory impairment in Alzheimer's disease (AD). However, the exact mechanism remains elusive. The aim of the present study was to investigate the possible mechanisms of HBO and EGB 761 via the function of nuclear factor kappa-B (NF-κB) pathway.

METHODSAD rats were induced by injecting β-amyloid 25-35 into the hippocampus. All animals were divided into six groups: Normal, sham, AD model, HBO (2 atmosphere absolute; 60 min/d), EGB 761 (20 mg·kg-1·d-1 ), and HBO/EGB 761 groups. Morris water maze tests were used to assess cognitive, and memory capacities of rats; TdT-mediated dUTP Nick-End Labeling staining and Western blotting were used to analyze apoptosis and NF-κB pathway-related proteins in hippocampus tissues.

RESULTSMorris water maze tests revealed that EGB 761 and HBO significantly improved the cognitive and memory ability of AD rats. In addition, the protective effect of combinational therapy (HBO/EGB 761) was superior to either HBO or EGB 761 alone. In line, reduced apoptosis with NF-κB pathway activation was observed in hippocampus neurons treated by HBO and EGB 761.

CONCLUSIONSOur results suggested that HBO and EGB 761 improve cognitive and memory capacity in a rat model of AD. The protective effects are associated with the reduced apoptosis with NF-κB pathway activation in hippocampus neurons.

Alzheimer Disease ; chemically induced ; drug therapy ; physiopathology ; therapy ; Amyloid beta-Peptides ; toxicity ; Animals ; Disease Models, Animal ; Ginkgo biloba ; chemistry ; Hyperbaric Oxygenation ; Male ; Maze Learning ; drug effects ; Memory Disorders ; drug therapy ; therapy ; NF-kappa B ; metabolism ; Plant Extracts ; therapeutic use ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the effect of the total flavonoids of Jiawei Wuzi Yanzong prescription on the Voltage-gated calcium channel of the CA1 pyramidal cell of rat hippocampus.

METHODThe inward calcium current was recorded by the whole-cell patch clamp and the amplitude of it was thought to observe the effect of Abeta25-35 and the total flavonoids. The hippocampus of rat was separated and cut into slices. Active pyramidal cells of slices were chosen for the whole-cell patch clamp recording. After exposure to Abeta25-35, voltage steps (500 ms) were used to depolarize stepwise in a range from 50 to +50 mV (increment: 5 mV). An inward Ca2+ current which was suggested to be survey was evoked. Application of the total flavonoids was to be observed if it had effect on this voltage-depended inward current.

RESULTAbeta25-35 could enhance the calcium current to induce intracellular calcium overload. The amplitude of the control group was--(157.1 +/- 19.9) pA, but after application of Abeta25-35 the current enhanced to--(323.2 +/- 23.4) pA. When the total flavonoids at concentration of 125, 250, 500 g x L(-1) were added, the current declined to--(257.9 +/- 31.6), - (196.4 +/- 29.8) and--(169.3 +/- 34.0) pA, respectively.

CONCLUSIONAbeta-induced intracellular calcium overload may be one of neurotoxic of beta-amyloid peptide. The total flavonoids of Jiawei Wuzi Yanzong prescription can suppress inward calcium current to protect neurons.

Alzheimer Disease ; drug therapy ; metabolism ; physiopathology ; Amyloid beta-Peptides ; metabolism ; Animals ; CA1 Region, Hippocampal ; cytology ; drug effects ; physiology ; Calcium Channels ; genetics ; physiology ; Disease Models, Animal ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Electrophysiology ; Female ; Flavonoids ; chemistry ; pharmacology ; Humans ; Male ; Peptide Fragments ; metabolism ; Prescription Drugs ; chemistry ; pharmacology ; Pyramidal Cells ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo research Angelica tenuissima Nakai (ATN) for use in novel Alzheimer's disease (AD) therapeutics.

METHODSThe effect of a 30% ethanol extract of ATN (KH032) on AD-like cognitive impairment and neuropathological and neuroinflammatory changes induced by bilateral intracerebroventricular injections of β-amyloid (Aβ) peptide (Aβ) was investigated. Male C57Bl/6 mice were randomly divided into 4 groups, 10 in each group. KH032-treated groups were administrated with a low or high dose of KH032 (50 and 200 mg/kg, respectively), intragastrically for 16 days; distilled water was applied in the sham and negative groups. Open fifield test, Y maze and Morris water maze test were used for behavior test and cognitive ability. In addition, the neuroprotective effects of KH032 in Aβ-infused mice on the histopathological markers [neuronspecific nuclear protein (NeuN), Aβ] of neurodegeneration were examined. The levels of glial fibrillary acidic protein (GFAP), NeuN, phosphorylation extracellular signal-regulated kinase (ERK)/ERK, brain-derived neurotrophic factor (BDNF), phosphorylation cAMP response element-binding (CREB)/CREB protein expression were measured by Western blot.

RESULTSKH032 treatment ameliorated cognitive impairments, reduced the overexpression of Aβ, and inhibited neuronal loss and neuroinflammatory response in the Aβ-infused mice. Moreover, KH032 treatment enhanced BDNF expression levels in the hippocampus. Finally, KH032 treatment increased phosphorylation of ERK1/2 and CREB, vital for ERK-CREB signaling.

CONCLUSIONSKH032 attenuated cognitive defificits in the Aβ-infused mice by increasing BDNF expression and ERK1/2 and CREB phosphorylation and inhibiting neuronal loss and neuroinflflammatory response, suggesting that KH032 has therapeutic potential in neurodegenerative disorders such as AD.

Alzheimer Disease ; drug therapy ; pathology ; physiopathology ; Amyloid beta-Peptides ; Angelica ; chemistry ; Animals ; Brain ; pathology ; Brain-Derived Neurotrophic Factor ; metabolism ; Cognitive Dysfunction ; complications ; drug therapy ; physiopathology ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Disease Models, Animal ; Male ; Maze Learning ; drug effects ; Memory, Short-Term ; drug effects ; Mice, Inbred C57BL ; Neurogenesis ; drug effects ; Neuroglia ; drug effects ; metabolism ; pathology ; Neurons ; drug effects ; metabolism ; pathology ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Phosphorylation ; drug effects ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Plaque, Amyloid ; drug therapy ; pathology ; physiopathology ; Signal Transduction ; drug effects