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.

Do tau-synaptic long-term depression interactions in the hippocampus play a pivotal role in the progression of Alzheimer’s disease?

Cognitive decline in Alzheimer’s disease correlates with the extent of tau pathology,in particular tau hyperphosphorylation that initially appears in the transentorhinal and related regions of the brain including the hippocampus.Recent evidence indicates that tau hyperphosphorylation caused by either amyloid-βor long-term depression,a form of synaptic weakening involved in learning and memory,share similar mechanisms.Studies from our group and others demonstrate that long-term depression-inducing low-frequency stimulation triggers tau phosphorylation at different residues in the hippocampus under different experimental conditions including aging.Conversely,certain forms of long-term depression at hippocampal glutamatergic synapses require endogenous tau,in particular,phosphorylation at residue Ser396.Elucidating the exact mechanisms of interaction between tau and long-term depression may help our understanding of the physiological and pathological functions of tau/tau(hyper)phosphorylation.We first summarize experimental evidence regarding tau-long-term depression interactions,followed by a discussion of possible mechanisms by which this interplay may influence the pathogenesis of Alzheimer’s disease.Finally,we conclude with some thoughts and perspectives on future research about these interactions.

Quantitative proteomic and phosphoproteomic analyses of the hippocampus reveal the involvement of NMDAR1 signaling in repetitive mild traumatic brain injury

The cumulative damage caused by repetitive mild traumatic brain injury can cause long-term neurodegeneration leading to cognitive impairment.This cognitive impairment is thought to result specifically from damage to the hippocampus.In this study,we detected cognitive impairment in mice 6 weeks after repetitive mild traumatic brain injury using the novel object recognition test and the Morris water maze test.Immunofluorescence staining showed that p-tau expression was increased in the hippocampus after repetitive mild traumatic brain injury.Golgi staining showed a significant decrease in the total density of neuronal dendritic spines in the hippocampus,as well as in the density of mature dendritic spines.To investigate the specific molecular mechanisms underlying cognitive impairment due to hippocampal damage,we performed proteomic and phosphoproteomic analyses of the hippocampus with and without repetitive mild traumatic brain injury.The differentially expressed proteins were mainly enriched in inflammation,immunity,and coagulation,suggesting that non-neuronal cells are involved in the pathological changes that occur in the hippocampus in the chronic stage after repetitive mild traumatic brain injury.In contrast,differentially expressed phosphorylated proteins were mainly enriched in pathways related to neuronal function and structure,which is more consistent with neurodegeneration.We identified N-methyl-D-aspartate receptor 1 as a hub molecule involved in the response to repetitive mild traumatic brain injury,and western blotting showed that,while N-methyl-D-aspartate receptor 1 expression was not altered in the hippocampus after repetitive mild traumatic brain injury,its phosphorylation level was significantly increased,which is consistent with the omics results.Administration of GRP78608,an N-methyl-D-aspartate receptor 1 antagonist,to the hippocampus markedly improved repetitive mild traumatic brain injury-induced cognitive impairment.In conclusion,our findings suggest that N-methyl-D-aspartate receptor 1 signaling in the hippocampus is involved in cognitive impairment in the chronic stage after repetitive mild traumatic brain injury and may be a potential target for intervention and treatment.

SC-Net:A New U-Net Network for Hippocampus Segmentation

Neurological disorders like Alzheimer’s disease have a significant impact on the lives and health of the elderly as the aging population con-tinues to grow.Doctors can achieve effective prevention and treatment of Alzheimer’s disease according to the morphological volume of hippocam-pus.General segmentation techniques frequently fail to produce satisfactory results due to hippocampus’s small size,complex structure,and fuzzy edges.We develop a new SC-Net model using complete brain MRI images to achieve high-precision segmentation of hippocampal structures.The proposed network improves the accuracy of hippocampal structural segmentation by retaining the original location information of the hippocampus.Extensive experimental results demonstrate that the proposed SC-Net model is signif-icantly better than other models,and reaches a Dice similarity coefficient of 0.885 on Alzheimer’s Disease Neuroimaging Initiative(ADNI)dataset.

温度突变对大海马(Hippocampus kuda)幼体生长、组分及酶活力的影响

以大海马幼体为实验材料,通过设置不同的温度突变组(温度从23℃突变至15℃、28℃和33℃)的方法,对其生长、生化组分以及酶活力的影响进行了研究。结果表明,实验结束后,28℃温度组的大海马幼体生长指标、蛋白含量、能值显著高于23℃对照组(P<0.05),而15℃、33℃温度组的各项指标则显著低于对照组(P<0.05);此外,温度突变组的大海马幼体的酶活力均有先升后降的趋势,在1d后出现峰值,4—6d各个温度组趋于稳定,到实验第15天时,28℃温度组的SOD、ACP活力和MDA的含量已处于23℃对照组水平(P>0.05),CAT、AKP活力显著高于23℃对照组(P<0.05)。而15℃、33℃温度组的SOD、CAT活力降至低于23℃对照组水平(P<0.05),15℃温度组的ACP、AKP活力则低于23℃对照组水平(P<0.05),MDA的含量在15℃、33℃温度组随时间延长而增加。

盐度胁迫对大海马(Hippocampus kuda)幼体生长、组分及酶活力的影响

在盐度为25的条件下,以大海马幼体为实验材料,通过设置不同的盐度胁迫组(盐度从25胁迫至5、15和35)的方法,对其生长、生化组分以及酶活力的影响进行了研究。结果表明:15盐度组大海马幼体的体重、生化组分、能值与对照组(盐度25)相比差异不显著(P>0.05),体长、成活率指标则显著高于对照组(P<0.05),然而5、35盐度组的生长指标、成活率、生化组分等则显著低于对照组(P<0.05)。15盐度组的SOD、CAT酶活性低于对照组水平(P<0.05),MDA的含量变化不显著(P>0.05);而5、35盐度组SOD、CAT和MDA含量与对照组相比,随着时间的延长,呈现逐渐升高的趋势(P<0.05);随着盐度的升高,AKP酶活性具有逐渐升高的趋势,而ACP酶活性则呈现降低趋势。

Microinjection of M_5 muscarinic receptor antisense oligonucleotide into VTA inhibits FosB expression in the NAc and the hippocampus of heroin sensitized rats

Objective To investigate the effect of M5 muscarinic receptor subtype on the locomotor sensitization induced by heroin priming, and it＇s effect on the FosB expression in the nucleus accumbens （NAc） and the hippocampus in the heroin sensitized rats. Methods Locomotor activity was measured every 10 min for 1 h after subcutaneous injection of heroin. FosB expression was assayed by immunohistochemistry, and the antisense oligonucleotides （AS-ONs） targeting M5 muscarinic receptor was transferred with the lipofectin. Results Microinjection of AS-ONs targeting M5 muscarinic receptor in the ventral tegmental area （VTA） blocked the expression of behavioral sensitization induced by heroin priming in rats. Meanwhile, the expression of FosB-positive neurons in either the NAc or the dentate gyrus （DG） of the hippocam- pus increased in heroin-induced locomotor sensitized rats. The enhancement of FosB-positive neurons in the NAc or DG could be inhibited by microinjection of M5 muscarinic receptor AS-ONs into the VTA before the heroin-induced locomotor sensitization was performed. In contrast, microinjection of M5 muscarinic receptor sense oligonucleotide （S-ONs） into the VTA did not block the expression of behavioral sensitization or the expression of FosB in the NAc or DG in the heroin sensitized rats. Conclusion Blocking M5 muscarinic receptor in the VTA inhibits the expression of heroin-induced locomotor sensitization, which is associated with the regulation of FosB expression in the NAc and hippocampus neurons. M5 muscarinic receptor may be a useful pharmacological target for the treatment of heroin addiction.

Cytochrome P450 Directed Prodrug Activation Therapy in Research of Cancer Enzymology

Cancer enzymology is a promising filiation of bio-medical sciences. In thepast decades, enzymes, such as GST(glutathione S-transferase) , PKC(protein kinase C) , Topo(DNAtopoisomerases), TK(tyrosine kinase), CD (bacterial cytosine deaminase), CPG2(carboxypeptidase G2) ,and PNP (purine nucleoside phosphorylase), have been known to bear close relations to cancer. Theirspecific expression and influence on the process of tumor initiation, promotion and progressionattract scientists to apply them as a biochemical marker of certain malignant tumor, a predictor ofresponse in cancer chemotherapy; to apply them to drug design, tumor prevention and as adjuvant toradiotherapy or surgery.

线纹海马(Hippocampus erectus)性腺特异性结构与生殖细胞发育特征研究

海马属(Hippocampus)鱼类具有独特的雄性育儿繁殖方式,其卵巢和精巢结构也极其独特。本研究系统阐明了线纹海马(Hippocampuserectus)的性腺及生殖细胞的发育特征,根据组织学结构和细胞形态学变化特征,将线纹海马的精巢和卵巢发育过程均分为6个时期。其中,卵巢发育方式为不同步成熟型,Ⅰ期卵巢只包含第Ⅰ时相卵母细胞,包括卵原细胞和早期初级卵母细胞(d<20μm);Ⅱ期卵巢开始出现第Ⅱ时相卵母细胞(d=20~140μm);Ⅲ期卵巢卵母细胞数量显著增多,体积增大,并开始出现第Ⅲ时相卵母细胞(d=140~260μm),此时细胞内开始出现皮质小泡、卵黄颗粒和卵黄膜;Ⅳ期卵巢开始出现第Ⅳ时相卵母细胞(d=260~1100μm),卵黄颗粒充满整个细胞质,形成过渡期的卵黄球;Ⅴ期卵巢出现大量第Ⅴ时相成熟卵母细胞(d=1100~2000μm),细胞内形成流动性卵黄囊;Ⅵ期卵巢为排卵不久后的卵巢,卵母细胞数量显著减少。线纹海马精巢属于非限制型小叶精巢,Ⅰ期精巢主要含精原细胞,核大,含一到多个核仁;Ⅱ期精巢开始形成精小囊,囊内出现初级精母细胞;Ⅲ期精巢呈乳白色,开始出现次级精母细胞;Ⅳ期精巢体积较Ⅲ期时显著增大,开始出现精子细胞,并逐渐移向中央生精腔;Ⅴ期精巢内含大量的成熟精子,随时准备释放。精子释放后精巢进入Ⅵ期,残留少量精细胞在生精腔中。组织化学反应结果显示,氨基酸、蛋白质和脂肪的信号在卵母细胞的细胞质、卵黄囊中呈阳性,且随着卵母细胞的发育而增强。本研究结果为进一步探索海马属鱼类雄性繁殖策略提供了重要的基础数据。

Relationship between Cognition Function and Hippocampus Structure after Long-term Microwave Exposure

Objective To analyze the effects of long-term microwave exposure on hippocampal structure and function in the rat.Methods Experiments were performed on 184 male Wistar rats（three exposure groups and a sham group）.Microwaves were applied daily for 6 min over 1 month at average power densities of 2.5,5,and 10 mW/cm2.Learning and memory abilities were assessed by Morris water maze.High performance liquid chromatography was used to detect neurotransmitter concentrations in the hippocampus.Hippocampal structures were observed by histopathological analysis.Results Following long-term microwave exposure there was a significant decrease in learning and memory activity in the 7 d,14 d,and 1 m in all three microwave exposure groups.Neurotransmitter concentrations of four amino acids（glutamate,aspartic acid,glycine,and gamma-aminobutyric acid） in hippocampus were increased in the 2.5 and 5 mW/cm2 groups and decreased in the 10 mW/cm2 group.There was evidence of neuronal degeneration and enlarged perivascular spaces in the hippocampus in the microwave exposure groups.Further,mitochondria became swollen and cristae were disordered.The rough endoplasmic reticulum exhibited sacculated distension and there was a decrease in the quantity of synaptic vesicles.Conclusion These data suggest that the hippocampus can be injured by long-term microwave exposure,which might result in impairment of cognitive function due to neurotransmitter disruption.

Microwave Exposure Impairs Synaptic Plasticity in the Rat Hippocampus and PC12 Cells through Over-activation of the NMDA Receptor Signaling Pathway

Objective The aim of this study is to investigate whether microwave exposure would affect the N-methyI-D-aspartate receptor （NMDAR） signaling pathway to establish whether this plays a role in synaptic plasticity impairment. Methods 48 male Wistar rats were exposed to 30 mW/cm^2 microwave for 10 min every other day for three times. Hippocampal structure was observed through H＆E staining and transmission electron microscope. PC12 cells were exposed to 30 mW/cm^2 microwave for 5 min and the synapse morphology was visualized with scanning electron microscope and atomic force microscope. The release of amino acid neurotransmitters and calcium influx were detected. The expressions of several key NMDAR signaling molecules were evaluated. Results Microwave exposure caused injury in rat hippocampal structure and PC12 cells, especially the structure and quantity of synapses. The ratio of glutamic acid and gamma-aminobutyric acid neurotransmitters was increased and the intracellular calcium level was elevated in PC12 cells. A significant change in NMDAR subunits （NR1, NR2A, and NR2B） and related signaling molecules （CaZ＋/calmodulin-dependent kinase II gamma and phosphorylated cAMP-response element binding protein） were examined. Conclusion 30 mW/cm^2 microwave exposure resulted in alterations of synaptic structure, amino acid neurotransmitter release and calcium influx. NMDAR signaling molecules were closely associated with impaired synaptic plasticity.

Behavioral Abnormality along with NMDAR-related CREB Suppression in Rat Hippocampus after Shortwave Exposure

Objective To estimate the detrimental effects of shortwave exposure on rat hippocampal structure and function and explore the underlying mechanisms. Methods One hundred Wistar rats were randomly divided into four groups(25 rats per group) and exposed to 27 MHz continuous shortwave at a power density of 5, 10, or 30 m W/cm^2 for 6 min once only or underwent sham exposure for the control. The spatial learning and memory, electroencephalogram(EEG), hippocampal structure and Nissl bodies were analysed. Furthermore, the expressions of N-methyl-D-aspartate receptor(NMDAR) subunits(NR1, NR2 A, and NR2 B), c AMP responsive element-binding protein(CREB) and phosphorylated CREB(p-CREB) in hippocampal tissue were analysed on 1, 7, and 14 days after exposure. Results The rats in the 10 and 30 m W/cm^2 groups had poor learning and memory, disrupted EEG oscillations, and injured hippocampal structures, including hippocampal neurons degeneration, mitochondria cavitation and blood capillaries swelling. The Nissl body content was also reduced in the exposure groups. Moreover, the hippocampal tissue in the 30 m W/cm^2 group had increased expressions of NR2 A and NR2 B and decreased levels of CREB and p-CREB. Conclusion Shortwave exposure(27 MHz, with an average power density of 10 and 30 m W/cm^2) impaired rats' spatial learning and memory and caused a series of dose-dependent pathophysiological changes. Moreover, NMDAR-related CREB pathway suppression might be involved in shortwave-induced structural and functional impairments in the rat hippocampus.

Ulinastatin suppresses endoplasmic reticulum stress and apoptosis in the hippocampus of rats with acute paraquat poisoning

Lung injury is the main manifestation of paraquat poisoning. Few studies have addressed brain damage after paraquat poisoning. Ulinastatin is a protease inhibitor that can effectively stabilize lysosomal membranes, prevent cell damage, and reduce the production of free radicals. This study assumed that ulinastatin would exert these effects on brain tissues that had been poisoned with paraquat. Rat models of paraquat poisoning were intraperitoneally injected with ulinastatin. Simultaneously, rats in the control group were administered normal saline. Hematoxylin-eosin staining showed that most hippocampal cells were contracted and nucleoli had disappeared in the paraquat group. Fewer cells in the hippocampus were concentrated and nucleoli had dis- appeared in the ulinastatin group. Western blot assay showed that expressions of GRP78 and cleaved-caspase-3 were significantly lower in the ulinastatin group than in the paraquat group. Immunohistochemical findings showed that CHOP immunoreactivity was significantly lower in the ulinastatin group than in the paraquat group. Terminal deoxynucleotidyl transferase-medi- ated dUTP nick end labeling staining showed that the number of apoptotic cells was reduced in the paraquat and ulinastatin groups. These data confirmed that endoplasmic reticular stress can be induced by acute paraqnat poisoning. Ulinastatin can effectively inhibit this stress as well as cell apoptosis, thereby exerting a neuroprotective effect.

Study of the hippocampus and the anterior cingulate gyrus by proton MR spectroscopy in patients with post-traumatic stress disorder

Objective:To explore the characteristics of metabolic changes in patients with post-traumatic stress disorder through 1H-MRS in neuroanatomical circuit comparing with age-matches controls.Methods:Fifty patients with post-traumatic stress disorder and SO gender-and agematched normal controls were involved.The neurochemical abnormalities including the levels of choline(Cho)/ creatine(Cr) and N-acetylaspartate(NAA)/Cr were measured respectively in hippocampus and the anterior cingulate gyrus with three-dimension 1H-proton specrroscopy(3D 1H-MRS).Results:The values of NAA/Cr ratios in hippocampus and the anterior cingulate gyrus were significant lower in patients with post-traumatic stress disorder(1.71±0.32,left l.58±0.29, right 1.55±0.31) than that in controls(2.24±0.41,left 1.98±0.27,right 2.02±0.36)(P【0.05).but the values of Cho/Cr in hippocampus(left 1.64±0.23,right 1.66±0.34) were no significant with that of controls(left 1.48±0.29,right 1.54±0.38).Values of Cho/Cr in cingulate gyrus were significant higher in post-traumatic stress disorder patients(I.88±0.44) than that in controls(1.37.±0.32) (P【0.05).Conclusions:The results indicate some special neurochemical and histological structure changes in post-traumatic stress disorder patients,which might occurre earlier in anterior cingulate gyrusthe than in hippocampus.

Damage to Hippocampus of Rats after Being Exposed to Infrasound

Objective The objective was to observe damage of hippocampus in rats after exposure to infrasound, and to assess HSP70 expression in hippocampus. Methods SD rats in the experimental group were exposed to 140 d B（8 Hz） infrasound for 2 h per day for 3 days. The morphology of the hippocampus was examined by transmission electronic microscopic（TEM）. Cell apoptosis was observed by TUNEL staining at 0 h, 24 h, 48 h, and 2 w after exposure. HSP70 expression was detected by immunohistochemistry（IHC） and Western blotting（WB）. Results TEM showed that hippocampus was significantly damaged by exposure, and exhibited recovery 1 week after exposure. The TUNEL data showed that neuronal apoptosis after exposure was significantly higher than in the control rats at 24 h and 48 h, and the apoptotic cells decreased one week after exposure. IHC and WB showed HSP70 expression was significantly higher in the exposed rats, peaked at 24 h. Conclusion Exposure to 140 d B（8 Hz） infrasound for 2 h per day for 3 days appeared to induce damage to the hippocampus of rats, based on changes in ultrastructure and increased cell apoptosis. However, recovery from the damage occurred overtime. HSP70 expression also increased after the exposure and decreased by 48 h.

线纹海马(Hippocampus erectus)不同养殖密度下水体理化因子和细菌数量的动态变化

研究线纹海马(Hippocampus erectus)在室内水泥池不同养殖密度下,水体环境因子和细菌数量的动态变化情况。结果表明,在一个倒池换水周期中,养殖组1和养殖组2的磷酸磷(PO43--P)、硝酸氮(NO3--N)、亚硝酸氮(NO2--N)和氨氮(NH4+-N)等离子物质的浓度和细菌、弧菌和异养菌数量均随着养殖时间的推移不断上升,通常在换水后9d或12d达到最高,再次换水后降到极低值。单因素方差分析结果表明,在不同养殖密度下,PO43--P、NO3--N、NO2--N和NH4+-N等离子浓度随着养殖密度的升高而升高;而低密度养殖池中细菌数比高密度养殖池的细菌数显著更高。养殖水体中的PO43--P浓度与异养细菌数呈负相关关系,NO2--N浓度与细菌数量和弧菌数呈正相关关系,NO3--N浓度与细菌数、异养菌数和弧菌数呈负相关关系,NH4+-N浓度与细菌数、异养菌数和弧菌数均呈正相关关系。研究结果可为科学开展海马室内规模化养殖提供理论参考。

Tibolone modulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice

Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles （NFTs）; these hormones can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone （TIB） have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB （0.01 mg/kg and 1mg/kg, intragastrically for 12 weeks） on the content of total and hyperphosphorylated Tau （PHF-1） proteins and the regulation of GSK3β/Akt/PI3K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3β or PI3K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB： it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3β/Akt/PI3K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes.

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.

Downregulation of caveolin-1 contributes to the synaptic plasticity deficit in the hippocampus of aged rats

Caveolin-1 is involved in the regulation of synaptic plasticity, but the relationship between its ex-pression and cognitive function during aging remains controversial. To explore the relationship be-tween synaptic plasticity in the aging process and changes in learning and memory, we examined caveolin-1 expression in the hippocampus, cortex and cerebellum of rats at different ages. We also examined the relationship between the expression of caveolin-1 and synaptophysin, a marker of synaptic plasticity. Hippocampal caveolin-1 and synaptophysin expression in aged （22-24 month old） rats was significantly lower than that in young （1 month old） and adult （4 months old） rats. Ex- pression levels of both proteins were significantly greater in the cortex of aged rats than in that of young or adult rats, and levels were similar between the three age groups in the cerebellum. Linear regression analysis revealed that hippocampal expression of synaptophysin was associated with memory and learning abilities. Moreover, synaptophysin expression correlated positively with caveolin-1 expression in the hippocampus, cortex and cerebellum. These results confirm that caveolin-1 has a regulatory effect on synaptic plasticity, and suggest that the downregulation of hippocampal caveolin-1 expression causes a decrease in synaptic plasticity during physiological aging.