Alzheimer's disease is pathologically defined by accumulation of extracellular amyloid-β(Aβ). Approximately 25 mutations in β-amyloid precursor protein(APP) are pathogenic and cause autosomal dominant Alzheimer...Alzheimer's disease is pathologically defined by accumulation of extracellular amyloid-β(Aβ). Approximately 25 mutations in β-amyloid precursor protein(APP) are pathogenic and cause autosomal dominant Alzheimer's disease. To date, the mechanism underlying the effect of APP mutation on Aβ generation is unclear. Therefore, investigating the mechanism of APP mutation on Alzheimer's disease may help understanding of disease pathogenesis. Thus, APP mutations(A673T, A673 V, E682 K, E693 G, and E693Q) were transiently co-transfected into human embryonic kidney cells. Western blot assay was used to detect expression levels of APP, beta-secretase 1, and presenilin 1 in cells. Enzyme-linked immunosorbent assay was performed to determine Aβ_(1–40) and Aβ_(1–42) levels. Liquid chromatography-tandem mass chromatography was used to examine VVIAT, FLF, ITL, VIV, IAT, VIT, TVI, and VVIA peptide levels. Immunofluorescence staining was performed to measure APP and early endosome antigen 1 immunoreactivity. Our results show that the protective A673 T mutation decreases Aβ_(42)/Aβ_(40) rate by downregulating IAT and upregulating VVIA levels. Pathogenic A673 V, E682 K, and E693 Q mutations promote Aβ_(42)/Aβ_(40) rate by increasing levels of CTF99, Aβ_(42), Aβ_(40), and IAT, and decreasing VVIA levels. Pathogenic E693 G mutation shows no significant change in Aβ_(42)/Aβ_(40) ratio because of inhibition of γ-secretase activity. APP mutations can change location from the cell surface to early endosomes. Our findings confirm that certain APP mutations accelerate Aβ generation by affecting the long Aβ cleavage pathway and increasing Aβ_(42/40) rate, thereby resulting in Alzheimer's disease.展开更多
Background： Amyloid β （Aβ） has been established as a key factor for the pathological changes in the brains of patients with Alzheimer＇s disease （AD）, and cellular senescence is closely associated with aging an...Background： Amyloid β （Aβ） has been established as a key factor for the pathological changes in the brains of patients with Alzheimer＇s disease （AD）, and cellular senescence is closely associated with aging and cognitive impairment. However, it remains blurred whether, in theAD brains, Aβ accelerates the neuronal senescence and whether this senescence, in turn, impairs the cognitive function. This study aimed to explore the expression of senescence-associated genes in the hippocampal tissue from young to aged 5XFAD mice and their age-matched wild type （WT） mice to determine whether senescent neurons are present in the transgenic AD mouse model. Methods： The 5XFAD mice and age-matched wild type mice, both raised from 1 to 18 months, were enrolled in the study. The senescence-associated genes in the hippocampus were analyzed and differentially expressed genes （DEGs） were screened by quantitative real-time polymerase chain reaction. Cognitive perfom3ance of the mice was evaluated by Y-maze and Morris water maze tests. Oligomeric Aβ（oAβ） （1-42） was applied to culture primary neurons to simulate the in vivo manifestation. Aging-related proteins were detected by Western blotting analysis and immunofluorescence. Results： In 5XFAD mice, of all the DEGs, the senescence-associated marker p16 was most significantly increased, even at the early age. It was mainly localized in neurons, with a marginal expression in astrocytes （labeled as glutamine synthetase）, nil expression in activated microglia （labeled as lba1）, and negatively correlated with the spatial cognitive impairments of 5XFAD mice. oAβ （1-42） induced the production of senescence-related protein p1 6, but not p53 in vitro, which was in line with the in vivo manifestation. Conclusions： oAβ-accelerated neuronal senescence may be associated with the cognitive impairment in 5XFAD mice. Senescence-associated marker p16 can serve as an indicator to estimate the cognitive prognosis for A D population.展开更多
CD40 and its cognate ligand （CD40L） are a pair of regulators of pro-inflammatory and immune responses. In the central nervous system （CNS）, CD40 is expressed on a variety of cells, including vascular endothelial c...CD40 and its cognate ligand （CD40L） are a pair of regulators of pro-inflammatory and immune responses. In the central nervous system （CNS）, CD40 is expressed on a variety of cells, including vascular endothelial cells, smooth muscle cells, astrocytes and microglia （the brain macrophages, being the most sensitive cell type to respond to CD40 ligand）. Interaction between CD40 on microglia and CD40L presented by infiltrating T lymphocytes and other resident CNS cells triggers a series of intracellular signaling events that promote the production of a wide array of cytokines, chemokines and neurotoxins. Thus, both molecules serve as amplifiers of pro-inflammatory and immune responses in the CNS and constitute important molecular targets for therapeutic intervention of diseases.Cellular ＆ Molecular Immunology. 2006;3（3）：163-169.展开更多
Amyloid-beta(Aβ)plays a pivotal role in the pathogenesis of Alzheimer's disease(AD)and has been regarded as the main therapeutic target for AD.However,most of the Aβ-targeted clinical trials have not succeeded.T...Amyloid-beta(Aβ)plays a pivotal role in the pathogenesis of Alzheimer's disease(AD)and has been regarded as the main therapeutic target for AD.However,most of the Aβ-targeted clinical trials have not succeeded.Therefore,the Aβ-targeted therapeutic strategy on treating this complex disease needs to be re-evaluated.In this review,we analyzed the challenges and critical points of the current anti-Aβtherapeutic strategies.In addition to Aβ,multiple pathological events such as tau hyperphosphorylation,oxidative stress,and neuroinflammation,which are involved in AD pathogenesis and synergistically drive disease progression,could be important targets for AD treatment.Tertiary prevention strategies are needed for the successful management of AD due to its complex and dynamic pathogenesis.Systemic perspective addressing the disease pathogenesis within and outside the brain,as well as the multidomain intervention targeting risk factors and comorbidities,are important approaches for the therapeutic solutions of AD.展开更多
Neurotropic herpesviruses have been associated with the onset and progression of Alzheimer’s disease,a common form of dementia that afflicts a large percentage of elderly individuals.Interestingly,among the neurotrop...Neurotropic herpesviruses have been associated with the onset and progression of Alzheimer’s disease,a common form of dementia that afflicts a large percentage of elderly individuals.Interestingly,among the neurotropic herpesviruses,herpes simplex virus-1,human herpesvirus-6A,and human herpesvirus-6B have been reported to infect several cell types present in the central nervous system and to dysregulate autophagy,a process required for homeostasis of cells,especially neurons.Indeed autophagosome accumulation,indicating an unbalance between autophagosome formation and autophagosome degradation,has been observed in neurons of Alzheimer’s disease patients and may play a role in the intracellular and extracellular accumulation of amyloidβand in the altered protein tau metabolism.Moreover,herpesvirus infection of central nervous system cells such as glia and microglia can increase the production of oxidant species through the alteration of mitochondrial dynamics and promote inflammation,another hallmark of Alzheimer’s disease.This evidence suggests that it is worth further investigating the role of neurotropic herpesviruses,particularly human herpesvirus-6A/B,in the etiopathogenesis of Alzheimer’s disease.展开更多
BACKGROUND Atrophic gastritis is characterized by loss of appropriate glands and reduction in gastric secretory function due to chronic inflammatory processes in gastric mucosa. Moreover, atrophic gastritis is conside...BACKGROUND Atrophic gastritis is characterized by loss of appropriate glands and reduction in gastric secretory function due to chronic inflammatory processes in gastric mucosa. Moreover, atrophic gastritis is considered as a precancerous condition of gastric cancer. However, little is known about the molecular mechanism underlying gastric mucosal atrophy and its contribution to gastric carcinogenesis.Thus, we hypothesized that transcription factor NKX6.3 might be involved in maintaining gastric epithelial homeostasis by regulating amyloid β(Aβ)production.AIM To determine whether NKX6.3 might protect against gastric mucosal atrophy by regulating Aβ production.METHODS We identified NKX6.3 depletion induced cell death by cell count and Western blot assay. Production and mechanism of Aβ oligomer were analyzed by enzymelinked immunosorbent assay, Western blot, immunoprecipitation, real-timequantitative polymerase chain reaction and immunofluorescence analysis. We further validated the correlation between expression of NKX6.3, Helicobacter pylori CagA, Aβ oligomer, apolipoprotein E(ApoE), and β-secretase 1(Bace1) in 55 gastric mucosae.RESULTS NKX6.3 depletion increased both adherent and floating cell populations in HFE-145 cells. Expression levels of cleaved caspase-3,-9, and poly ADP ribose polymerase were elevated in floating HFE-145^(shNKX6.3) cells. NKX6.3 depletion produced Aβ peptide oligomers, and increased expression of ApoE, amyloid precursor protein, Aβ, Bace1, low-density lipoprotein receptor, nicastrin, high mobility group box1, and receptor for advanced glycosylation end product proteins. In immunoprecipitation assay, γ-secretase complex was stably formed only in HFE-145^(shNKX6.3) cells. In gastric mucosae with atrophy, expression of Aβpeptide oligomer, ApoE, and Bace1 was detected and inversely correlated with NKX6.3 expression. Treatment with recombinant Aβ 1-42 produced Aβoligomeric forms and decreased cell viability in HFE-145^(shNKX6.3) cells. Additionally,NKX6.3 depletion increased expr展开更多
Background： Amyloid β （Aβ） deposits and the endoplasmic reticulum stress （ERS） are both well established in the development and progression of Alzheimer＇s disease （AD）. However, the mechanism and role of Aβ...Background： Amyloid β （Aβ） deposits and the endoplasmic reticulum stress （ERS） are both well established in the development and progression of Alzheimer＇s disease （AD）. However, the mechanism and role of Aβ-induced ERS in AD-associated pathological progression remain to be elucidated. Methods： The five familial AD （5×FAD） mice and wild-type （WT） mice aged 2, 7, and 12 months were used in the present study. Monis water maze test was used to evaluate their cognitive performance, lmmunofluorescence and Western blot analyses were used to examine the dynamic changes of pro-apoptotic （CCAAT/enhancer-binding protein homologous protein [CHOP] and cleaved caspase-12） and anti-apoptotic factors （chaperone glucose-regulated protein [GRP] 78 and endoplasmic reticulum-associated protein degradation-associated ubiquitin ligase synovial apoptosis inhibitor 1 [SYVN 1]） in the ERS-associated unfolded protein response （UPR） pathway. Results： Compared with age-matched WT mice, 5 xFAD mice showed higher cleaved caspase-3, lower neuron-positive staining at the age of 12 months, but earlier cognitive deficit at the age of 7 months （all P 〈 0.05）. Interestingly, for 2-month-old 5×FAD mice, the related proteins involved in the ERS-associated UPR pathway, including CHOP, cleaved caspase-12, GRP 78, and SYVN 1, were significantly increased when compared with those in age-matched WT mice （all P 〈 0.05）. Moreover, ERS occurred mainly in neurons, not in astrocytes. Conclusions： These findings suggest that compared with those of age-matched WT mice, ERS-associated pro-apoptotic and anti-apoptotic proteins are upregulated in 2-month-old 5×FAD mice, consistent with intracellular Aβ aggregation in neurons.展开更多
Impaired hippocampal neurogenesis is one of the early pathological features of Alzheimer＇s disease. Enhancing adult hippocampal neuro- genesis has been pursued as a potential therapeutic strategy for Alzheimer＇s dis...Impaired hippocampal neurogenesis is one of the early pathological features of Alzheimer＇s disease. Enhancing adult hippocampal neuro- genesis has been pursued as a potential therapeutic strategy for Alzheimer＇s disease. Recent studies have demonstrated that environmental novelty activates β2-adrenergic signaling and prevents the memory impairment induced by amyloid-β oligomers. Here, we hypothesized that β2-adrenoceptor activation would enhance neurogenesis and ameliorate memory deficits in Alzheimer＇s disease. To test this hypothe- sis, we investigated the effects and mechanisms of action of β2-adrenoceptor activation on neurogenesis and memory in amyloid precursor protein/presenilin 1 （APP/PS1） mice using the agonist clenbuterol （intraperitoneal injection, 2 mg/kg）. We found that β2-adrenoceptor ac- tivation enhanced hippocampal neurogenesis, ameliorated memory deficits, and increased dendritic branching and the density of dendritic spines, lhese effects were associated with the upregulation of postsynaptic density 95, synapsin 1 and synaptophysin in APP/PS1 mice. Furthermore, β2-adrenoceptor activation decreased cerebral amyloid plaques by decreasing APP phosphorylation at Thr668. These findings suggest that β2-adrenoceptor activation enhances neurogenesis and ameliorates memory deficits in APP/PS 1 mice.展开更多
基金funded by the National Natural Science Foundation of China,No.81671268(to HQ)partially supported by a grant from the Ministry of Science and Technology of China,No.2013YQ03059514(to HQ)a grant from Key Laboratory for Neurodegenerative Disease of Ministry of Education of China,No.2015SJBX05(to HQ),2015SJZS01(to HQ)
文摘Alzheimer's disease is pathologically defined by accumulation of extracellular amyloid-β(Aβ). Approximately 25 mutations in β-amyloid precursor protein(APP) are pathogenic and cause autosomal dominant Alzheimer's disease. To date, the mechanism underlying the effect of APP mutation on Aβ generation is unclear. Therefore, investigating the mechanism of APP mutation on Alzheimer's disease may help understanding of disease pathogenesis. Thus, APP mutations(A673T, A673 V, E682 K, E693 G, and E693Q) were transiently co-transfected into human embryonic kidney cells. Western blot assay was used to detect expression levels of APP, beta-secretase 1, and presenilin 1 in cells. Enzyme-linked immunosorbent assay was performed to determine Aβ_(1–40) and Aβ_(1–42) levels. Liquid chromatography-tandem mass chromatography was used to examine VVIAT, FLF, ITL, VIV, IAT, VIT, TVI, and VVIA peptide levels. Immunofluorescence staining was performed to measure APP and early endosome antigen 1 immunoreactivity. Our results show that the protective A673 T mutation decreases Aβ_(42)/Aβ_(40) rate by downregulating IAT and upregulating VVIA levels. Pathogenic A673 V, E682 K, and E693 Q mutations promote Aβ_(42)/Aβ_(40) rate by increasing levels of CTF99, Aβ_(42), Aβ_(40), and IAT, and decreasing VVIA levels. Pathogenic E693 G mutation shows no significant change in Aβ_(42)/Aβ_(40) ratio because of inhibition of γ-secretase activity. APP mutations can change location from the cell surface to early endosomes. Our findings confirm that certain APP mutations accelerate Aβ generation by affecting the long Aβ cleavage pathway and increasing Aβ_(42/40) rate, thereby resulting in Alzheimer's disease.
基金We would like to thank teacher Hong-Zhi Huang from College of Foreign Languages of Fujian Medical University for the kindly help of text modifications and retouching of this paper. This study was supported by grants from National Natural Science Fotmdation of China （No. 81200991 and No. 81571257）, Fujian Provincial Natural Science Foundation （No. 2015J01398）, Fujian Provincial New Century Excellent Talents Support Program, China （JA13131）, and Young and Middle-aged Talent Training Key Project in Health System of Fujian Province （2014-ZQN-ZD- 11）.
文摘Background： Amyloid β （Aβ） has been established as a key factor for the pathological changes in the brains of patients with Alzheimer＇s disease （AD）, and cellular senescence is closely associated with aging and cognitive impairment. However, it remains blurred whether, in theAD brains, Aβ accelerates the neuronal senescence and whether this senescence, in turn, impairs the cognitive function. This study aimed to explore the expression of senescence-associated genes in the hippocampal tissue from young to aged 5XFAD mice and their age-matched wild type （WT） mice to determine whether senescent neurons are present in the transgenic AD mouse model. Methods： The 5XFAD mice and age-matched wild type mice, both raised from 1 to 18 months, were enrolled in the study. The senescence-associated genes in the hippocampus were analyzed and differentially expressed genes （DEGs） were screened by quantitative real-time polymerase chain reaction. Cognitive perfom3ance of the mice was evaluated by Y-maze and Morris water maze tests. Oligomeric Aβ（oAβ） （1-42） was applied to culture primary neurons to simulate the in vivo manifestation. Aging-related proteins were detected by Western blotting analysis and immunofluorescence. Results： In 5XFAD mice, of all the DEGs, the senescence-associated marker p16 was most significantly increased, even at the early age. It was mainly localized in neurons, with a marginal expression in astrocytes （labeled as glutamine synthetase）, nil expression in activated microglia （labeled as lba1）, and negatively correlated with the spatial cognitive impairments of 5XFAD mice. oAβ （1-42） induced the production of senescence-related protein p1 6, but not p53 in vitro, which was in line with the in vivo manifestation. Conclusions： oAβ-accelerated neuronal senescence may be associated with the cognitive impairment in 5XFAD mice. Senescence-associated marker p16 can serve as an indicator to estimate the cognitive prognosis for A D population.
文摘CD40 and its cognate ligand （CD40L） are a pair of regulators of pro-inflammatory and immune responses. In the central nervous system （CNS）, CD40 is expressed on a variety of cells, including vascular endothelial cells, smooth muscle cells, astrocytes and microglia （the brain macrophages, being the most sensitive cell type to respond to CD40 ligand）. Interaction between CD40 on microglia and CD40L presented by infiltrating T lymphocytes and other resident CNS cells triggers a series of intracellular signaling events that promote the production of a wide array of cytokines, chemokines and neurotoxins. Thus, both molecules serve as amplifiers of pro-inflammatory and immune responses in the CNS and constitute important molecular targets for therapeutic intervention of diseases.Cellular ＆ Molecular Immunology. 2006;3（3）：163-169.
基金supported by the National Natural Science Foundation of China(91749206,81930028,81625007,81870860,31921003)。
文摘Amyloid-beta(Aβ)plays a pivotal role in the pathogenesis of Alzheimer's disease(AD)and has been regarded as the main therapeutic target for AD.However,most of the Aβ-targeted clinical trials have not succeeded.Therefore,the Aβ-targeted therapeutic strategy on treating this complex disease needs to be re-evaluated.In this review,we analyzed the challenges and critical points of the current anti-Aβtherapeutic strategies.In addition to Aβ,multiple pathological events such as tau hyperphosphorylation,oxidative stress,and neuroinflammation,which are involved in AD pathogenesis and synergistically drive disease progression,could be important targets for AD treatment.Tertiary prevention strategies are needed for the successful management of AD due to its complex and dynamic pathogenesis.Systemic perspective addressing the disease pathogenesis within and outside the brain,as well as the multidomain intervention targeting risk factors and comorbidities,are important approaches for the therapeutic solutions of AD.
基金supported by Human Herpesvirus-6 Foundation and Istituto Pasteur Italia-Fondazione Cenci Bolognetti(to MC)
文摘Neurotropic herpesviruses have been associated with the onset and progression of Alzheimer’s disease,a common form of dementia that afflicts a large percentage of elderly individuals.Interestingly,among the neurotropic herpesviruses,herpes simplex virus-1,human herpesvirus-6A,and human herpesvirus-6B have been reported to infect several cell types present in the central nervous system and to dysregulate autophagy,a process required for homeostasis of cells,especially neurons.Indeed autophagosome accumulation,indicating an unbalance between autophagosome formation and autophagosome degradation,has been observed in neurons of Alzheimer’s disease patients and may play a role in the intracellular and extracellular accumulation of amyloidβand in the altered protein tau metabolism.Moreover,herpesvirus infection of central nervous system cells such as glia and microglia can increase the production of oxidant species through the alteration of mitochondrial dynamics and promote inflammation,another hallmark of Alzheimer’s disease.This evidence suggests that it is worth further investigating the role of neurotropic herpesviruses,particularly human herpesvirus-6A/B,in the etiopathogenesis of Alzheimer’s disease.
基金Supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Science and Technology,No.2018R1A2A2A14019713 to Park WS
文摘BACKGROUND Atrophic gastritis is characterized by loss of appropriate glands and reduction in gastric secretory function due to chronic inflammatory processes in gastric mucosa. Moreover, atrophic gastritis is considered as a precancerous condition of gastric cancer. However, little is known about the molecular mechanism underlying gastric mucosal atrophy and its contribution to gastric carcinogenesis.Thus, we hypothesized that transcription factor NKX6.3 might be involved in maintaining gastric epithelial homeostasis by regulating amyloid β(Aβ)production.AIM To determine whether NKX6.3 might protect against gastric mucosal atrophy by regulating Aβ production.METHODS We identified NKX6.3 depletion induced cell death by cell count and Western blot assay. Production and mechanism of Aβ oligomer were analyzed by enzymelinked immunosorbent assay, Western blot, immunoprecipitation, real-timequantitative polymerase chain reaction and immunofluorescence analysis. We further validated the correlation between expression of NKX6.3, Helicobacter pylori CagA, Aβ oligomer, apolipoprotein E(ApoE), and β-secretase 1(Bace1) in 55 gastric mucosae.RESULTS NKX6.3 depletion increased both adherent and floating cell populations in HFE-145 cells. Expression levels of cleaved caspase-3,-9, and poly ADP ribose polymerase were elevated in floating HFE-145^(shNKX6.3) cells. NKX6.3 depletion produced Aβ peptide oligomers, and increased expression of ApoE, amyloid precursor protein, Aβ, Bace1, low-density lipoprotein receptor, nicastrin, high mobility group box1, and receptor for advanced glycosylation end product proteins. In immunoprecipitation assay, γ-secretase complex was stably formed only in HFE-145^(shNKX6.3) cells. In gastric mucosae with atrophy, expression of Aβpeptide oligomer, ApoE, and Bace1 was detected and inversely correlated with NKX6.3 expression. Treatment with recombinant Aβ 1-42 produced Aβoligomeric forms and decreased cell viability in HFE-145^(shNKX6.3) cells. Additionally,NKX6.3 depletion increased expr
基金This work was supported by grants from the National Natural Science Foundation of China （No. 91232709, No. 811171216, and No. 81161120496 for Prof. Xiao-Chun Chen, and No. 81200991 for Prof. Xiao-Dong Pan） and the National and Fujian Province＇s Key Clinical Specialty Discipline Construction Programs.
文摘Background： Amyloid β （Aβ） deposits and the endoplasmic reticulum stress （ERS） are both well established in the development and progression of Alzheimer＇s disease （AD）. However, the mechanism and role of Aβ-induced ERS in AD-associated pathological progression remain to be elucidated. Methods： The five familial AD （5×FAD） mice and wild-type （WT） mice aged 2, 7, and 12 months were used in the present study. Monis water maze test was used to evaluate their cognitive performance, lmmunofluorescence and Western blot analyses were used to examine the dynamic changes of pro-apoptotic （CCAAT/enhancer-binding protein homologous protein [CHOP] and cleaved caspase-12） and anti-apoptotic factors （chaperone glucose-regulated protein [GRP] 78 and endoplasmic reticulum-associated protein degradation-associated ubiquitin ligase synovial apoptosis inhibitor 1 [SYVN 1]） in the ERS-associated unfolded protein response （UPR） pathway. Results： Compared with age-matched WT mice, 5 xFAD mice showed higher cleaved caspase-3, lower neuron-positive staining at the age of 12 months, but earlier cognitive deficit at the age of 7 months （all P 〈 0.05）. Interestingly, for 2-month-old 5×FAD mice, the related proteins involved in the ERS-associated UPR pathway, including CHOP, cleaved caspase-12, GRP 78, and SYVN 1, were significantly increased when compared with those in age-matched WT mice （all P 〈 0.05）. Moreover, ERS occurred mainly in neurons, not in astrocytes. Conclusions： These findings suggest that compared with those of age-matched WT mice, ERS-associated pro-apoptotic and anti-apoptotic proteins are upregulated in 2-month-old 5×FAD mice, consistent with intracellular Aβ aggregation in neurons.
基金supported by the National Natural Science Foundation of China,No.81601121,31500968the Natural Science Foundation of Jiangsu Province of China,No.BK20150163the Fundamental Research Fund for the Central Universities of China,No.JUSRP11567
文摘Impaired hippocampal neurogenesis is one of the early pathological features of Alzheimer＇s disease. Enhancing adult hippocampal neuro- genesis has been pursued as a potential therapeutic strategy for Alzheimer＇s disease. Recent studies have demonstrated that environmental novelty activates β2-adrenergic signaling and prevents the memory impairment induced by amyloid-β oligomers. Here, we hypothesized that β2-adrenoceptor activation would enhance neurogenesis and ameliorate memory deficits in Alzheimer＇s disease. To test this hypothe- sis, we investigated the effects and mechanisms of action of β2-adrenoceptor activation on neurogenesis and memory in amyloid precursor protein/presenilin 1 （APP/PS1） mice using the agonist clenbuterol （intraperitoneal injection, 2 mg/kg）. We found that β2-adrenoceptor ac- tivation enhanced hippocampal neurogenesis, ameliorated memory deficits, and increased dendritic branching and the density of dendritic spines, lhese effects were associated with the upregulation of postsynaptic density 95, synapsin 1 and synaptophysin in APP/PS1 mice. Furthermore, β2-adrenoceptor activation decreased cerebral amyloid plaques by decreasing APP phosphorylation at Thr668. These findings suggest that β2-adrenoceptor activation enhances neurogenesis and ameliorates memory deficits in APP/PS 1 mice.
