Pub Date : 2021-11-24DOI: 10.5772/intechopen.101299
Dandan Chu, Fei Liu
Tau, one of the major microtubule-associated proteins, modulates the dynamic properties of microtubules in the mammalian nervous system. Tau is abundantly expressed in the brain, particularly in the hippocampus. Insoluble and filamentous inclusions of tau in neurons or glia are discovered in neurodegenerative diseases termed ‘tauopathies’, including Alzheimer’s disease (AD), argyrophilic grain disease (AGD), corticobasal degeneration (CBD), frontotemporal dementia (FTD), Pick’s disease (PiD) and progressive supranuclear palsy (PSP). Accumulation of intracellular neurofibrillary tangles (NFTs), which are composed of hyperphosphorylated tau, is directly correlated with the degree of Alzheimer's dementia. This chapter reviews the role of tau protein in physiological conditions and the pathological changes of tau related to neurodegenerative diseases. The applications of tau as a therapeutic target are also discussed.
{"title":"Tau in Health and Neurodegenerative Diseases","authors":"Dandan Chu, Fei Liu","doi":"10.5772/intechopen.101299","DOIUrl":"https://doi.org/10.5772/intechopen.101299","url":null,"abstract":"Tau, one of the major microtubule-associated proteins, modulates the dynamic properties of microtubules in the mammalian nervous system. Tau is abundantly expressed in the brain, particularly in the hippocampus. Insoluble and filamentous inclusions of tau in neurons or glia are discovered in neurodegenerative diseases termed ‘tauopathies’, including Alzheimer’s disease (AD), argyrophilic grain disease (AGD), corticobasal degeneration (CBD), frontotemporal dementia (FTD), Pick’s disease (PiD) and progressive supranuclear palsy (PSP). Accumulation of intracellular neurofibrillary tangles (NFTs), which are composed of hyperphosphorylated tau, is directly correlated with the degree of Alzheimer's dementia. This chapter reviews the role of tau protein in physiological conditions and the pathological changes of tau related to neurodegenerative diseases. The applications of tau as a therapeutic target are also discussed.","PeriodicalId":169305,"journal":{"name":"Hippocampus - New Advances [Working Title]","volume":"99 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124925664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-11-24DOI: 10.5772/intechopen.100334
Kun Jiang, Yongqi Zhu, Lei Zhang
Alzheimer’s disease (AD) is a kind of neurodegenerative disease with insidious onset and progressive progression. The etiology of AD may be related to the loss of neurons, astrocytes, and microglial in the nervous system. Exogenous stem cell transplantation has brought hope to the treatment of AD. Stem cell transplantation can reduce amyloid β-protein (Aβ) deposition and Tau phosphorylation, and provide secretory factor support to improve learning and memory deficits. The purpose of this review is to provide an overview of the relationship between different stem cell species and the treatment of AD, and also summarize current experimental stem cell therapy strategies and their potential clinical applications in the future.
{"title":"New Prospects for Stem Cell Therapy in Alzheimer’s Disease","authors":"Kun Jiang, Yongqi Zhu, Lei Zhang","doi":"10.5772/intechopen.100334","DOIUrl":"https://doi.org/10.5772/intechopen.100334","url":null,"abstract":"Alzheimer’s disease (AD) is a kind of neurodegenerative disease with insidious onset and progressive progression. The etiology of AD may be related to the loss of neurons, astrocytes, and microglial in the nervous system. Exogenous stem cell transplantation has brought hope to the treatment of AD. Stem cell transplantation can reduce amyloid β-protein (Aβ) deposition and Tau phosphorylation, and provide secretory factor support to improve learning and memory deficits. The purpose of this review is to provide an overview of the relationship between different stem cell species and the treatment of AD, and also summarize current experimental stem cell therapy strategies and their potential clinical applications in the future.","PeriodicalId":169305,"journal":{"name":"Hippocampus - New Advances [Working Title]","volume":"100 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124121554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-11-03DOI: 10.5772/intechopen.100898
Fatima M.C. Bastos, Carlos M. Matias, Ines O. Lopes, João P. Vieira, Rosa M. Santos, Luís M. Rosário, Rosa M. Quinta-Ferreira, M. Emília Quinta-Ferreira
Glutamatergic vesicles in hippocampal mossy fiber presynaptic boutons release zinc, which plays a modulatory role in synaptic activity and LTP. In this work, a fluorescence microscopy technique and the fluorescent probe for cytosolic zinc, Newport Green (NG), were applied, in a combined study of autofluorescence and zinc changes at the hippocampal mossy fiber-CA3 synaptic system. In particular, the dynamics of flavoprotein (FAD) autofluorescence signals, was compared to that of postsynaptic zinc signals, elicited both by high K+ (20 mM) and by tetraethylammonium (TEA, 25 mM). The real zinc signals were obtained subtracting autofluorescence values, from corresponding total NG-fluorescence data. Both autofluorescence and zinc-related fluorescence were raised by high K+. In contrast, the same signals were reduced during TEA exposure. It is suggested that the initial outburst of TEA-evoked zinc release might activate ATP-sensitive K+ (KATP) channels, as part of a safeguard mechanism against excessive glutamatergic action. This would cause sustained inhibition of zinc signals and a more reduced mitochondrial state. In favor of the “KATP channel hypothesis”, the KATP channel blocker tolbutamide (250 μM) nearly suppressed the TEA-evoked fluorescence changes. It is concluded that recording autofluorescence from brain slices is essential for the accurate assessment of zinc signals and actions.
海马苔藓纤维突触前钮扣中的谷氨酸能小泡释放锌，锌在突触活性和LTP中起调节作用。本研究采用荧光显微技术和胞质锌荧光探针Newport Green (NG)，对海马苔藓纤维- ca3突触系统的自身荧光和锌的变化进行了联合研究。特别地，我们比较了黄蛋白(FAD)自身荧光信号与高K+ (20 mM)和四乙基铵(25 mM)诱导的突触后锌信号的动态。实际锌信号减去自身荧光值，从相应的总ng荧光数据。高K+提高了自身荧光和锌相关荧光。相比之下，同样的信号在TEA暴露期间减少了。这表明，茶引起的锌释放的初始爆发可能激活atp敏感的K+ (KATP)通道，作为防止过度谷氨酸作用的保护机制的一部分。这将导致锌信号的持续抑制和线粒体状态的进一步减少。支持“KATP通道假说”的是，KATP通道阻滞剂tolbuamide (250 μM)几乎抑制了tea引起的荧光变化。因此，记录脑切片的自身荧光对于准确评估锌的信号和作用是必要的。
{"title":"FAD-Linked Autofluorescence and Chemically-Evoked Zinc Changes at Hippocampal Mossy Fiber-CA3 Synapses","authors":"Fatima M.C. Bastos, Carlos M. Matias, Ines O. Lopes, João P. Vieira, Rosa M. Santos, Luís M. Rosário, Rosa M. Quinta-Ferreira, M. Emília Quinta-Ferreira","doi":"10.5772/intechopen.100898","DOIUrl":"https://doi.org/10.5772/intechopen.100898","url":null,"abstract":"Glutamatergic vesicles in hippocampal mossy fiber presynaptic boutons release zinc, which plays a modulatory role in synaptic activity and LTP. In this work, a fluorescence microscopy technique and the fluorescent probe for cytosolic zinc, Newport Green (NG), were applied, in a combined study of autofluorescence and zinc changes at the hippocampal mossy fiber-CA3 synaptic system. In particular, the dynamics of flavoprotein (FAD) autofluorescence signals, was compared to that of postsynaptic zinc signals, elicited both by high K+ (20 mM) and by tetraethylammonium (TEA, 25 mM). The real zinc signals were obtained subtracting autofluorescence values, from corresponding total NG-fluorescence data. Both autofluorescence and zinc-related fluorescence were raised by high K+. In contrast, the same signals were reduced during TEA exposure. It is suggested that the initial outburst of TEA-evoked zinc release might activate ATP-sensitive K+ (KATP) channels, as part of a safeguard mechanism against excessive glutamatergic action. This would cause sustained inhibition of zinc signals and a more reduced mitochondrial state. In favor of the “KATP channel hypothesis”, the KATP channel blocker tolbutamide (250 μM) nearly suppressed the TEA-evoked fluorescence changes. It is concluded that recording autofluorescence from brain slices is essential for the accurate assessment of zinc signals and actions.","PeriodicalId":169305,"journal":{"name":"Hippocampus - New Advances [Working Title]","volume":"44 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124728412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-25DOI: 10.5772/intechopen.100620
C. Jara, Débora Buendía, Álvaro O. Ardiles, P. Muñoz, Cheril Tapia-Rojas
The hippocampus is an integral portion of the limbic system and executes a critical role in spatial and recognition learning, memory encoding, and memory consolidation. Hippocampal aging showed neurobiological alterations, including increased oxidative stress, altered intracellular signaling pathways, synaptic impairment, and organelle deterioration such as mitochondrial dysfunction. These alterations lead to hippocampal cognitive decline during aging. Therefore, the search for new non-invasive therapies focused on preserving or attenuating age-related hippocampal memory impairment could have of great impact on aging, considering the increasing life expectancy in the world. Red light Transcranial LED therapy (RL-TCLT) is a promising but little explored strategy, which involves red light LED irradiation without surgical procedures, safe and at a low cost. Nevertheless, the precise mechanism involved and its real impact on age-related cognitive impairment is unclear, due to differences in protocol, wavelength applied, and time. Therefore, in this chapter, we will discuss the evidence about RL-TCLT and its effects on the hippocampal structure and function, and how this therapy could be used as a promising treatment for memory loss during aging and in age-related diseases such as Alzheimer’s Disease (AD). Finally, we will mention our advances in Red 630-light-Transcranial LED therapy on the hippocampus in aging and AD.
{"title":"Transcranial Red LED Therapy: A Promising Non-Invasive Treatment to Prevent Age-Related Hippocampal Memory Impairment","authors":"C. Jara, Débora Buendía, Álvaro O. Ardiles, P. Muñoz, Cheril Tapia-Rojas","doi":"10.5772/intechopen.100620","DOIUrl":"https://doi.org/10.5772/intechopen.100620","url":null,"abstract":"The hippocampus is an integral portion of the limbic system and executes a critical role in spatial and recognition learning, memory encoding, and memory consolidation. Hippocampal aging showed neurobiological alterations, including increased oxidative stress, altered intracellular signaling pathways, synaptic impairment, and organelle deterioration such as mitochondrial dysfunction. These alterations lead to hippocampal cognitive decline during aging. Therefore, the search for new non-invasive therapies focused on preserving or attenuating age-related hippocampal memory impairment could have of great impact on aging, considering the increasing life expectancy in the world. Red light Transcranial LED therapy (RL-TCLT) is a promising but little explored strategy, which involves red light LED irradiation without surgical procedures, safe and at a low cost. Nevertheless, the precise mechanism involved and its real impact on age-related cognitive impairment is unclear, due to differences in protocol, wavelength applied, and time. Therefore, in this chapter, we will discuss the evidence about RL-TCLT and its effects on the hippocampal structure and function, and how this therapy could be used as a promising treatment for memory loss during aging and in age-related diseases such as Alzheimer’s Disease (AD). Finally, we will mention our advances in Red 630-light-Transcranial LED therapy on the hippocampus in aging and AD.","PeriodicalId":169305,"journal":{"name":"Hippocampus - New Advances [Working Title]","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114121395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-03DOI: 10.5772/intechopen.100310
Yi-Xiao Luo, M. Toso, Bailu Si, Federico Stella, A. Treves
Spatial cognition in naturalistic environments, for freely moving animals, may pose quite different constraints from that studied in artificial laboratory settings. Hippocampal place cells indeed look quite different, but almost nothing is known about entorhinal cortex grid cells, in the wild. Simulating our self-organizing adaptation model of grid cell pattern formation, we consider a virtual rat randomly exploring a virtual burrow, with feedforward connectivity from place to grid units and recurrent connectivity between grid units. The virtual burrow was based on those observed by John B. Calhoun, including several chambers and tunnels. Our results indicate that lateral connectivity between grid units may enhance their “gridness” within a limited strength range, but the overall effect of the irregular geometry is to disable long-range and obstruct short-range order. What appears as a smooth continuous attractor in a flat box, kept rigid by recurrent connections, turns into an incoherent motley of unit clusters, flexible or outright unstable.
{"title":"Grid Cells Lose Coherence in Realistic Environments","authors":"Yi-Xiao Luo, M. Toso, Bailu Si, Federico Stella, A. Treves","doi":"10.5772/intechopen.100310","DOIUrl":"https://doi.org/10.5772/intechopen.100310","url":null,"abstract":"Spatial cognition in naturalistic environments, for freely moving animals, may pose quite different constraints from that studied in artificial laboratory settings. Hippocampal place cells indeed look quite different, but almost nothing is known about entorhinal cortex grid cells, in the wild. Simulating our self-organizing adaptation model of grid cell pattern formation, we consider a virtual rat randomly exploring a virtual burrow, with feedforward connectivity from place to grid units and recurrent connectivity between grid units. The virtual burrow was based on those observed by John B. Calhoun, including several chambers and tunnels. Our results indicate that lateral connectivity between grid units may enhance their “gridness” within a limited strength range, but the overall effect of the irregular geometry is to disable long-range and obstruct short-range order. What appears as a smooth continuous attractor in a flat box, kept rigid by recurrent connections, turns into an incoherent motley of unit clusters, flexible or outright unstable.","PeriodicalId":169305,"journal":{"name":"Hippocampus - New Advances [Working Title]","volume":"77 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124520382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-20DOI: 10.5772/intechopen.100203
Siwei Xu, Yaya Ji, T. Sha, Haoming Li
Alzheimer’s disease (AD) is one of the most common causes of dementia all around the world. It is characterized by the deposition of amyloid-β protein (Aβ) and the formation of neurofibrillary tangles (NFTs), which contribute to neuronal loss and cognitive decline. Microglia, as innate immune cells in brain, plays dual roles in the pathological process of AD. Expression in different subtypes of microglia is diverse in AD genes. Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane glycoprotein mainly expressed on microglia in the central nervous system (CNS). Soluble TREM2 (sTREM2), a proteolytic product of TREM2, which is abundant in the cerebrospinal fluid, shows a dynamic change in different stages and ameliorates the pathological process of AD. The interplay between the different subtypes of apolipoprotein and TREM2 is closely related to the mechanism of AD and serves as important regulatory sites. Moreover, several therapeutic strategies targeting TREM2 have shown positive outcomes during clinical trials and some novel therapies at different points are in progress. In this review, we mainly talk about the interrelationships among microglia, TREM2, and AD, and hope to give an overview of the strategies of AD.
{"title":"Microglia, TREM2, and Therapeutic Methods of Alzheimer’s Disease","authors":"Siwei Xu, Yaya Ji, T. Sha, Haoming Li","doi":"10.5772/intechopen.100203","DOIUrl":"https://doi.org/10.5772/intechopen.100203","url":null,"abstract":"Alzheimer’s disease (AD) is one of the most common causes of dementia all around the world. It is characterized by the deposition of amyloid-β protein (Aβ) and the formation of neurofibrillary tangles (NFTs), which contribute to neuronal loss and cognitive decline. Microglia, as innate immune cells in brain, plays dual roles in the pathological process of AD. Expression in different subtypes of microglia is diverse in AD genes. Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane glycoprotein mainly expressed on microglia in the central nervous system (CNS). Soluble TREM2 (sTREM2), a proteolytic product of TREM2, which is abundant in the cerebrospinal fluid, shows a dynamic change in different stages and ameliorates the pathological process of AD. The interplay between the different subtypes of apolipoprotein and TREM2 is closely related to the mechanism of AD and serves as important regulatory sites. Moreover, several therapeutic strategies targeting TREM2 have shown positive outcomes during clinical trials and some novel therapies at different points are in progress. In this review, we mainly talk about the interrelationships among microglia, TREM2, and AD, and hope to give an overview of the strategies of AD.","PeriodicalId":169305,"journal":{"name":"Hippocampus - New Advances [Working Title]","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132613433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-01DOI: 10.5772/intechopen.99895
S. Vafaei-Nezhad, Masood Vafaei-Nezhad, Mehri Shadi, Samira Ezi
Maternal Diabetes is one of the most common metabolic disorders resulting an increased risk of abnormalities in the developing fetus and offspring. It is estimated that the prevalence of diabetes during pregnancy among women in developing countries is approximately 4.5 percent and this range varies between 1 to 14 percent in different societies. According to earlier studies, diabetes during pregnancy is associated with an increased risk of maternal and child mortality and morbidity as well as major congenital anomalies including central nervous system (CNS) in their offspring. Multiple lines of evidence have suggested that infants of diabetic women are at risk of having neurodevelopmental sequelae. Previous studies reveal that the offspring of diabetic mothers exhibit disturbances in behavioral and intellectual functioning. In the examination of cognitive functioning, a poorer performance was observed in the children born to diabetic mothers when compared with the children of non-diabetic mothers. Therefore, it is important to study the possible effects of maternal diabetes on the hippocampus of these infants.
{"title":"The Impact of Diabetes on Hippocampus","authors":"S. Vafaei-Nezhad, Masood Vafaei-Nezhad, Mehri Shadi, Samira Ezi","doi":"10.5772/intechopen.99895","DOIUrl":"https://doi.org/10.5772/intechopen.99895","url":null,"abstract":"Maternal Diabetes is one of the most common metabolic disorders resulting an increased risk of abnormalities in the developing fetus and offspring. It is estimated that the prevalence of diabetes during pregnancy among women in developing countries is approximately 4.5 percent and this range varies between 1 to 14 percent in different societies. According to earlier studies, diabetes during pregnancy is associated with an increased risk of maternal and child mortality and morbidity as well as major congenital anomalies including central nervous system (CNS) in their offspring. Multiple lines of evidence have suggested that infants of diabetic women are at risk of having neurodevelopmental sequelae. Previous studies reveal that the offspring of diabetic mothers exhibit disturbances in behavioral and intellectual functioning. In the examination of cognitive functioning, a poorer performance was observed in the children born to diabetic mothers when compared with the children of non-diabetic mothers. Therefore, it is important to study the possible effects of maternal diabetes on the hippocampus of these infants.","PeriodicalId":169305,"journal":{"name":"Hippocampus - New Advances [Working Title]","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127488114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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