Effects of genistein on neuronal apoptosis,and expression of Bcl-2 and Bax proteins in the hippocampus of ovariectomized rats

Genistein is one of several isoflavones that has a structure similar to 17β-estradiol, has a strong antioxidant effect, and a high affinity to estrogen receptors. At 15 weeks after ovariectomy, the expression of Bcl-2 in the hippocampus of rats decreased and Bax expression increased, with an obvious upregulation of apoptosis. However, intraperitoneal injection of genistein or 17β-estradiol for 15 consecutive weeks from the second day after operation upregulated Bcl-2 protein expression downregulated Bax protein expression, and attenuated hippocampal neuron apoptosis. Our experimental findings indicate that long-term intervention with genistein can lead to a decrease in apoptosis in hippocampal neurons following ovadectomy, upregulate the expression of Bcl-2, and downregulate the expression of Bax. In addition, genistein and 17β-estradiol play equal anti-apoptotic and neuroprotective roles.

Effects of sericin on heme oxygenase-1 expression in the hippocampus and cerebral cortex of type 2 diabetes mellitus rats

Previous studies have demonstrated that sericin effectively reduces blood glucose, and protects islet cells, as well as the gonads and kidneys. However, whether sericin improves diabetes mellitus-induced structural and functional problems in the central nervous system remains poorly understood. Rat models of type 2 diabetes mellitus were established by intraperitoneal injection of streptozotocin. The present study observed histological changes in the hippocampus and cerebral cortex, as well as heme oxygenase-1 expression, and explored sericin effects on the central nervous system in diabetic rats. Pathological damage to neural cells in the rat hippocampus and cerebral cortex was relieved following intragastric administration of sericin at a dose of 2.4 g/kg for 35 consecutive days. Heme oxygenase-1 protein and mRNA expressions were decreased in the hippocampus and cerebral cortex of diabetes mellitus rats after sericin treatment. The results suggest that sericin plays a protective effect on the nervous system by decreasing the high expression of heme oxygenase-1 following diabetes mellitus.

Some of the experimental and clinical aspects of the effects of the maternal diabetes on developing hippocampus

Diabetes mellitus during pregnancy is associated with an increased risk of multiple congenital anomalies in progeny.There are sufficient evidence suggesting that the children of diabetic women exhibit intellectual and behavioral abnormalities accompanied by modification of hippocampus structure and function.Although,the exact mechanism by which maternal diabetes affects the developing hippocampus remains to be defined.Multiple biological alterations,including hyperglycemia,hyperinsulinemia,oxidative stress,hypoxia,and iron deficiency occur in pregnancies with diabetes and affect the development of central nervous system(CNS) of the fetus.The conclusion from several studies is that disturbance in glucose and insulin homeostasis in mothers and infants are major teratogenic factor in the development of CNS.Insulin and Insulin-like growth factor-1(IGF-1) are two key regulators of CNS function and development.Insulin and IGF-1 receptors(IR and IGF1 R,respectively) are distributed in a highly specific pattern with the high density in some brain regions such as hippocampus.Recent researches have clearly established that maternal diabetes disrupts the regulation of both IR and IGF1 R in the hippocampus of rat newborn.Dissecting out the mechanisms responsible for maternal diabetes-related changes in the development of hippocampus is helping to prevent from impaired cognitive and memory functions in offspring.

Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injury in rat hippocampus

Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both an-tioxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum （by intragastric administration） in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-a and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and an-tiinflammatory actions.

Studies on biological effect of lycopene on Hippocampus of hyperlipemia rats

Objective: This study investigated into the ef-fect of lycopene on expression of APP, bax and bcl-2 in hippocampal CA1 region of rats with hyperlipidemia. Methods: By total cholesterol (TC) and body weight, 48 adult male SD rats were randomized into six groups, a normal control group, fed with basic feed;a high-fat model group, fed with high-fat feed;a positive drug control group, fed with high-fat feed and administrated with fluvastatin sodium at a dose of 10 mg?kg?bw-1?d-1 by gastric perfusion;and lycopene groups at three dose levels, fed with high-fat feed and administrated with lycopene at doses of 11, 22 and 44 mg?kg?bw-1?d-1 respec-tively also by gastric perfusion. Caudal venous blood samples of rats in all groups were taken at week 0, week 1 and week 3 after the experiment started so as to assay TC, TG, LDL-C and HDL-C;at the end of the experiment, rat brains were taken and sections of the hippocampal CA1 re-gion were prepared. Expression of APP, bax and bcl-2 in the CA1 region was determined by im-munohistochemical methods and morphologi-cal examination was carried out. Results: One week after fed with high-fat feed, models of hy-perlipidemia rats were established;at the end of experiment, hippocampal APP and bax expres-sion was enhanced while bcl-2 expression was significantly weakened (p<0.05);to rats with hyperlipidemia, both lycopene and fluvastatin sodium could reduce TC, TG and LDL-C, inhibit expression of hippocampal APP and bax and promote expression of bcl-2 (p<0.05). Conclu- sion: Lycopene down-regulates the expression of bax and up-regulates that of bcl-2 mainly by reducing serum TC and LDL-C and weakening expression of APP in the hippocampal CA1 re-gion of rats with hyperlipidemia, thereby main-taining normal morphology of hippocampal neurons and facilitating the protection of the brain.

Effects of electroacupuncture on the expression of p70 ribosomal protein S6 kinase and ribosomal protein S6 in the hippocampus of rats with vascular dementia

This study investigated the mechanism underlying electroacupuncture therapy for vascular dementia through electroacupuncture at the acupoints of Baihui （DU20）, Dazhui （DU14）, and bilateral Shenshu （BL23） in a rat model of vascular dementia produced by bilateral middle cerebral artery occlusion. Morris water maze test showed that electroacupuncture improved the learning ability of vascular dementia rats. Western blot assay revealed that the expression of p70 ribosomal protein S6 kinase and ribosomal protein S6 in vascular dementia rats was significantly increased after electroacupuncture, compared with the model group that was not treated with acupuncture. The average escape latency was also shortened after electroacupuncture, and escape strategies in the spatial probe test improved from edge and random searches, to linear and trending swim pathways. The experimental findings indicate that electroacupuncture improves learning and memory ability by up-regulating expression of p70 ribosomal protein S6 kinase and ribosomal protein S6 in the hippocampus of vascular dementia rats.

Hypothyroid effects on astrocytes and microglia in the adult rat hippocampus

BACKGROUND： Thyroid hormones modulate proliferation of astrocytes and microglia depending on maturation stage and localization. Studies have demonstrated that triiodothyronine treatment or thyroidectomy during developmental stages results in morphological alterations and changes in the number of astrocytes and microglia. Little is known about the effects of hypothyroidism on astrocytes and microglia in adults. OBJECTIVE： To investigate the effects of hypothyroidism on morphology and number of astrocytes and microglia in the adult rat hippocampus. DESIGN, TIME AND SETTING： A randomized, controlled, neuroendocrinological, animal study was performed at the College of Medicine, Hallym University, South Korea between May 2008 and April 2009. MATERIALS： Methimazole, rabbit anti-glial fibrillary acidic protein （GFAP） antiserum, and rabbit anti-lba-1 antiserum were purchased from Sigma, USA. Rabbit anti-GFAP polyclonal antibody was provided by Chemicon, USA. Rabbit anti-lba-1 polyclonal antibody was purchased from Wako, Japan. Terminal deoxynucleotidyl transferase dUTP-biotin nick-end-labeling （TUNEL） kit was provided by Roche Molecular Biochemicals, Mannheim, Germany. METHODS： Hypothyroidism was induced in Wistar rats via methimazole administration （0.025%） in drinking water for 5 weeks, starting at 6 months of age. MAIN OUTCOME MEASURES： Following methimazole treatment, hippocampai neuronal death was determined using TUNEL staining. The morphology and number of GFAP and lba-1 immunoreactive cells were detected by immunohistochemistry. Hippocampal GFAP and lba-1 protein levels were detected by Western blot analysis. Serum-free triiodothyronine and thyroxine levels were quantified. RESULTS： TUNEL-positive neurons were not observed in the hippocampus of euthyroid and hypothyroid rats. Compared with the euthyroid rats, the number of GFAP immunoreactive astrocytes was decreased, and serum triiodothyronine and thyroxine levels were significantly decreased. In contrast, the number of lba-1 immunoreactive microglia was significantly increased in the hypothyroid rats （P 〈 0.05）. In addition, GFAP immunoreactive astrocytes were morphologically at a resting state, and lba-1 immunoreactive microglia were morphologically hypertrophic. GFAP and IBa-1 protein changes in the hippocampus of euthyroid and hypothyroid rats were in accordance with immunohistochemical data. CONCLUSION： Although methimazole-induced hypothyroidism did not induce neuronal injury in the adult rat hippocampus, it did result in decreased astrocyte numbers and increased microglial hypertrophy.

Effect of agonist on gamma-aminobutyric acid B receptor subunit expression in the hippocampus of epileptic rats

BACKGROUND： An amino acid imbalance has been considered to be responsible for epilepsy pathogenesis. Gamma-aminobutyric acid-B receptor （GABABR） inhibits voltage-sensitive calcium ion channels and GABA or glutamic acid （Glu） neurotransmitter release, which promotes or inhibits onset and development of epilepsy. OBJECTIVE： To explore the effect of baclofen on GBRla and GBR2 mRNA expression in the hippocampus of epileptic rats following kainic acid （KA） induction, and to study the adaptability of GABABR subunits. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment based on molecular biology was performed at the Laboratory Research Center of Second Hospital Affiliated to Soochow University from November 2005 to March 2006. MATERIALS： KA was provided by Sigma, USA. In situ hybridization detection kit of GBRla and GBR2 was provided by Wuhan Boster Biological Technology, China. GABABR agonist （baclofen） was provided by Sigma, USA. METHODS： Forty-four epileptic rats were randomly allocated to epileptic （n = 28） and drug intervention （n = 16） groups. The epileptic group was further divided into post-epileptic subgroups at different time points： 6, 12 hours, 1, 3, 7, 15, and 30 days （n = 4）. The drug intervention group was further divided into intervention controls subgroups at various time points： 6 hours, 1 day, and 3 days （n = 4）. Four additional rats were considered the normal control group and not modeled, but were injected with saline in the hippocampal CA3 region. MAIN OUTCOME MEASURES： GBRla and GBR mRNA expression was detected in the right hippocampal CA1, CA3, and dentate gyrus （DG） areas of the control, epileptic, and interference groups at various time intervals according to in situ hybridization results. RESULTS： （1） During the early stage of epilepsy （6 and 12 hours）, GBRla and GBR2 mRNA expression was decreased, and expression was less than the control group at one day after KA induction （P 〈 0.05）. mRNA expression was increased in the DG, but was greater than the control group at day 3 （P 〈 0.05）. Expression in the hippocampal CA1 and CA3 regions remained low （P 〈 0.05）, but gradually recovered to control levels. （2） The time points when subunit expression was decreased were prolonged following baclofen intervention, and expression was significantly greater than the epileptic group （P 〈 0.05）. CONCLUSION： Both mRNA expressions of GABABR subunits were up-regulated following decreased expression in the epileptic group, suggesting that the temporal lobe exhibited endogenous antiepileptic mechanisms during the early stages of epilepsy onset. Baclofen promoted mRNA expression of GBRla and GBR2.

Effect of electroacupuncture on glial fibrillary acidic protein and nerve growth factor in the hippocampus of rats with hyperlipidemia and middle cerebral artery thrombus

Electroacupuncture(EA)has been shown to reduce blood lipid level and improve cerebral ischemia in rats with hyperlipemia complicated by cerebral ischemia.However,there are few studies on the results and mechanism of the effect of EA in reducing blood lipid level or promoting neural repair after stroke in hyperlipidemic subjects.In this study,EA was applied to a rat model of hyperlipidemia and middle cerebral artery thrombosis and the condition of neurons and astrocytes after hippocampal injury was assessed.Except for the normal group,rats in other groups were fed a high-fat diet throughout the whole experiment.Hyperlipidemia models were established in rats fed a high-fat diet for 6 weeks.Middle cerebral artery thrombus models were induced by pasting 50%FeCl3 filter paper on the left middle cerebral artery for 20 minutes on day 50 as the model group.EA1 group rats received EA at bilateral ST40(Fenglong)for 7 days before the thrombosis.Rats in the EA1 and EA2 groups received EA at GV20(Baihui)and bilateral ST40 for 14 days after model establishment.Neuronal health was assessed by hematoxylin-eosin staining in the brain.Hyperlipidemia was assessed by biochemical methods that measured total cholesterol,triglyceride,low-density lipoprotein and high-density lipoprotein in blood sera.Behavioral analysis was used to confirm the establishment of the model.Immunohistochemical methods were used to detect the expression of glial fibrillary acidic protein and nerve growth factor in the hippocampal CA1 region.The results demonstrated that,compared with the model group,blood lipid levels significantly decreased,glial fibrillary acidic protein immunoreactivity was significantly weakened and nerve growth factor immunoreactivity was significantly enhanced in the EA1 and EA2 groups.The repair effect was superior in the EA1 group than in the EA2 group.These findings confirm that EA can reduce blood lipid,inhibit glial fibrillary acidic protein expression and promote nerve growth factor expression in the hippocampal CA1 region after hyperlipidemia and middle cerebral artery thrombosis.All experimental procedures and protocols were approved by the Animal Use and Management Committee of Beijing University of Chinese Medicine,China(approval No.BUCM-3-2018022802-1002)on April 12,2018.

Similar effects of substance P on learning and memory function between hippocampus and striatal marginal division

Substance P is an endogenous neurokinin that is present in the central and peripheral nervous systems. The neuropeptide substance P and its high-affinity receptor neurokinin 1 receptor are known to play an important role in the central nervous system in inflammation, blood pressure, motor behavior and anxiety. The effects of substance P in the hippocampus and the marginal di- vision of the striatum on memory remain poorly understood. Compared with the hippocampus as a control, immunofluorescence showed high expression of the substance P receptor, neuro- kinin 1, in the marginal division of the striatum of normal rats. Unilateral or bilateral injection of an antisense oligonucleotide against neurokinin 1 receptor mRNA in the rat hippocampus or marginal division of the striatum effectively reduced neurokinin 1 receptor expression. Indepen- dent of injection site, rats that received this antisense oligonucleotide showed obviously increased footshock times in a Y-maze test. These results indicate that the marginal division of the striatum plays a similar function in learning and memory to the hippocampus, which is a valuable addi- tion to our mechanistic understanding of the learning and memory functions of the marginal division of the striatum.

Combined effects of electroacupuncture and anti-depression drugs on the hippocampus and frontal lobe

Electroacupuncture （EA） has been clinically used to treat depression and has resulted in favorable effects in China. However, results from animal studies and pathology do not reflect the influence of electroacupuncture treatment on in vivo physiological functions. To thoroughly and dynamically observe pathological changes during depression, the present study established EA ＋ fluoxetine and fluoxetine groups to observe depression in patients. 1H-magnetic resonance spectroscopy was utilized to determine the correlation between hippocampal frontal lobe metabolite changes and mental disorder scale. Results revealed significantly increased N-acetylaspartate （NAA）/creatine （Cr） in the bilateral hippocampus and right frontal lobe of depression patients treated with EA compared with fluoxetine. Changes in NAA/Cr in bilateral hippocampus and right frontal lobe in both groups, before and after treatment, negatively correlated with severity and curative effects. Choline/Cr changes in the bilateral frontal lobes of both groups were significant before and after treatment, but negatively correlated with curative effects. Choline/Cr changes in the bilateral hippocampus were significant in the EA ＋ fluoxetine group before and after treatment, but negatively correlated with severity and the curative effects of depression. These results demonstrate abnormal biochemical metabolism in bilateral frontal lobes and hippocampus of depression patients, and show that EA significantly altered biochemical indices in the frontal lobes and hippocampus compared with fluoxetine.

Effect of midazolam on the proliferation of neural stem cells isolated from rat hippocampus

In many recent studies, the inhibitory transmitter gamma-aminobutyric acid has been shown to modulate the proliferation, differentiation and survival of neural stem cells. Most general anesthetics are partial or allosteric gamma-aminobutyric acid A receptor agonists, suggesting that general anesthetics could alter the behavior of neural stem cells. The neuroprotective efficacy of general anesthetics has been recognized for decades, but their effects on the proliferation of neural stem cells have received little attention. This study investigated the potential effect of midazolam, an extensively used general anesthetic and allosteric gamma-aminobutyric acid A receptor agonist, on the proliferation of neural stem cells in vitro and preliminarily explored the underlying mechanism. The proliferation of neural stem cells was tested using both Cell Counting Kit 8 and bromodeoxyuridine incorporation experiments. Cell distribution analysis was performed to describe changes in the cell cycle distribution in response to midazolam. Calcium imaging was employed to explore the molecular signaling pathways activated by midazolam. Midazolam （30-90 IJM） decreased the proliferation of neural stem cells in vitro. Pretreatment with the gamma-aminobutyric acid A receptor antagonist bicuculline or Na-K-2CI cotransport inhibitor furosemide partially rescued this inhibition. In addition, midazolam triggered a calcium influx into neural stem cells. The suppressive effect of midazolam on the proliferation of neural stem cells can be partly attributed to the activation of gamma-aminobutyric acid A receptor. The calcium influx triggered by midazolam may be a trigger factor leading to further downstream events.

Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resilience in Tg2576 mice.

Apomorphine effects on the hippocampus

Apomorphine is a non-specific dopamine receptor agonist that has been used in the treatment of some diseases and mental disorders. Its use has particularly well documented in Parkinson＇s disease（PD）. The dopaminergic agonists like apomorphine are related to oxidative processes that could induce cell damage and the functional impairment of some structures in the brain. However, most information about apomorphine in literature is focused on the improvement of the motor problems characteristic of PD, but little is known about the effects on cognitive behaviors and brain structures indirectly related to motor function. The presence of dopaminergic receptors in the hippocampus has recently been discovered, in connection with cognitive behaviors like learning and memory, these receptors are needed in neuronal plasticity. There has been a growing interest to know if this structure could be compromised by the effect of apomorphine and elucidate if part of the cognitive impairment present in the PD is due to the effect of apomorphine. In this mini-review, we summarized how apomorphine has been used since its creation, we discuss the latest information about its effect on the hippocampus and also the future perspectives to fully understand the effects of this compound.

Molecular mechanisms of seasonal photoperiod effects of the pineal gland on the hippocampus in rats

Background:Based on the theory of“five Zang-organs corresponding to the seasons”in traditional Chinese medicine(TCM),physiological functions including emotions vary with the seasons.We aimed to investigate the seasonal photoperiod effects of melatonin(MT)released from the pineal gland on the MT receptor(MTR)-Gs/Gi-cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)-cAMP response element-binding protein(CREB)signaling pathway in the hippocampus.Methods:Rats were divided into three groups:control,operation(surgery with pineal gland removal),and pseudo-operation groups(same surgery as operation group but without removing pineal gland),and fed at specific time across the four seasons.The levels of MTR,adenylate cyclase(AC),cAMP,PKA,and CREB in the hippocampus were analyzed using ELISA.The concentrations of Gs and Gi were analyzed using Western blot.The expression of CREB mRNA was detected by PCR.Results:For intragroup comparisons,compared with spring,the levels of Gs/Gi in the control group were higher in summer,autumn,and winter(P=.009 in summer;P<.001 in autumn and winter);the levels of MTR,cAMP,PKA,and CREB in the control group were significantly higher in autumn and winter than in spring(all P<.001).The levels of MTR,cAMP,PKA,and CREB in each season were significantly lower in the operation group than in the control group(all P<.05).Significant differences were noted in Gs/Gi levels between the operation group and control group in spring,autumn,and winter(all P<.05).Conclusion:Our findings suggest that MTR-Gs/Gi-cAMP-PKA-CREB signaling pathway is involved in the seasonal photoperiod effects of the pineal gland on the hippocampus and may underpin seasonal changes in emotions.It can support the prevention and treatment of the seasonal onset of mental disorders,and enrich the theory of“five Zang-organs corresponding to the seasons”.

Protective effect of neurotrophin-3 secreting myoblasts against kainic acid-induced exitotoxic lesions in rat hippocampus

Neurotrophic factors are able to promote neuronalsurvival and prevent neuronal death induced by variousinjuries and have potential uses in the treatment ofneuronal degenerative diseases and neuropathy. Due tothe existence of brain blood barrier, neurotrophic factorscan not be ased in CNS diseases directly. Gene therapy isa good candidate to overcome this problem.

EVALUATION OF NEUROPROTECTIVE EFFECTS OF LONG-TERM LOW DOSE HORMONE REPLACEMENT THERAPY ON POSTMENOPAUSAL WO-MEN BRAIN HIPPOCAMPUS USING MAGNETIC RESONANCE SCANNER

To investigate the effects of long-term low dose hormone replacement therapy （HRT） on postmenopaosal women in homone level, cognition score, hippocampus volume, and magnetic resonance spectroscopy （MRS） parameters. Methods A total of 182 postmenopausal women aged 50-87 years were chosen at Peking Union Medical College Hospital and assigned to HRT group and control group. The volunteers of HRT group had taken low dose hormone [ estradiol （E2 ） 0. 5-1.0 mg and progesterone 0.5-2.0 mg, once a day ] for 4-33 years. The concentrations of E2, progesterone, and testosterone were measured using enzyme-linked immunosorbent assay （ELISA）. The gene types of apolipoprotein E （ApoE） were measured by polymerase chain reaction, and the subjects with susceptible genes （ ApoE ε3/ε4） of Alzheimer＇s disease （AD） were screened. Their hippocampus volumes and MRS parameters were obtained through magnetic resonance imaging （MRI）, and results in two groups were analyzed by statistical method. Results Compared with control group, the concentrations of E2 at each age stage in HRT group were significantly higher （P 〈0. 05） except the 80-89 years old subgroup; yet, there were no statistical differences in the concentrations of progesterone and testosterone between the two groups. There was no obvious difference in ApoE subtypes distribution between the two groups The results of hippocampus MRI for the subjects with susceptible genes ApoE ε3/ε4 （HRT group 14 cases, control group 11 cases） showed that the ratio of bilateral hippocampus volume to whole brain volume in HRT group （0. 406 ± 0.028） was signiticantlyhigher than control gronp （0.369±0.031, P〈0.05）. Theresults of ^1H MRS for the subjects with susceptible genes ApoE ε3/ε4 （ HRT group 12 cases, control group 11 cases） showed that the N-acetylaspartate/total creatine at the area of hippocampus in HRT group （ 1.54±0. 08 ） were significantly higher than control group （ 1.45±0. 13, P 〈 0. 05）. Conclusions For postmenopausal women, long-term low dose HRT can maintain the physiological concentration of E2 in plasma. Furthermore, the hippocampus MRI performed on those with ApoE ε3/ε3 genes shows that long-term low dose HRT can prevent hippocampus atrophy, which is beneficial to maintain the brain function and prevent AD.

Neurotropic effects of aspartame, stevia and sucralose on memory retention and on the histology of the hippocampus of the ICR mice(Mus musculus)

Objective: To identify the effects of the consumption of non-nutritive sweeteners on memory retention and on the histology of the hippocampus.Methods: In this study, 20 mice were used to determine if there is an effect of consuming the maximum allowable dose of the non-nutritive sweeteners on the memory retention and on the histology of the hippocampus. The mice were distributed into four groups and the treatments were given via oral gavage: Group 1(water), Group 2(aspartame: 1 000 mg/kg), Group 3(stevia: 1 000 mg/kg) and Group 4(sucralose:16 000 mg/kg). Treatments were administered to the different experimental groups for 32 days, after which memory retention was tested using the two-day water maze protocol.After the tests, the mice were sacrificed and the brain was analyzed histologically for neurotrophic effects.Results: Based on the results of the two-day water maze protocol, there were no differences between the non-nutritive sweeteners and the control group. However, stevia showed high cellular apoptosis followed by aspartame, sucralose and control group.Conclusions: There was no significant effect on the memory of the mice. It showed histologically however, that stevia had a significant neurotropic effect compared to the other sweeteners.

Effect of Dexamethasone on Glu-IR and GABA-IR Neuronsof Hippocampus in Rats

Dexamethasone (Dex) was injected into the rat lateral ventricle and the changes of glutamate-imrnunoreactivity (Glu-IR ) and Y-aminobulyric acid immunoreactivity (GABA-IR ) neurons in the hippocampus were immunocytochemically examined 2 h after injection. The resu1ts showed that Glu-IR neurons increased and GABA-IR neurons did not show marked change. The mechanism remains to be further studied.

Effect of [Ca^(2+)]_i and Neuronal Mitochondria Transmembrane Potentials in Hippocampus of Murine Cytomegalovirus Infected Mice

To explore the effect of [-Ca^2＋]i and neuronal mitochondria transmembrane potentials in hippocampus of murine cytomegalovirus （MCMV） infected mice, newborn Balb/c mice were randomly divided into two groups： a virus inoculated group and a control group. After 56 days, single cell of hippocampus was isolated, and mitochondria transmembrane potentials and the intracellular free calcium level [-Ca^2＋]i in hippocampus were measured by means of flow cytometry （FCM）. Compared with the control group, the mitochondria transmembrane potentials was decreased （P〈0. 01 ） and the intracellular free calcium level [-Ca^2＋]i was increased （P〈0. 01） in inoculated group. The dysfunction of [-Ca^2＋]i and mitochondria transmembrane potentials in hippocampus may play an important role in the functional disorders in CMV-infected CNS.