OBJECTIVETo explore the effects of angiotensin-(1-7) on the learning and memory abilities and the expressions of glial fibrillary acidic protein (GFAP) and glial cell line-derived neurotrophic factor (GDNF) in the hippocampus of diabetic rats.

METHODSForty male SD rats were randomly assigned into 4 groups, namely the control group, diabetic group, Ang(1-7)-treated diabetic group (DM1 group), and Ang-(1-7)- and Mas receptor antagonist A779-treated diabetic group (DM2 group). Diabetic rat models were established by a single intraperitoneal injection of streptozotocin (60 mg/kg). The cognitive function of the rats was assessed with Morris water maze (MWM) test. The expressions of GDNF in the hippocampus were examined by RT-PCR and Western blot. Nissl staining was performed to evaluate the morphological changes in rat hippocampus. The expressions of glial fibrillary acidic protein (GFAP, a key indicator of astrocytic reactivity) and caspase-3 were measured by immunohistochemistry.

RESULTSCompared with the control group, the diabetic rats exhibited significantly impaired learning and memory abilities (P<0.05) with lowered expression of GDNF and increased caspase-3 expression in the hippocampus (P<0.05) and significant hippocampal neuronal and astrocyte injuries (P<0.05). Treatment with Ang(1-7) obviously improved the learning and memory abilities of the diabetic rats (P<0.05), increased GDNF and GFAP expressions (P<0.05), lowered caspase-3 expression (P<0.05), and increased the number of surviving neurons in the hippocampus (P<0.05). Such effects of Ang(1-7) effect was blocked by treatment with A779 of the diabetic rats.

CONCLUSIONAng(1-7) can alleviate cognitive dysfunction in diabetic rats possibly by up-regulating the expressions of GFAP and GDNF and promoting neuron survival in the hippocampus.

Angiotensin I ; pharmacology ; Animals ; Astrocytes ; Caspase 3 ; metabolism ; Cognition ; Cognition Disorders ; Diabetes Mellitus, Experimental ; physiopathology ; Glial Cell Line-Derived Neurotrophic Factor ; metabolism ; Glial Fibrillary Acidic Protein ; metabolism ; Hippocampus ; cytology ; metabolism ; Male ; Memory ; Neurons ; Peptide Fragments ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Streptozocin

BACKGROUNDLittle attention has been paid to the role of subcortical deep gray matter (SDGM) structures in type 2 diabetes mellitus (T2DM)-induced cognitive impairment, especially hippocampal subfields. Our aims were to assess the in vivo volumes of SDGM structures and hippocampal subfields using magnetic resonance imaging (MRI) and to test their associations with cognitive performance in T2DM.

METHODSA total of 80 T2DM patients and 80 neurologically unimpaired healthy controls matched by age, sex and education level was enrolled in this study. We assessed the volumes of the SDGM structures and seven hippocampal subfields on MRI using a novel technique that enabled automated volumetry. We used Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA) scores as measures of cognitive performance. The association of glycosylated hemoglobin (HbA1c) with SDGM structures and neuropsychological tests and correlations between hippocampal subfields and neuropsychological tests were assessed by partial correlation analysis in T2DM.

RESULTSBilaterally, the hippocampal volumes were smaller in T2DM patients, mainly in the CA1 and subiculum subfields. Partial correlation analysis showed that the MoCA scores, particularly those regarding delayed memory, were significantly positively correlated with reduced hippocampal CA1 and subiculum volumes in T2DM patients. Additionally, higher HbA1c levels were significantly associated with poor memory performance and hippocampal atrophy among T2DM patients.

CONCLUSIONSThese data indicate that the hippocampus might be the main affected region among the SDGM structures in T2DM. These structural changes in the hippocampal CA1 and subiculum areas might be at the core of underlying neurobiological mechanisms of hippocampal dysfunction, suggesting that degeneration in these regions could be responsible for memory impairments in T2DM patients.

Aged ; CA1 Region, Hippocampal ; pathology ; physiopathology ; Diabetes Mellitus, Type 2 ; pathology ; physiopathology ; Female ; Hippocampus ; pathology ; physiopathology ; Humans ; Magnetic Resonance Imaging ; Male ; Memory Disorders ; etiology ; pathology ; Middle Aged ; Neuropsychological Tests

OBJECTIVETo evaluate the effect of Nigella sativa (NS) extract on memory performance and its possible mechanisms in scopolamine (Sco)-induced spatial memory impairment model using Morris water maze test.

METHODSThirty-two male Wistar rats were randomly divided into four groups. The control group received saline instead of both NS extract and Sco. The Sco group was treated by saline for two weeks, and was injected by Sco (2 mg/kg, intraperitoneally) 30 min before each trail in Morris water maze test. Sco+NS 200 and Sco+NS 400 groups were daily treated by 200 or 400 mg/kg of NS (intraperitoneally) for two weeks, respectively, and were finally injected by Sco 30 min before Morris water maze test. The brains of animals were removed to determine the acetylcholinesterase (AChE) activity and oxidative stress criteria in cortical tissues.

RESULTSTime latency and path length in the Sco group were significantly higher than in the control group (P<0.01), while the Sco+NS 400 group showed a significantly shorter traveled path length and time latency compared with the Sco group (P<0.01). AChE activity in the cortical tissues of the Sco group was significantly higher than the control group (P<0.01), while AChE activity in the Sco+NS 200 and Sco+NS 400 groups was lower than the Sco group (P<0.01). Following Sco administration, malondialdehyde (MDA) concentrations were increased (P<0.01) in comparison with the control group, while cortical total thiol content decreased (P<0.01). Pretreatment with extracts caused a significant elevation in cortical total thiol content (P<0.01) and reduction in cortical MDA concentration (P<0.01) compared with the Sco group.

CONCLUSIONSHydro-alcoholic extract of NS prevents Sco-induced spatial memory deficits and decreases the AChE activity as well as oxidative stress of brain tissues in rats. Our results support the traditional belief about the beneficial effects of NS in nervous system. Moreover, further investigations are needed for better understanding of this protective effect.

Acetylcholinesterase ; metabolism ; Animals ; Ethanol ; chemistry ; Male ; Malondialdehyde ; metabolism ; Maze Learning ; drug effects ; Memory Disorders ; drug therapy ; physiopathology ; Nigella sativa ; chemistry ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Wistar ; Reaction Time ; drug effects ; Scopolamine Hydrobromide ; Spatial Memory ; drug effects ; Sulfhydryl Compounds ; metabolism ; Water ; chemistry

OBJECTIVETo study the mechanism of learning and memory dysfuction in the transgenic mouse expressing human tau 40 isoform with P301L mutation (F10).

METHODSThe human tau protein expression and phosphor-tau protein levels were detected with Western blot method. The neurofibrillary tangles were observed with Bielshowsky silver stain. The behavior changes of learning and memory were observed by open field test and passive avoidance test. Acetyleholine level, activities of acetycholinesterase and choline acetyltransferase of whole brain was detected by colorimetry method. The nitric oxide level of whole brain was detected by nitrate enzyme reduction method.

RESULTSExogenous human tau gene was expressed and an elevation of phosphor-tau protein level in 7 and 3-month transgenic mice's hippocampus andcerebrocortex was observed. The neurofibrillary tangles were observed in cerebrocortex of 7-month transgenic mice; the 7-month transgenic mice also presented an evident reduction of learning and memory ability and nitric oxide level of the whole brain, but not changes in acetylcholine level, acetycholinesterase activity, choline acetyltransferase activity and expression in whole brain.

CONCLUSIONTau transgenic mice (F10) can still inherit their parents' biologiccal characters, and develop learning and memory dysfunction awnodh san obvious decrease in nitric oxide level of whole brain in the 7-month old mice, suggesting a decrease of nitric oxide level of whole brain would be involved in the mechanism of learning and memory dysfunction in these transgenic mice.

Acetylcholine ; metabolism ; Acetylcholinesterase ; metabolism ; Animals ; Brain ; physiopathology ; Choline O-Acetyltransferase ; metabolism ; Humans ; Membrane Proteins ; genetics ; Memory Disorders ; genetics ; physiopathology ; Mice ; Mice, Transgenic ; Mutation ; Nitric Oxide ; metabolism

Recent studies showed that pathology of alcoholic encephalopathy was associated with cerebral vascular damage. TMP (tetramethyl- pyrazine) is widely used in the treatment of cerebrovascular diseases, however, it has not been reported whether TMP can relieve alcohol-induced cerebral vascular damages. The study was performed to investigate the learning and memory, cerebrovascular pathological changes and the expressions of vascular endothelial growth factor (VEGF) and serum levelsofendothelin-1 (ET-1) in the rat model of chronic alcoholic encephalopathy, and explore the effects of TMP intervention on alcoholic encephalopathy. In the present study, the rat model of chronic alcoholic encephalopathy was established by the gavage administration of alcohol; the learning and memory ability was tested by Morris water maze; the expression of VEGF was measured by RT-PCR and Western blot; and the serum levels of ET-1 was measured by radioimmunoassay. We found that alcohol intoxication impaired learning and memory, induced VEGF overexpression and increased ET 1 concentrations. TMP intervention improved learning abilities, increased the VEGF expression and reduced ET-1 level. These results indicate that TMP exhibits therapeutic effects on chronic alcoholic encephalopathy.
Alcohol-Induced Disorders, Nervous System ; complications ; drug therapy ; physiopathology ; Animals ; Cerebrovascular Circulation ; drug effects ; Disease Models, Animal ; Endothelin-1 ; blood ; Learning ; drug effects ; Male ; Memory ; drug effects ; Pyrazines ; pharmacology ; therapeutic use ; Random Allocation ; Rats ; Rats, Wistar ; Vascular Endothelial Growth Factor A ; analysis ; Vasodilator Agents ; pharmacology ; therapeutic use

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

OBJECTIVE: To research the serum levels of BDNF, H2S and S-100β as metabolic product of hippocampus and cerebral cortex in moderate to severe obstructive sleep apnea hypopnea syndrome(OSAHS) patients before and after surgery, and to analyze their correlations with cognitive impairment. METHOD: Forty-four randomly selected diagnosed OSAHS patients were divided into two groups according to Montreal Cognitive Assessment (MoCA), 19 cases in cognitively normal group and 25 cases in cognitive dysfunction group. Cases in cognitive dysfunction group underwent UPPP oriented surgery, and received 6 months follow-up, 21 cases were remained as treament group, 4 cases lost. 19 cases of healthy subjects were randomly selected as the normal control group. All groups were detected for the serum BDNF, H2S and S-100β levels to analyze the correlations between the biochemical indexes and sleep disorders indexes, hypoxia levels and cognitive function scores. RESULT: (1) In the comparison between the treatment group and the normal control group regarding PSG monitoring results, the AHI, I + II, LA/HT and SLT90% indexes of OSAHS patients increased, and the III + IV phase, REM phase, MSaO2 and LSaO2 decreased. In the comparison between the cognitive dysfunction group and the cognitively normal group, the III + IV, REM and LSaO2 indexes of the cognitive dysfunction group decreased. (2) In the comparison between cognitive dysfunction group and cognitively normal group, and between the treatment group and the normal control group, BDNF and H2S levels increased and S-100β levels decreased, and the MoCA total scores, attention, memory/delayed recall scores decreased. (3) The correlation between biochemical indexes with PSG indexes was as follows. The serum BNDF and H2S levels were negatively correlated with AHI index. The serum BNDF and H2S levels were positively correlated with III + IV stage, REM stage and MSaO2 indexes. The S-100β level was positively correlated with AHI index, and S-100β levels were negatively correlated with III + IV stage, REM stage, MSaO2 and LSaO2 indexes. (4) The correlation between biochemical indexes and MoCA scores was as follows. The serum BNDF and H2S levels were positively correlated with MoCA total scores, attention, and memory/delayed recall scores. The serum S-100β levels were negatively correlated with MoCA total scores, attention and memory/ delayed recall scores. (5) The linear regression equation between MoCA total scores in cognitive dysfunction group of OSAHS patients and the serum BNDF, H2S and S-100β levels was as follows: Y(MoCA) = 40.131 + 0.22 X(BDNF) + 0.012 X(H2S)-0.647X(S-100β) (R2 = 0.461). CONCLUSION OSAHS patients with sleep disorder and nocturnal hypoxemia might suffer from cognitive dysfunction in which attention and memory predominates. Serum BNDF, H2S and S-100β levels, which could indirectly reflect the metabolic abnormalities degree of hippocampus and cerebral cortex, are sensitive indicators of early cognitive dysfunction in OSAHS patients.
Brain-Derived Neurotrophic Factor ; metabolism ; Cerebral Cortex ; physiopathology ; Cognition Disorders ; complications ; Hippocampus ; physiopathology ; Humans ; Hypoxia ; Memory ; Metabolic Diseases ; physiopathology ; S100 Calcium Binding Protein beta Subunit ; metabolism ; Sleep Apnea, Obstructive ; complications

Qifu-Yin (QFY), a widely used formula of traditional Chinese medicine (TCM) derived from "Jingyue Quanshu", is one of the most commonly used TCM prescriptions for the clinical treatment of Alzheimer disease. The role of advanced glycation end products (AGEs) and its receptor RAGE have attracted increasing attention as the pivotal role of Aβ has been questioned. The present study was designed to test the neuroprotective effects of QFY, and the possible mechanism in AGE-induced Alzheimer model rats. After injection of AGE in the CA3 area of the hippocampus, QFY (8.6, 4.3, and 2.15 g·kg(-1)), and a positive control drug donepezil (2 mg·kg(-1)) were administrated through gastric intubation to rats once daily for thirty consecutive days. Another positive control group was the AGE + anti-RAGE group, which was simultaneously injected with anti-RAGE antibody before AGE treatment. The control group, sham-operated group, as well as the AGE + anti-RAGE group received saline at the same dosage. The Morris water maze test and the step-down passive avoidance test were conducted to evaluate the cognitive function of the rats. The expression of RAGE and NF-κB were assayed by immunohistochemical staining. The levels of Aβ, TNF-α, and IL-1β in the hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that QFY could significantly attenuate the memory impairment induced by AGE, decrease the expressions of RAGE and NF-κB, and reduce the levels of Aβ, TNF-α, and IL-1β in the hippocampus in a dose-dependent manner. Also, the blockage of RAGE could significantly reduce the impairments caused by AGEs. In conclusion, QFY could attenuate AGEs-induced, Alzheimer-like pathophysiological changes. These neuroprotective effects might be related to the RAGE/NF-κB pathway and its anti-inflammatory activity.
Alzheimer Disease ; drug therapy ; metabolism ; physiopathology ; Amyloid beta-Peptides ; metabolism ; Animals ; Anti-Inflammatory Agents ; pharmacology ; therapeutic use ; Brain ; drug effects ; metabolism ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Glycation End Products, Advanced ; adverse effects ; Interleukin-1beta ; metabolism ; Learning ; drug effects ; Magnoliopsida ; Male ; Memory Disorders ; drug therapy ; metabolism ; NF-kappa B ; metabolism ; Phytotherapy ; Plants, Medicinal ; Rats, Sprague-Dawley ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; metabolism ; Signal Transduction ; Tumor Necrosis Factor-alpha ; metabolism

Cognitive impairment in diabetes (CID) is a severe chronic complication of diabetes mellitus, and its pathogenesis has not yet been fully understood. Increasing evidence has shown that the distribution and expression of N-methyl-D-aspartame receptor (NMDAR) and subunits NR2A and NR2B, which all participated in the development of the central nervous system and formation of learning and memory, are correlated with the occurrence and development of CID.
Central Nervous System ; Cognition Disorders ; complications ; genetics ; Diabetes Mellitus ; physiopathology ; Humans ; Memory ; Receptors, N-Methyl-D-Aspartate ; metabolism

BACKGROUNDDepression related cognitive deficits are frequently considered as simple epiphenomena of the disorder. However, whether or not the depression might directly bring about cognitive deficits is still under investigation. This study was to investigate the distinct pattern of cognitive deficits in patients with depression by comparing the cognitive function before and after anti-depressive drug therapy.

METHODSSixty cases of patients, first-time diagnosed with depression, were assessed by 17-item Hamilton Rating Scale for Depression (HAMD17scale). The memory ability was tested by quantitatively clinical memory scale, while the attention ability by modified Ruff 2&7 Selective Attention Test. Forty-two healthy volunteers were recruited as controls. The depressive patients were treated with Venlafaxine (75 - 300 mg/d), Fluoxetine (20 - 40 mg/d), Paroxetine (20 - 40 mg/d), and Sertraline (50 - 150 mg/d). After 12 weeks treatment, patients were tested again by HAMD17scale, quantitatively clinical memory scale, and modified Ruff 2&7 selective attention test to assess the effect of anti-depressive drugs on cognitive deficits.

RESULTSThe memory quotient (MQ) was significantly lowered in depressive patients. The selection speed was also significantly decreased and the number of missing and error hits increased in the depression group as compared to control. However, there was no significant difference in clinical memory scale and Ruff 2&7 selective attention test between mild-to-moderate and severe depression group. Importantly, after anti-depressive drug therapy, the HAMD17 scale scores in depressive patients were significantly decreased, but the MQ, directional memory (DM), free recall (FR), associative learning (AL), and face recognition were comparable with those before the treatment. Furthermore, the selection speed and the number of missing and error hits were also not significantly different after anti-depressive drugs treatment.

CONCLUSIONSDepressive patients suffer from short-term memory deficits, and attention extent, stability and rearrangement deficiency. Even though anti-depressive drugs sufficiently relieve the cardinal presentation of depression, they could not successfully alleviate the accompanying cognitive deficits. This might indicate a distinct pattern of cognitive deficits in patients with depression.

Adolescent ; Adult ; Antidepressive Agents ; therapeutic use ; Cognition Disorders ; etiology ; physiopathology ; Depression ; complications ; drug therapy ; physiopathology ; Female ; Humans ; Male ; Memory ; drug effects ; physiology ; Middle Aged ; Neuropsychological Tests ; Young Adult