Amyloid β protein impairs motor function via thromboxane A2 in the rat striatum

Yagami, Tatsurou; Takahara, Yukio; Ishibashi, Chiyomi; Sakaguchi, Gaku; Itoh, Naohiro; Ueda, Kazuki; Nakazato, Hitoshi; Okamura, Noboru; Hiramatsu, Yoshihiro; Honma, Teruki; Arimura, Akinori; Sakaeda, Toshiyuki; Katsuura, Goro

doi:10.1016/j.nbd.2004.04.013

Cited by 17 publications

(11 citation statements)

References 42 publications

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“…The ligand of TBXA2R establishes a link between NMDA excitotoxicity and TXA2 signalling. Interestingly, amyloid-β treatments also induce TXA2 production and are associated with neurodegeneration, which is, in turn, attenuated by TXA2 antagonists (Yagami et al , 2004). It is also important to mention that F2RL2, identified in the Alzheimer’s mice models but not completely validated in the human samples, is also associated with NMDA excitotoxicity and is necessary for the APC-mediated protection after NMDA treatments (Guo et al , 2004).…”

Section: Discussionmentioning

confidence: 99%

DNA methylation map of mouse and human brain identifies target genes in Alzheimer’s disease

Sánchez-Mut¹,

Aso²,

Panayotis³

et al. 2013

Brain

120

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The central nervous system has a pattern of gene expression that is closely regulated with respect to functional and anatomical regions. DNA methylation is a major regulator of transcriptional activity, and aberrations in the distribution of this epigenetic mark may be involved in many neurological disorders, such as Alzheimer’s disease. Herein, we have analysed 12 distinct mouse brain regions according to their CpG 5’-end gene methylation patterns and observed their unique epigenetic landscapes. The DNA methylomes obtained from the cerebral cortex were used to identify aberrant DNA methylation changes that occurred in two mouse models of Alzheimer’s disease. We were able to translate these findings to patients with Alzheimer’s disease, identifying DNA methylation-associated silencing of three targets genes: thromboxane A2 receptor (TBXA2R), sorbin and SH3 domain containing 3 (SORBS3) and spectrin beta 4 (SPTBN4). These hypermethylation targets indicate that the cyclic AMP response element-binding protein (CREB) activation pathway and the axon initial segment could contribute to the disease.

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Section: Discussionmentioning

confidence: 99%

DNA methylation map of mouse and human brain identifies target genes in Alzheimer’s disease

Sánchez-Mut¹,

Aso²,

Panayotis³

et al. 2013

Brain

120

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“…TP receptors play a role in stimulation of afferent neurons and activation of important cardiovascular and pulmonary vagal reflexes [58]. Unilateral injection of Aβ-enhanced apomorphine-induced circling ipsilaterally in rats and significantly elevated the level of TXA 2 , but TXA 2 receptor antagonists attenuated Aβ-enhanced circling behavior, and TXA 2 mediated the fibrillar Aβ-induced impairment of striatal motor function [22]. TXA 2 also mediates iron-overload cardiomyopathy by the TNF-α-associated calcineurin-nuclear factor of activated T cells (NFAT) signaling pathway [59].…”

Section: Discussionmentioning

confidence: 99%

“…Takechi et al [21] found a novel subtype of IP receptor which is expressed in neurons but not glial cells in the CNS and is clearly distinct from the peripheral subtype in terms of ligand specificity. TXA 2 also participates in the progress of fibrillar Aβ-induced extrapyramidal motor dysfunction in rat striatum [22]. Their expression manner and signaling pathways in the CNS are still unclear.…”

Section: Introductionmentioning

confidence: 99%

Time course change of COX2-PGI2/TXA2 following global cerebral ischemia reperfusion injury in rat hippocampus

Yang

Wang

et al. 2014

Behav Brain Funct

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BackgroundNeuroinflammation plays pivotal roles in the progression of cerebral ischemia injury. Prostaglandins (PGs) as the major inflammatory mediators in the brain participate in the pathophysiological processes of cerebral ischemia injury. Cyclooxygenase-2 (COX2) is the rate-limiting enzyme of PGs, and thus it is necessary to characterize of the expression patterns of COX2 and its downstream products at the same time in a cerebral ischemia/reperfusion (I/R) model.MethodsThe levels of prostacyclin (PGI2) and thromboxane (TXA2) and the expression of COX2 were detected in the rat hippocampus at different time points after reperfusion (30 min, 2 h, 6 h, 24 h, 48 h, 7 d, and 15 d).ResultsThe COX2 mRNA and protein expressions in hippocampus both remarkably increased at 30 min, and peaked at 7 d after global cerebral I/R compared with the sham-operated group. The level of PGI2 significantly increased at 2 h after reperfusion, with a peak at 48 h, but was still significantly higher than the sham-operated animals at 15 d. TXA2 level decreased at 30 min and 2 h after reperfusion, but significantly increased at 6 h and peaked at 48 h. PGI2/TXA2 ratio increased at 30 min after reperfusion, and peaked at 48 h compared with the sham-operated animals.ConclusionsI/R injury significantly increased the COX2 expression, PGI2 and TXA2 levels, and the PGI2/TXA2 ratio in rat hippocampus in a time-dependent manner. As a consequence, the increased PGI2 level and PGI2/TXA2 ratio may represent a physiological mechanism to protect the brain against the neuronal damage produced by I/R injury.

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“…TP stimulates PLC via Gq, and elevates [Ca 2+ ]i [93]. Neurotoxicity of TXA 2 has not yet been detected in in vitro [162] and in vivo [167] models. …”

Section: Thromboxane Amentioning

confidence: 98%

“…An elevated level of TXA 2 has been found in the postmortem brains of AD patients [55]. TXA 2 is suggested to be involved in the extrapyramidal motor dysfunction of patients with AD [167]. Patients with poststroke dementia more often show increased thromboxane biosynthesis than nondemented stroke patients [147].…”

Section: Thromboxane Amentioning

confidence: 99%

Cerebral Arachidonate Cascade in Dementia: Alzheimers Disease and Vascular Dementia

Yagami¹

2006

Self Cite

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Phospholipase A(2) (PLA(2)), cyclooxygenase (COX) and prostaglandin (PG) synthase are enzymes involved in arachidonate cascade. PLA(2) liberates arachidonic acid (AA) from cell membrane lipids. COX oxidizes AA to PGG(2) followed by an endoperoxidase reaction that converts PGG(2) into PGH(2). PGs are generated from astrocytes, microglial cells and neurons in the central nervous system, and are altered in the brain of demented patients. Dementia is principally diagnosed into Alzheimer's disease (AD) and vascular dementia (VaD). In older patients, the brain lesions associated with each pathological process often occur together. Regional brain microvascular abnormalities appear before cognitive decline and neurodegeneration. The coexistence of AD and VaD pathology is often termed mixed dementia. AD and VaD brain lesions interact in important ways to decline cognition, suggesting common pathways of the two neurological diseases. Arachidonate cascade is one of the converged intracellular signal transductions between AD and VaD. PLA(2) from mammalian sources are classified as secreted (sPLA(2)), Ca(2+)-dependent, cytosolic (cPLA(2)) and Ca(2+)-independent cytosolic PLA(2) (iPLA(2)). PLA(2) activity can be regulated by calcium, by phosphorylation, and by agonists binding to G-protein-coupled receptors. cPLA(2) is upregulalted in AD, but iPLA(2) is downregulated. On the other hand, sPLA(2) is increased in animal models for VaD. COX-2 is induced and PGD(2) are elevated in both AD and VaD. This review presents evidences for central roles of PLA(2)s, COXs and PGs in the dementia.

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Amyloid β protein impairs motor function via thromboxane A2 in the rat striatum

Cited by 17 publications

References 42 publications

DNA methylation map of mouse and human brain identifies target genes in Alzheimer’s disease

DNA methylation map of mouse and human brain identifies target genes in Alzheimer’s disease

Time course change of COX2-PGI2/TXA2 following global cerebral ischemia reperfusion injury in rat hippocampus

Cerebral Arachidonate Cascade in Dementia: Alzheimers Disease and Vascular Dementia

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