Molecular components underlying nongenomic thyroid hormone signaling in embryonic zebrafish neurons

<p>Abstract</p> <p>Background</p> <p>Neurodevelopment requires thyroid hormone, yet the mechanisms and targets of thyroid hormone action during embryonic stages remain ill-defined. We previously showed that the thyroid hormone thyroxine (T4) rapidly increases voltage-gated sodium current in zebrafish Rohon-Beard cells (RBs), a primary sensory neuron subtype present during embryonic development. Here, we determined essential components of the rapid T4 signaling pathway by identifying the involved intracellular messengers, the targeted sodium channel isotype, and the spatial and temporal expression pattern of the nongenomic αVβ3 integrin T4 receptor.</p> <p>Results</p> <p>We first tested which signaling pathways mediate T4's rapid modulation of sodium current (I_Na) by perturbing specific pathways associated with nongenomic thyroid hormone signaling. We found that pharmacological blockade of protein phosphatase 1 and the mitogen-activated protein kinase p38 isoform decreased and increased tonic sodium current amplitudes, respectively, and blockade of either occluded rapid responses to acute T4 application. We next tested for the ion channel target of rapid T4 signaling via morpholino knock-down of specific sodium channel isotypes. We found that selective knock-down of the sodium channel α-subunit Na_v1.6a, but not Na_v1.1la, occluded T4's acute effects. We also determined the spatial and temporal distribution of a nongenomic T4 receptor, integrin αVβ3. At 24 hours post fertilization (hpf), immunofluorescent assays showed no specific integrin αVβ3 immunoreactivity in wild-type zebrafish embryos. However, by 48 hpf, embryos expressed integrin αVβ3 in RBs and primary motoneurons. Consistent with this temporal expression, T4 modulated RB I_Naat 48 but not 24 hpf. We next tested whether T4 rapidly modulated I_Naof caudal primary motoneurons, which express the receptor (αVβ3) and target (Na_v1.6a) of rapid T4 signaling. In response to T4, caudal primary motoneurons rapidly increased sodium current peak amplitude 1.3-fold.</p> <p>Conclusion</p> <p>T4's nongenomic regulation of sodium current occurs in different neuronal subtypes, requires the activity of specific phosphorylation pathways, and requires both integrin αVβ3 and Na_v1.6a. Our <it>in vivo </it>analyses identify molecules required for T4's rapid regulation of voltage-gated sodium current.</p

Vascular Steal Syndrome, Optic Neuropathy, and Foreign Body Granuloma Reaction to Onyx-18 Embolization for Congenital Orbito-Facial Vascular Malformation.

A 34-year-old patient presented with a right orbito-facial mass since childhood, consistent with a congenital arteriovenous (AV) malformation. Prior to presentation, she had multiple incomplete surgical resections and embolizations with N-butyl acetyl acrylate and Onyx-18. The patient reported gradual, progressive vision loss shortly after Onyx-18 embolization. Five months after embolization, she presented with decreased vision, disfigurement and mechanical ptosis relating to a large subcutaneous mass affecting the medial right upper eyelid and forehead. Significant exam findings included a visual acuity of 20/400 (20/60 prior to embolization), an afferent pupillary defect, and optic disc pallor. MRI and angiography revealed a persistent AV malformation with feeders from the ophthalmic artery and an absent choroidal flush to the right eye. Pathology from surgical resection showed a significant foreign body giant cell reaction to the embolization material adjacent to the vessels. We suggest that an incomplete embolization with Onyx-18 may have caused vascular steal syndrome from the ophthalmic artery

A pilot study of heart rate variability biofeedback therapy in the treatment of perinatal depression on a specialized perinatal psychiatry inpatient unit

PURPOSE: Heart rate variability biofeedback (HRVB) therapy may be useful in treating the prominent anxiety features of perinatal depression. We investigated the use of this non-pharmacologic therapy among women hospitalized with severe perinatal depression. METHODS: Three questionnaires, the State Trait Anxiety Inventory (STAI), Warwick Edinburgh Mental Well-Being Scale (WEMWBS), and Linear Analog Self Assessment (LASA), were administered to fifteen women in a specialized inpatient perinatal psychiatry unit. Participants were also contacted by telephone after discharge to assess continued use of HRVB techniques. RESULTS: The use of HRVB was associated with an improvement in all three scales. The greatest improvement (−13.867, p<0.001 and −11.533, p<0.001) was among STAI scores. A majority (81.9%, n=9) of women surveyed by telephone also reported continued frequent use at least once per week, and over half (54.6%, n=6) described the use of HRVB techniques as very or extremely beneficial. CONCLUSIONS: The use of HRVB was associated with statistically significant improvement on all instrument scores, the greatest of which was STAI scores, and most women reported frequent continued use of HRVB techniques after discharge. These results suggest that HRVB may be particularly beneficial in the treatment of the prominent anxiety features of perinatal depression, both in inpatient and outpatient settings