Knock-in of Mutated hTAU Causes Insulin Resistance, Inflammation and Proteostasis Disturbance in a Mouse Model of Frontotemporal Dementia.

Abstract:

:Diabetes and obesity have been implicated as risk factors for dementia. However, metabolic mechanisms and associated signalling pathways have not been investigated in detail in frontotemporal dementia. We therefore here characterised physiological, behavioural and molecular phenotypes of 3- and 8-month-old male tau knock-in (PLB2TAU) vs wild-type (PLBWT) mice. Homecage analysis suggested intact habituation but a dramatic reduction in exploratory activity in PLB2TAU mice. Deficits in motor strength were also observed. At 3 months, PLB2TAU mice displayed normal glucose handling but developed hyperglycaemia at 8 months, suggesting a progressive diabetic phenotype. Brain, liver and muscle tissue analyses confirmed tissue-specific deregulation of metabolic and homeostatic pathways. In brain, increased levels of phosphorylated tau and inflammation were detected alongside reduced ER regulatory markers, overall suggesting a downregulation in essential cellular defence pathways. We suggest that subtle neuronal expression of mutated human tau is sufficient to disturb systems metabolism and protein handling. Whether respective dysfunctions in tauopathy patients are also a consequence of tau pathology remains to be confirmed, but could offer new avenues for therapeutic interventions.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Hull C,Dekeryte R,Koss DJ,Crouch B,Buchanan H,Delibegovic M,Platt B

doi

10.1007/s12035-019-01722-6

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

539-550

issue

1

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-019-01722-6

journal_volume

57

pub_type

杂志文章
  • Delayed Treatment with Green Tea Polyphenol EGCG Promotes Neurogenesis After Ischemic Stroke in Adult Mice.

    abstract::(-)-Epigallocatechin-3‑gallate (EGCG), the predominant constituent of green tea, has been demonstrated to be neuroprotective against acute ischemic stroke. However, the long-term actions of EGCG on neurogenesis and functional recovery after ischemic stroke have not been identified. In this study, C57BL/6 mice underwen...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-9924-0

    authors: Zhang JC,Xu H,Yuan Y,Chen JY,Zhang YJ,Lin Y,Yuan SY

    更新日期:2017-07-01 00:00:00

  • Distribution of Alox15 in the Rat Brain and Its Role in Prefrontal Cortical Resolvin D1 Formation and Spatial Working Memory.

    abstract::Docosahexaenoic acid (DHA) is enriched in membrane phospholipids of the central nervous system (CNS) and has a role in aging and neuropsychiatric disorders. DHA is metabolized by the enzyme Alox15 to 17S-hydroxy-DHA, which is then converted to 7S-hydroperoxy,17S-hydroxy-DHA by a 5-lipoxygenase, and thence via epoxy in...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-017-0413-x

    authors: Shalini SM,Ho CF,Ng YK,Tong JX,Ong ES,Herr DR,Dawe GS,Ong WY

    更新日期:2018-02-01 00:00:00

  • Regulation of gap junction coupling in the developing neocortex.

    abstract::In the developing mammalian, neocortex gap junctions represent a transient, metabolic, and electrical communication system. These gap junctions may play a crucial role during the formation and refinement of neocortical synaptic circuitries. This article focuses on two major points. First, the influence of gap junction...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/BF02755590

    authors: Rörig B,Sutor B

    更新日期:1996-06-01 00:00:00

  • Heme Oxygenase-1 and Carbon Monoxide Regulate Growth and Progression in Glioblastoma Cells.

    abstract::In human glioma tumours, heme oxygenase-1 (HO-1) is overexpressed when compared with normal brain tissues and during oligodendroglioma progression. However, the molecular mechanisms mediated by HO-1 to promote glioblastoma remain unknown. We therefore aimed at investigating the effect of HO-1 expression and its select...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-01869-7

    authors: Castruccio Castracani C,Longhitano L,Distefano A,Di Rosa M,Pittalà V,Lupo G,Caruso M,Corona D,Tibullo D,Li Volti G

    更新日期:2020-05-01 00:00:00

  • The Gut Microbiome Alterations and Inflammation-Driven Pathogenesis of Alzheimer's Disease-a Critical Review.

    abstract::One of the most important scientific discoveries of recent years was the disclosure that the intestinal microflora takes part in bidirectional communication between the gut and the brain. Scientists suggest that human gut microflora may even act as the "second brain" and be responsible for neurodegenerative disorders ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-018-1188-4

    authors: Sochocka M,Donskow-Łysoniewska K,Diniz BS,Kurpas D,Brzozowska E,Leszek J

    更新日期:2019-03-01 00:00:00

  • D-Galactose Causes Motor Coordination Impairment, and Histological and Biochemical Changes in the Cerebellum of Rats.

    abstract::Classical galactosemia is an inborn error of carbohydrate metabolism in which patients accumulate high concentration of galactose in the brain. The most common treatment is a galactose-restricted diet. However, even treated patients develop several complications. One of the most common symptoms is motor coordination i...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-9981-4

    authors: Rodrigues AF,Biasibetti H,Zanotto BS,Sanches EF,Schmitz F,Nunes VT,Pierozan P,Manfredini V,Magro DDD,Netto CA,Wyse ATS

    更新日期:2017-08-01 00:00:00

  • Different Degrees of Iodine Deficiency Inhibit Differentiation of Cerebellar Granular Cells in Rat Offspring, via BMP-Smad1/5/8 Signaling.

    abstract::Iodine deficiency (ID) during development results in dysfunction of the central nervous system (CNS) and affects psychomotor and motor function. It is worth noting that maternal mild and marginal ID tends to be the most common reason of preventable neurodevelopmental impairment, via a mechanism that has not been eluci...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9382-0

    authors: Dong J,Lei X,Wang Y,Wang Y,Song H,Li M,Min H,Yu Y,Xi Q,Teng W,Chen J

    更新日期:2016-09-01 00:00:00

  • Ethanol Activation of PKA Mediates Single-Minded 2 Expression in Neuronal Cells.

    abstract::Prenatal ethanol exposure can cause extensive apoptotic neurodegeneration throughout the developing central nervous system (CNS), which results in cognitive deficits and memory decline. However, the underlying mechanisms need further study. Single-minded 2 (Sim2), a transcriptional repressor, is reportedly involved in...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-8924-1

    authors: Wang X,Yang Z,Sun Y,Zhou H,Chu G,Zhang J,Meng X

    更新日期:2015-12-01 00:00:00

  • Simvastatin stimulates production of the antiapoptotic protein Bcl-2 via endothelin-1 and NFATc3 in SH-SY5Y cells.

    abstract::The use of statins for the prevention or treatment of different neurodegenerative diseases has generated considerable interest albeit with some controversy. Mechanisms of statin-induced neuroprotection are not well understood. Recently, we reported that simvastatin stimulated neuronal gene expression and protein level...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-010-8122-8

    authors: Butterick TA,Igbavboa U,Eckert GP,Sun GY,Weisman GA,Müller WE,Wood WG

    更新日期:2010-06-01 00:00:00

  • Increased oxidative stress and impaired antioxidant response in Lafora disease.

    abstract::Lafora disease (LD, OMIM 254780, ORPHA501) is a fatal neurodegenerative disorder characterized by the presence of glycogen-like intracellular inclusions called Lafora bodies and caused, in the vast majority of cases, by mutations in either EPM2A or EPM2B genes, encoding respectively laforin and malin. In the last year...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-8747-0

    authors: Romá-Mateo C,Aguado C,García-Giménez JL,Ibáñez-Cabellos JS,Seco-Cervera M,Pallardó FV,Knecht E,Sanz P

    更新日期:2015-01-01 00:00:00

  • Cell biology of the BLOC-1 complex subunit dysbindin, a schizophrenia susceptibility gene.

    abstract::There is growing interest in the biology of dysbindin and its genetic locus (DTNBP1) due to genetic variants associated with an increased risk of schizophrenia. Reduced levels of dysbindin mRNA and protein in the hippocampal formation of schizophrenia patients further support involvement of this locus in disease risk....

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-011-8183-3

    authors: Mullin AP,Gokhale A,Larimore J,Faundez V

    更新日期:2011-08-01 00:00:00

  • Amyloid-beta disrupts calcium and redox homeostasis in brain endothelial cells.

    abstract::In Alzheimer's disease, the accumulation of amyloid-beta (Aβ) in the brain occurs in the parenchyma and cerebrovasculature. Several evidences support that the neuronal demise is potentiated by vascular alterations in the early stages of the disease, but the mechanisms responsible for the dysfunction of brain endotheli...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-8740-7

    authors: Fonseca AC,Moreira PI,Oliveira CR,Cardoso SM,Pinton P,Pereira CF

    更新日期:2015-04-01 00:00:00

  • Neuroprotective Effects of Dehydroepiandrosterone Sulfate Through Inhibiting Expression of Matrix Metalloproteinase-9 from Bradykinin-Challenged Astroglia.

    abstract::Dehydroepiandrosterone sulfate (DHEAS), one of the most important neuroactive steroids, is produced in the adrenals and the brain. DHEAS is believed to play a critical role in modulating different forms of cellular control, including processes associated with human neural systems. Its production rate and level in seru...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-018-1125-6

    authors: Liou CJ,Yang CM,Lee TH,Liu PS,Hsieh HL

    更新日期:2019-01-01 00:00:00

  • Chondroitin Sulfate Impairs Neural Stem Cell Migration Through ROCK Activation.

    abstract::Brain injuries such as trauma and stroke lead to glial scar formation by reactive astrocytes which produce and secret axonal outgrowth inhibitors. Chondroitin sulfate proteoglycans (CSPG) constitute a well-known class of extracellular matrix molecules produced at the glial scar and cause growth cone collapse. The CSPG...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-017-0565-8

    authors: Galindo LT,Mundim MTVV,Pinto AS,Chiarantin GMD,Almeida MES,Lamers ML,Horwitz AR,Santos MF,Porcionatto M

    更新日期:2018-04-01 00:00:00

  • Guanosine Neuroprotection of Presynaptic Mitochondrial Calcium Homeostasis in a Mouse Study with Amyloid-β Oligomers.

    abstract::Amyloid-β oligomers (AβOs) toxicity causes mitochondrial dysfunction, leading to synaptic failure in Alzheimer's disease (AD). Considering presynaptic high energy demand and tight Ca2+ regulation, impairment of mitochondrial function can lead to deteriorated neural activity and cell death. In this study, an AD mouse m...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-02064-4

    authors: da Silva JS,Nonose Y,Rohden F,Lukasewicz Ferreira PC,Fontella FU,Rocha A,Brochier AW,Apel RV,de Lima TM,Seminotti B,Amaral AU,Galina A,Souza DO

    更新日期:2020-11-01 00:00:00

  • Comparative Mitochondrial-Based Protective Effects of Resveratrol and Nicotinamide in Huntington's Disease Models.

    abstract::Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent lysine deacetylase that regulates longevity and enhances mitochondrial metabolism. Both activation and inhibition of SIRT1 were previously shown to ameliorate neuropathological mechanisms in Huntington's disease (HD), a neurodegenerative disease...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-0048-3

    authors: Naia L,Rosenstock TR,Oliveira AM,Oliveira-Sousa SI,Caldeira GL,Carmo C,Laço MN,Hayden MR,Oliveira CR,Rego AC

    更新日期:2017-09-01 00:00:00

  • KU0063794, a Dual mTORC1 and mTORC2 Inhibitor, Reduces Neural Tissue Damage and Locomotor Impairment After Spinal Cord Injury in Mice.

    abstract::Autophagy is an intracellular catabolic mechanism for the degradation of cytoplasmic constituents in the autophagosomal-lysosomal pathway. This mechanism plays an important role in homeostasis and it is defective in certain diseases. Preceding studies have revealed that autophagy is developing as an important moderato...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-9827-0

    authors: Cordaro M,Paterniti I,Siracusa R,Impellizzeri D,Esposito E,Cuzzocrea S

    更新日期:2017-05-01 00:00:00

  • PLD3 in Alzheimer's disease.

    abstract::Rare coding variants in the phospholipase D3 (PLD3) gene, also known as HU-K4, have recently been identified to increase the risk for late-onset Alzheimer's disease (LOAD) by the whole exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large independent LOAD ca...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-014-8779-5

    authors: Wang J,Yu JT,Tan L

    更新日期:2015-04-01 00:00:00

  • MPTP Mouse Model of Preclinical and Clinical Parkinson's Disease as an Instrument for Translational Medicine.

    abstract::Parkinson's disease (PD) is characterized by the appearance of motor symptoms many years after the onset of neurodegeneration, which explains low efficiency of therapy. Therefore, one of the priorities in neurology is to develop an early diagnosis and preventive treatment of PD, based on knowledge of molecular mechani...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-017-0559-6

    authors: Mingazov ER,Khakimova GR,Kozina EA,Medvedev AE,Buneeva OA,Bazyan AS,Ugrumov MV

    更新日期:2018-04-01 00:00:00

  • Local accumulations of B-50/GAP-43 evoke excessive bleb formation in PC12 cells.

    abstract::B-50 (GAP-43) is an axonal, plasma membrane-associated protein involved in growth cone morphology and function. We have conducted immunocytochemical, electron microscopic, and time-lapse experiments to visualize morphological consequences of local accumulations of B-50 at the plasma membrane of B-50-transfected PC-B2 ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/BF02741362

    authors: Aarts LH,Verkade P,Schrama LH,Oestreicher AB,Gispen WH,Schotman P

    更新日期:1999-08-01 00:00:00

  • Visualization of the Breakdown of the Axonal Transport Machinery: a Comparative Ultrastructural and Immunohistochemical Approach.

    abstract::Axonal damage is a major factor contributing to disease progression in multiple sclerosis (MS) patients. On the histological level, acute axonal injury is most frequently analyzed by anti-amyloid precursor protein immunohistochemistry. To what extent this method truly detects axonal injury, and whether other proteins ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-018-1353-9

    authors: Rühling S,Kramer F,Schmutz S,Amor S,Jiangshan Z,Schmitz C,Kipp M,Hochstrasser T

    更新日期:2019-06-01 00:00:00

  • Vitamin B6 Reduces Neurochemical and Long-Term Cognitive Alterations After Polymicrobial Sepsis: Involvement of the Kynurenine Pathway Modulation.

    abstract::Neurological dysfunction as a result of neuroinflammation has been reported in sepsis and cause high mortality. High levels of cytokines stimulate the formation of neurotoxic metabolites by kynurenine (KYN) pathway. Vitamin B6 (vit B6) has anti-inflammatory and antioxidant properties and also acts as a cofactor for en...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-017-0706-0

    authors: Danielski LG,Giustina AD,Goldim MP,Florentino D,Mathias K,Garbossa L,de Bona Schraiber R,Laurentino AOM,Goulart M,Michels M,de Queiroz KB,Kohlhof M,Rezin GT,Fortunato JJ,Quevedo J,Barichello T,Dal-Pizzol F,Coimbra RS,

    更新日期:2018-06-01 00:00:00

  • Is hypercholesterolemia a risk factor for Alzheimer's disease?

    abstract::There is considerable attention being given to the association of Alzheimer's disease and cholesterol homeostasis. To that end, some have suggested that elevated cholesterol levels are a risk factor for Alzheimer's disease. If elevated cholesterol is a risk factor for Alzheimer's disease, then it would be expected tha...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1385/MN:31:1-3:185

    authors: Wood WG,Igbavboa U,Eckert GP,Johnson-Anuna LN,Müller WE

    更新日期:2005-01-01 00:00:00

  • Deficiency of Tenascin-C Alleviates Neuronal Apoptosis and Neuroinflammation After Experimental Subarachnoid Hemorrhage in Mice.

    abstract::Tenascin-C (TNC), a matricellular protein, is upregulated in brain parenchyma after experimental subarachnoid hemorrhage (SAH). Recent studies emphasize that early brain injury (EBI) should be overcome to improve post-SAH outcomes. The aim of this study was to investigate effects of TNC knockout (TNKO) on neuronal apo...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-018-1006-z

    authors: Liu L,Fujimoto M,Nakano F,Nishikawa H,Okada T,Kawakita F,Imanaka-Yoshida K,Yoshida T,Suzuki H

    更新日期:2018-11-01 00:00:00

  • Heat Shock Proteins Accelerate the Maturation of Brain Endothelial Cell Glucocorticoid Receptor in Focal Human Drug-Resistant Epilepsy.

    abstract::Pharmacoresistance in epilepsy is a major challenge to successful clinical therapy. Glucocorticoid receptor (GR) dysregulation can affect the underlying disease pathogenesis. We recently reported that local drug biotransformation at the blood-brain barrier is upregulated by GR, which controls drug-metabolizing enzymes...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-02043-9

    authors: Hossain M,Williams S,Ferguson L,Bingaman W,Ghosh A,Najm IM,Ghosh C

    更新日期:2020-11-01 00:00:00

  • Neuronal migration and the role of reelin during early development of the cerebral cortex.

    abstract::During development, neurons migrate to the cortex radially from periventricular germinative zones as well as tangentially from ganglionic eminences. The vast majority of cortical neurons settle radially in the cortical plate. Neuronal migration requires an exquisite regulation of leading edge extension, nuclear transl...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1385/MN:30:3:225

    authors: Jossin Y

    更新日期:2004-12-01 00:00:00

  • Statins, Bcl-2, and apoptosis: cell death or cell protection?

    abstract::Statins have proven their effectiveness in the treatment of cardiovascular disease. This class of drugs has also attracted attention as a potential treatment for dissimilar diseases such as certain types of cancers and neurodegenerative diseases. What appears to be a contradiction is that, in the case of cancer, it ha...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-013-8496-5

    authors: Wood WG,Igbavboa U,Muller WE,Eckert GP

    更新日期:2013-10-01 00:00:00

  • Are pheromones detected through the main olfactory epithelium?

    abstract::A major sensory organ for the detection of pheromones by animals is the vomeronasal organ (VNO). Although pheromones control the behaviors of various species, the effect of pheromones on human behavior has been controversial because the VNO is not functional in adults. However, recent genetic, biochemical, and electro...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-007-0014-1

    authors: Wang Z,Nudelman A,Storm DR

    更新日期:2007-06-01 00:00:00

  • The Motor KIF5C Links the Requirements of Stable Microtubules and IGF-1 Receptor Membrane Insertion for Neuronal Polarization.

    abstract::Three early signals of asymmetry have been described to occur in a single neurite of neurons at stage 2 of differentiation (before polarization) and shown to be essential for neuronal polarization: (i) accumulation of stable microtubules, (ii) enrichment of the plasma membrane with activatable IGF-1r, and (iii) polari...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-0144-4

    authors: Oksdath M,Guil AFN,Grassi D,Sosa LJ,Quiroga S

    更新日期:2017-10-01 00:00:00

  • Nuclear Factor-kappaB-Dependent Sestrin2 Induction Mediates the Antioxidant Effects of BDNF Against Mitochondrial Inhibition in Rat Cortical Neurons.

    abstract::Brain-derived neurotrophic factor (BDNF), in addition to its neurotrophic action, also possesses antioxidant activities. However, the underlying mechanisms remain to be fully defined. Sestrin2 is a stress-responsive gene implicated in the cellular defense against oxidative stress. Currently, the potential functions of...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9357-1

    authors: Wu CL,Chen SD,Yin JH,Hwang CS,Yang DI

    更新日期:2016-08-01 00:00:00