Feasibility study for a downsized comparative thyroid assay with measurement of brain thyroid hormones and histopathology in rats: Case study with 6-propylthiouracil and sodium phenobarbital at high dose

Minami, Kenta; Suto, Hidenori; Sato, Akira; Ogata, Keiko; Kosaka, Toshio; Hojo, Hitoshi; Takahashi, Naofumi; Tomiyama, Naruto; Fukuda, Tomoko; Iwashita, Katsumasa; Aoyama, Hiroaki; Yamada, Tomoya

doi:10.1016/j.yrtph.2022.105283

Cited by 4 publications

(17 citation statements)

References 42 publications

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“…Highlighting these spatiotemporal dynamics, we previously reported that a transient maternal exposure to the propylthiouracil (PTU) resulted in the formation of a periventricular heterotopia in the developing rat brain (3,4). This malformation is not only inducible by anti-thyroid pharmaceuticals, but also by environmental thyroid disrupting chemicals in multiple strains of rats (3)(4)(5)(6)(7)(8)(9). The heterotopia is predominantly comprised of ectopic neurons and can be detected in 100% of pups following a 5-day perinatal exposure (gestational day 19postnatal day 2, GD19 -PN2) (4).…”

Section: Introductionmentioning

confidence: 99%

Thyroid hormone action controls multiple components of cell junctions at the ventricular zone in the newborn rat brain

O’Shaughnessy

McMichael²,

Sasser³

et al. 2023

Front. Endocrinol.

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Thyroid hormone (TH) action controls brain development in a spatiotemporal manner. Previously, we demonstrated that perinatal hypothyroidism led to formation of a periventricular heterotopia in developing rats. This heterotopia occurs in the posterior telencephalon, and its formation was preceded by loss of radial glia cell polarity. As radial glia mediate cell migration and originate in a progenitor cell niche called the ventricular zone (VZ), we hypothesized that TH action may control cell signaling in this region. Here we addressed this hypothesis by employing laser capture microdissection and RNA-Seq to evaluate the VZ during a known period of TH sensitivity. Pregnant rats were exposed to a low dose of propylthiouracil (PTU, 0.0003%) through the drinking water during pregnancy and lactation. Dam and pup THs were quantified postnatally and RNA-Seq of the VZ performed in neonates. The PTU exposure resulted in a modest increase in maternal thyroid stimulating hormone and reduced thyroxine (T4). Exposed neonates exhibited hypothyroidism and T4 and triiodothyronine (T3) were also reduced in the telencephalon. RNA-Seq identified 358 differentially expressed genes in microdissected VZ cells of hypothyroid neonates as compared to controls (q-values ≤0.05). Pathway analyses showed processes like maintenance of the extracellular matrix and cytoskeleton, cell adhesion, and cell migration were significantly affected by hypothyroidism. Immunofluorescence also demonstrated that collagen IV, F-actin, radial glia, and adhesion proteins were reduced in the VZ. Immunohistochemistry of integrin αvβ3 and isoforms of both thyroid receptors (TRα/TRβ) showed highly overlapping expression patterns, including enrichment in the VZ. Taken together, our results show that TH action targets multiple components of cell junctions in the VZ, and this may be mediated by both genomic and nongenomic mechanisms. Surprisingly, this work also suggests that the blood-brain and blood-cerebrospinal fluid barriers may also be affected in hypothyroid newborns.

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Section: Introductionmentioning

confidence: 99%

Thyroid hormone action controls multiple components of cell junctions at the ventricular zone in the newborn rat brain

O’Shaughnessy

McMichael²,

Sasser³

et al. 2023

Front. Endocrinol.

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“…In addition, the original CTA requires a considerable number of animals (20 pregnant rats per dose group per cohort, total 160 pregnant rats for 4-dose group study) ( USEPA, 2005 ), making adding other parameters practically difficult. Recently, to resolve such concerns, we proposed a modified CTA with additional parameters, such as examination of brain THs concentrations and brain histology as suggested previously ( Gilbert et al, 2024 , Gilbert et al, 2020 , Gilbert et al, 2021 , Gilbert et al, 2023 , O'Shaughnessy and Gilbert, 2020 ) but using reduced numbers of rats (10 maternal rats per dose group per cohort) ( Minami et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

“…We began verifying the feasibility, sensitivity and reliability of the modified CTA, and we have already shown that the modified CTA could detect 10 ppm 6-propylthiouracil (6-PTU)-induced severe (>70 %) suppression of serum THs in dams, with >50 % suppressed serum/brain TH concentrations in fetuses/pups and brain heterotopia in postnatal day (PND) 21 pups using step sections with grading ( Minami et al, 2023 ). 6-PTU is a potent thyroperoxidase (TPO)-inhibiting drug and also acts by inhibiting the enzyme deiodinase type 1 (D1), which converts T4 to its active form T3, resulting in TH disruption and altered brain development in rat studies ( Zoeller and Crofton, 2005 , O’Shaughnessy et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, for assessment of sensitivity of the modified CTA, since PB appears to exhibit the potential for TH disruption in pregnant animals and their offspring, its use as a reference chemical is valuable in strategic planning for testing many similar chemicals with TH disruption via liver enzyme induction. Therefore, in our previous verification study for the modified CTA, NaPB was selected as a second reference chemical together with 6-PTU ( Minami et al, 2023 ). However, as PB or NaPB is a highly neuroactive drug ( Dingemanse et al, 1989 , Lumley et al, 2021 ), it is likely to affect brain development ( Diaz and Schain, 1978 , Middaugh et al, 1981 ).…”

Section: Introductionmentioning

confidence: 99%

“…Significant hepatic enzyme up-regulation and mild but significant TH reductions were reported at 1200 ppm PB (T3 and T4 concentrations decreased 16–38 % and 18–28 % respectively ( Hood et al, 1999b ). Based on these findings, the dietary concentration of 1000 ppm NaPB was selected as a reference chemical for mild TH disruption in our previous study ( Minami et al, 2023 ). Consequently, our previous study confirmed that 1000 ppm NaPB induced mild suppression of serum THs in GD20 dams (T3 and T4 concentrations decreased by 24 % and 16 % respectively), no significant changes in serum T3, T4, or TSH in GD20 fetuses, and suppression of brain TH concentrations in male (33 %) and female (15 %) fetuses but not in male and female pups ( Minami et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

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Prenatal test cohort of a modified rat comparative thyroid assay adding brain thyroid hormone measurements and histology but lowering group size appears able to detect disruption by sodium phenobarbital

Minami,

Sato,

Tomiyama

et al. 2024

Current Research in Toxicology

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Enzymatic Electrochemical Biosensors for Neurotransmitters Detection: Recent Achievements and Trends

et al. 2023

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Neurotransmitters (NTs) play a crucial role in regulating the behavioral and physiological functions of the nervous system. Imbalances in the concentrations of NT have been directly linked to various neurological diseases (e.g., Parkinson’s, Huntington’s, and Alzheimer’s disease), in addition to multiple psychotic disorders such as schizophrenia, depression, dementia, and other neurodegenerative disorders. Hence, the rapid and real-time monitoring of the NTs is of utmost importance in comprehending neurological functions and identifying disorders. Among different sensing techniques, electrochemical biosensors have garnered significant interest due to their ability to deliver fast results, compatibility for miniaturization and portability, high sensitivity, and good controllability. Furthermore, the utilization of enzymes as recognition elements in biosensing design has garnered renewed attention due to their unique advantages of catalytic biorecognition coupled with simultaneous signal amplification. This review paper primarily focuses on covering the recent advances in enzymatic electrochemical biosensors for the detection of NTs, encompassing the importance of electrochemical sensors, electrode materials, and electroanalytical techniques. Moreover, we shed light on the applications of enzyme-based biosensors for NTs detection in complex matrices and in vivo monitoring. Despite the numerous advantages of enzymatic biosensors, there are still challenges that need to be addressed, which are thoroughly discussed in this paper. Finally, this review also presents an outlook on future perspectives and opportunities for the development of enzyme-based electrochemical biosensors for NTs detection.

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Feasibility study for a downsized comparative thyroid assay with measurement of brain thyroid hormones and histopathology in rats: Case study with 6-propylthiouracil and sodium phenobarbital at high dose

Cited by 4 publications

References 42 publications

Thyroid hormone action controls multiple components of cell junctions at the ventricular zone in the newborn rat brain

Thyroid hormone action controls multiple components of cell junctions at the ventricular zone in the newborn rat brain

Prenatal test cohort of a modified rat comparative thyroid assay adding brain thyroid hormone measurements and histology but lowering group size appears able to detect disruption by sodium phenobarbital

Enzymatic Electrochemical Biosensors for Neurotransmitters Detection: Recent Achievements and Trends

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