The Effects of Gadolinium-Based Contrast Agents on the Cerebellum: from Basic Research to Neurological Practice and from Pregnancy to Adulthood

Ariyani, Winda; Khairinisa, Miski Aghnia; Perrotta, Gaetano; Manto, Mario; Koibuchi, Noriyuki

doi:10.1007/s12311-017-0903-4

Cited by 7 publications

(4 citation statements)

References 39 publications

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“…Although most previous studies have used T 3 to examine TH-induced gene expression, T 4 and rT 3 may also play important roles. T 4 enhanced dendrite arborization of Purkinje cells ( 41 , 45 ). Cerebellar developmental defects such as impaired neurogenesis or delayed migration of granule cells can be rescued by T 4 or rT 3 but not T 3 ( 13 , 46 ).…”

Section: Discussionmentioning

confidence: 99%

Involvement of integrin αvβ3 in thyroid hormone-induced dendritogenesis

Ariyani

Miyazaki²,

Amano³

et al. 2022

Front. Endocrinol.

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Activation and/or modulation of the membrane-associated receptors plays a critical role in brain development. Thyroid hormone (TH) acts on both nuclear receptors (thyroid hormone receptor, TR) and membrane-associated receptors, particularly integrin αvβ3 in neurons and glia. Integrin αvβ3-mediated signal transduction mediates various cellular events during development including morphogenesis, migration, synaptogenesis, and intracellular metabolism. However, the involvement of integrin αvβ3-mediated TH action during brain development remains poorly understood. Thus, we examined the integrin αvβ3-mediated effects of TH (T3, T4, and rT3) in the neurons and astrocytes using primary cerebellar culture, astrocyte-enriched culture, Neuro-2A clonal cells, and co-culture of neurons and astrocytes. We found that TH augments dendrite arborization of cerebellar Purkinje cells. This augmentation was suppressed by knockdown of integrin αvβ3, as well as TRα and TRβ. A selective integrin αvβ3 antagonist, LM609, was also found to suppress TH-induced arborization. However, whether this effect was a direct action of TH on Purkinje cells or due to indirect actions of other cells subset such as astrocytes was not clarified. To further study neuron-specific molecular mechanisms, we used Neuro-2A clonal cells and found TH also induces neurite growth. TH-induced neurite growth was reduced by co-exposure with LM609 or knockdown of TRα, but not TRβ. Moreover, co-culture of Neuro-2A and astrocytes also increased TH-induced neurite growth, indicating astrocytes may be involved in neuritogenesis. TH increased the localization of synapsin-1 and F-actin in filopodia tips. TH exposure also increased phosphorylation of FAK, Akt, and ERK1/2. Phosphorylation was suppressed by co-exposure with LM609 and TRα knockdown. These results indicate that TRs and integrin αvβ3 play essential roles in TH-induced dendritogenesis and neuritogenesis. Furthermore, astrocytes-neuron communication via TR-dependent and TR-independent signaling through membrane receptors and F-actin are required for TH-induced neuritogenesis.

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Section: Discussionmentioning

confidence: 99%

Involvement of integrin αvβ3 in thyroid hormone-induced dendritogenesis

Ariyani

Miyazaki²,

Amano³

et al. 2022

Front. Endocrinol.

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“…Three scans are routinely performed on MS patients to detect lesions: gadolinium (Gd)-enhanced, T1-w, and T2-w MRI. Gd-enhanced MRI, which visualizes disruption of the BBB, can detect de novo lesions [ 48 ], although recent reports have raised pharmacokinetic concerns regarding its repeated use [ 49 , 50 ]. T1-w and T2-w MRI, which are sensitive to brain water and fat content, can visualize lesions not enhanced by Gd-enhanced conventional MRI.…”

Section: Discussionmentioning

confidence: 99%

CEST MRI and MALDI imaging reveal metabolic alterations in the cervical lymph nodes of EAE mice

Thomas

Yang

Smith

et al. 2022

J Neuroinflammation

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Background Multiple sclerosis (MS) is a neurodegenerative disease, wherein aberrant immune cells target myelin-ensheathed nerves. Conventional magnetic resonance imaging (MRI) can be performed to monitor damage to the central nervous system that results from previous inflammation; however, these imaging biomarkers are not necessarily indicative of active, progressive stages of the disease. The immune cells responsible for MS are first activated and sensitized to myelin in lymph nodes (LNs). Here, we present a new strategy for monitoring active disease activity in MS, chemical exchange saturation transfer (CEST) MRI of LNs. Methods and results We studied the potential utility of conventional (T2-weighted) and CEST MRI to monitor changes in these LNs during disease progression in an experimental autoimmune encephalomyelitis (EAE) model. We found CEST signal changes corresponded temporally with disease activity. CEST signals at the 3.2 ppm frequency during the active stage of EAE correlated significantly with the cellular (flow cytometry) and metabolic (mass spectrometry imaging) composition of the LNs, as well as immune cell infiltration into brain and spinal cord tissue. Correlating primary metabolites as identified by matrix-assisted laser desorption/ionization (MALDI) imaging included alanine, lactate, leucine, malate, and phenylalanine. Conclusions Taken together, we demonstrate the utility of CEST MRI signal changes in superficial cervical LNs as a complementary imaging biomarker for monitoring disease activity in MS. CEST MRI biomarkers corresponded to disease activity, correlated with immune activation (surface markers, antigen-stimulated proliferation), and correlated with LN metabolite levels.

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“…Following administration, GBCA is deposited in several organs, including the brain 20 . This deposition may affect not only neurons but also astrocytes 21 – 23 .…”

Section: Introductionmentioning

confidence: 99%

Gadolinium-based contrast agent accelerates the migration of astrocyte via integrin αvβ3 signaling pathway

Ariyani

Miyazaki

Tsushima

et al. 2022

Sci Rep

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Gadolinium (Gd)-based contrast agents (GBCAs) are chemicals injected intravenously during magnetic resonance imaging to enhance the diagnostic yield. Repeated use of GBCAs causes their deposition in the brain. Such deposition may affect various neuronal cells, including astrocytes. In this study, we examined the effect of GBCAs (Omniscan, Magnescope, Magnevist, and Gadovist) on astrocyte migration, which is critical for formation of neurons during development and maintaining brain homeostasis. All GBCAs increased cell migration and adhesion with increased actin remodelling. Knockdown of integrin αvβ3 by RNAi or exposure to integrin αvβ3 inhibitor reduced astrocyte migration. GBCAs increased phosphorylation of downstream factors of αvβ3, such as FAK, ERK1/2, and Akt. The phosphorylation of all these factors were reduced by RNAi or integrin αvβ3 inhibitor. GBCAs also increased the phosphorylation of their downstream factor, Rac1/cdc42, belonging to the RhoGTPases family. Coexposure to the selective RhoGTPases inhibitors, decreased the effects of GBCAs on cell migration. These findings indicate that GBCAs exert their action via integrin αvβ3 to activate the signaling pathway, resulting in increased astrocyte migration. Thus, the findings of the study suggest that it is important to avoid the repeated use of GBCAs to prevent adverse side effects in the brain, particularly during development.

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The Effects of Gadolinium-Based Contrast Agents on the Cerebellum: from Basic Research to Neurological Practice and from Pregnancy to Adulthood

Abstract: Gadolinium (Gd)-based contrast agents (GBCAs) are used in magnetic resonance imaging (MRI) to increase the diagnostic yield.

Cited by 7 publications

References 39 publications

Involvement of integrin αvβ3 in thyroid hormone-induced dendritogenesis

Involvement of integrin αvβ3 in thyroid hormone-induced dendritogenesis

CEST MRI and MALDI imaging reveal metabolic alterations in the cervical lymph nodes of EAE mice

Gadolinium-based contrast agent accelerates the migration of astrocyte via integrin αvβ3 signaling pathway

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