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1.
Int J Mol Sci ; 20(16)2019 Aug 16.
Article in English | MEDLINE | ID: mdl-31426329

ABSTRACT

It is widely known that the degeneration of neural circuits is prominent in the brains of Alzheimer's disease (AD) patients. The reciprocal connectivity of the medial septum (MS) and hippocampus, which constitutes the septo-hippocampo-septal (SHS) loop, is known to be associated with learning and memory. Despite the importance of the reciprocal projections between the MS and hippocampus in AD, the alteration of bidirectional connectivity between two structures has not yet been investigated at the mesoscale level. In this study, we adopted AD animal model, five familial AD mutations (5XFAD) mice, and anterograde and retrograde tracers, BDA and DiI, respectively, to visualize the pathology-related changes in topographical connectivity of the SHS loop in the 5XFAD brain. By comparing 4.5-month-old and 14-month-old 5XFAD mice, we successfully identified key circuit components of the SHS loop altered in 5XFAD brains. Remarkably, the SHS loop began to degenerate in 4.5-month-old 5XFAD mice before the onset of neuronal loss. The impairment of connectivity between the MS and hippocampus was accelerated in 14-month-old 5XFAD mice. These results demonstrate, for the first time, topographical evidence for the degradation of the interconnection between the MS and hippocampus at the mesoscale level in a mouse model of AD. Our results provide structural and functional insights into the interconnectivity of the MS and hippocampus, which will inform the use and development of various therapeutic approaches that target neural circuits for the treatment of AD.


Subject(s)
Alzheimer Disease/pathology , Hippocampus/pathology , Septum of Brain/pathology , Alzheimer Disease/genetics , Amyloid beta-Protein Precursor/genetics , Animals , Disease Models, Animal , Female , Hippocampus/metabolism , Humans , Male , Mice, Transgenic , Mutation , Neural Pathways/metabolism , Neural Pathways/pathology , Presenilin-1/genetics , Septum of Brain/metabolism
2.
Mol Biol Rep ; 46(4): 4225-4234, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31102152

ABSTRACT

Sirt1, also known as the longevity gene, is an NAD+-dependent class III histone deacetylase that has been extensively studied in multiple areas of research including cellular metabolism, longevity, cancer, autoimmunity, and immunity. However, little is known about the function of Sirt1 in B cells. This study aimed to investigate the role of Sirt1 in the expression pattern of mRNAs in the resting B cells of mice. CD19+ B cell-specific inducible Sirt1 knockout (KO) mice were divided into tamoxifen-treated Sirt1 KO group (S19T) or control group (S19). mRNAs extracted from resting B cells of both groups were analyzed for differentially expressed genes (DEG) using microarray. DEG analysis showed significant differential expression of 20 genes, of which Hspa1a and Hspa1b showed the highest fold change (FC) in S19T compared with S19 (p value < 0.01 and FC > 3). Further, Kyoto Encyclopedia of Genes and Genomes analysis identified pathways associated with diseases, organismal systems, and antigen processing and presentation. Additionally, the pathways known to involve Hspa1a and Hspa1b were also activated in the S19T group. On the other hand, after in vitro stimulation with lipopolysaccharide, cell viability and IgM production were significantly decreased in Sirt1 KO B cells, while expressions of TNF-α, IL-6, and IL-10 were increased. In summary, our study reveals that Sirt1 may maintain the quiescent state in resting B cells by suppressing the increase of Hspa1a and Hspa1b. This work provides a foundation for further studies on the functional roles of Sirt1 in B cells.


Subject(s)
B-Lymphocytes/metabolism , HSP70 Heat-Shock Proteins/genetics , Sirtuin 1/deficiency , Animals , B-Lymphocytes/physiology , Cell Survival , Female , HSP70 Heat-Shock Proteins/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sirtuin 1/genetics , Sirtuin 1/metabolism
3.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 3): i19, 2012 Mar 01.
Article in English | MEDLINE | ID: mdl-22412394

ABSTRACT

The group 5 mixed-metal telluride, Hf(0.78)Ti(0.22)Te(5) (hafnium titanium penta-telluride), is isostructural with the binary phases HfTe(5) and ZrTe(5) and forms a layered structure extending parallel to (010). The layers are made up from chains of bicapped metal-centered trigonal prisms and zigzag Te chains. The metal site (site symmetry m2m) is occupied by statistically disordered Hf [78.1 (5)%] and Ti [21.9 (5)%]. In addition to the regular Te-Te pair [2.7448 (13) Å] forming the short base of the equilateral triangle of the trigonal prism, an inter-mediate Te⋯Te separation [2.9129 (9) Å] is also found. The classical charge balance of the compound can be described as [M(4+)][Te(2-)][Te(2) (2-)][Te(2) (0)] (M = Hf, Ti). The individual metal content can vary in different crystals, apparently forming a random substitutional solid solution (Hf(1-x)Ti(x))Te(5), with 0.15 ≤ x ≤ 0.22.

4.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 9): i45, 2011 Sep 01.
Article in English | MEDLINE | ID: mdl-22065277

ABSTRACT

The crystal structure of the low-temperature form of synthetic naumannite [disilver(I) selenide], Ag(2)Se, has been reinvestigated based on single-crystal data. In comparison with previous powder diffraction studies, anisotropic displacement parameters are additionally reported. The structure is composed of Se layers and two crystallographically independent Ag atoms. One Ag atom lies close to the Se layer and is surrounded by four Se atoms in a distorted tetra-hedral coordination, while the second Ag atom lies between the Se layers and exhibits a [3 + 1] coordination defined by three close Se atoms, forming a trigonal plane, and one remote Se atom.

5.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 3): i24, 2011 Feb 12.
Article in English | MEDLINE | ID: mdl-21522232

ABSTRACT

The title compound, potassium diniobium vanadium phospho-rus deca-sulfide, KNb(1.75)V(0.25)PS(10), was obtained by reaction of the elements with a eutectic mixture of KCl/LiCl. It is isostructural with the quaternary KNb(2)PS(10), but the Nb sites are occupied by statistically disordered Nb (87.5%) and V (12.5%) atoms. The structure is composed of anionic (∞) (1)[M(2)PS(10)](-) chains (M = Nb/V) separated from each other by K(+) ions. The chain is composed of [MS(8)] distorted bicapped trigonal prisms and [PS(4)] tetra-hedra. There are no inter-chain bonding inter-actions. The crystal used for the X-ray analysis was a racemic twin.

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