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, 94 (19), 10391-6

The Type 2 Iodothyronine Deiodinase Is Expressed Primarily in Glial Cells in the Neonatal Rat Brain

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The Type 2 Iodothyronine Deiodinase Is Expressed Primarily in Glial Cells in the Neonatal Rat Brain

A Guadaño-Ferraz et al. Proc Natl Acad Sci U S A.

Abstract

Thyroid hormone plays an essential role in mammalian brain maturation and function, in large part by regulating the expression of specific neuronal genes. In this tissue, the type 2 deiodinase (D2) appears to be essential for providing adequate levels of the active thyroid hormone 3,5,3'-triiodothyronine (T3) during the developmental period. We have studied the regional and cellular localization of D2 mRNA in the brain of 15-day-old neonatal rats. D2 is expressed in the cerebral cortex, olfactory bulb, hippocampus, caudate, thalamus, hypothalamus, and cerebellum and was absent from the white matter. At the cellular level, D2 is expressed predominantly, if not exclusively, in astrocytes and in the tanycytes lining the third ventricle and present in the median eminence. These results suggest a close metabolic coupling between subsets of glial cells and neurons, whereby thyroxine is taken up from the blood and/or cerebrospinal fluid by astrocytes and tanycytes, is deiodinated to T3, and then is released for utilization by neurons.

Figures

Figure 1
Figure 1
Northern blot demonstrating the specificity of the cDNA template used for riboprobe preparation for detecting D2 mRNA. Each lane contained 25 μg of total RNA isolated from the brown adipose tissue of 4-week-old control rats (lanes a and b), or rats exposed to cold (4°C) for 8 hr (lanes c and d). The position of RNA size standards in kilobases is shown. Cy, cyclophilin.
Figure 2
Figure 2
In situ hybridization on sections of 15-day-old neonatal rat brain showing the regional distribution of D2 mRNA. All sections were taken in the coronal plane at the levels of the olfactory bulb (A); the septum (B); the globus pallidus (C); the anterior hippocampus (D); the caudal hypothalamus (E and F); the pons and cerebellum (G); and the midbrain (H) and (I). J utilized a sense probe and shows a coronal section at a level similar to that in B. All sections were exposed for 2 weeks with the exception of F, which was exposed for 1 week. The arrow in E points to a region of very high expression in the lower part of the third ventricle. The arrow in F points to the sharp transition in D2 expression occurring along the lining of the third ventricle. Aq, cerebral aqueduct; AON, anterior olfactory nucleus; Ce, cerebellum; cc, corpus callosum; CPu, caudate-putamen nucleus; Ctx, cerebral cortex; DG, dentate gyrus; GP, globus pallidus; H, hypothalamus; ic, internal capsule; LH, lateral hebenula; LV, lateral ventricle; ME, median eminence; MG, medial geniculate nucleus; OB, olfactory bulb; ON, olivary nucleus; Pir, piriform cortex; RF, rhinal fissure; S, septum; SC, superior collicullus; Th, thalamus; VCN, ventral cochlear nucleus; wm, white matter. Layers of the cerebral cortex are shown in Arabic numerals.
Figure 3
Figure 3
Dark- and bright-field images showing the distribution of silver grains after coating the hybridized sections with photographic emulsion. The sections were exposed for 20 days. Sections shown correspond to the main olfactory bulb [dark field (A); bright field (B)], the dentate gyrus [dark field (C); bright field (D)], the somatosensory cortex [dark field (E); bright field (F)], and the hypothalamus at the level of the median eminence and arcuate nucleus (dark field (G); bright field (H)]. Arc, arcuate nucleus; bv, blood vessel; epl, external plexiform layer; Gr, granular cell layer; ir, infundibular recess; ME, median eminence; mcl, mitral cell layer; mol, molecular layer; PT, pars tuberalis; pyr, pyramidal cell layer (CA1 field); sr, stratum radiatum; svl, subventricular layer; wm, white matter. In G the arrow points to the ventricular lining and the arrowhead points to an extremely high signal above the pars tuberalis. The corresponding bright-field image is shown in the Inset of H, with black arrowheads pointing to the silver grains of the photographic emulsion. Photomicrographs were taken with a 5× objective. (Bars = 200 μm.)
Figure 4
Figure 4
Localization of D2 mRNA in astrocytes and tanycytes. Tissue sections were immunostained for glial fibrillary acidic protein after in situ hybridization with the antisense D2 riboprobe, and the sections were coated with film emulsion and exposed for 20 days. (A) Immunopositive cells (astrocytes) of layer 1 of the cerebral cortex. Some silver grains can be observed in the cell bodies, but the majority are located along the cell processes (arrowheads). (B) Molecular layer of the dentate gyrus. Astrocyte fibers can be seen crossing this region. Hybridization grains (arrowheads) colocalized with the staining. (C) Lower part of the third ventricle (3V). Silver grains are seen on the cell bodies of tanycytes lining the ventricle and on the cellular processes crossing into the adjacent arcuate nucleus. (D) Lack of correlation between D2 mRNA (silver grains, arrows) and neuronal-specific enolase mRNA (blue spots) in the granular cell layer of the cerebellum. (E) Presence of D2 mRNA (silver grains, arrows) in GFAP-stained astrocytes of the granular layer of cerebellum. Photomicrographs were taken with a 40× (AC) or 63× (D and E) immersion objective. [Bars = 20 μm (AC) and 10 μm (D and E).]

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