Expression of latent transforming growth factor beta binding proteins in the rat brain

Abstract

Transforming growth factor-betas are expressed in the brain, have neuroprotective functions, and may be involved in the pathogenesis of neurodegenerative disorders. Their intracellular processing, secretion, and extracellular activation requires latent transforming growth factor-beta binding proteins (LTBPs) as demonstrated in peripheral organs. Here, we first report that the four types of LTBPs are expressed in the rat brain based on reverse-transcriptase polymerase chain reaction (RT-PCR) and that the subtypes have different topographical distributions based on in situ hybridization histochemistry. LTBP-1 has a high expression level in several brain regions including choroid plexus, cerebral cortex, medial amygdaloid nucleus, anteromedial and midline thalamic nuclei, medial preoptic area, arcuate and dorsomedial hypothalamic nuclei, superior olive, and area postrema. LTBP-3 and -4 are the most widely distributed LTBPs. Both are abundant in the cerebral cortex, cerebellum, hypothalamus, amygdala, brainstem motor nuclei, and area postrema. In addition, LTBP-3 mRNA is also abundant in the choroid plexus, globus pallidus, anterior and reticular thalamic nuclei, mamillary body, substantia nigra, red nucleus, pontine nuclei, some brainstem sensory nuclei, and reticular formation, while LTBP-4 is more abundant in the hippocampus and the parabrachial nuclei. In contrast, the expression of LTBP-2 is restricted to cerebral cortex, CA1 neurons of the hippocampus, and perifornical/lateral hypothalamic areas. The hypothalamic cells were identified by double in situ hybridization histochemistry as orexin-synthesizing neurons, demonstrating that LTBP expression can be very specifically regulated. Our data demonstrate that each type of LTBPs have highly distinct distributional patterns suggesting that the expression of LTBPs are specifically regulated in the brain.

TGF-β1 promotes cerebral cortex radial glia-astrocyte differentiation in vivo

“…Here, we report that activation of TGF-β1 pathwayled to a premature appearance of GFAP+ cells in different regions of the embryonic telencephalon, mainly, in the cingulate cortex, neuroepithelium related to the third ventricle, and also at the pial region of the preoptic area. Although it has been reported the expression of TGF-β isoforms and also its different roles in these regions (Bouret et al, 2004; Dobolyi and Palkovits, 2008; Srivastava et al, 2014), the role of TGF-β1 in dorsomedial area of the cerebral cortex, cingulate cortex, specifically on astrocyte differentiation, is poorly known.…”

Transforming Growth Factor Beta in the Central Nervous System

“…LTBP1 had considerable level of expression in only some brain regions including the choroid plexus, the cerebral cortex, the medial amygdaloid nucleus, the anteromedial and midline thalamic nuclei, the medial preoptic area, the arcuate and dorsomedial hypothalamic nuclei, the superior olive and the area postrema. LTBP2 expression was restricted to the cerebral cortex, the hippocampus, and the lateral hypothalamus (Dobolyi & Palkovits, 2008). Comparison of the distribution of TGF-β and LTBP subtypes suggested that all 3 isoforms of TGF-βs are co-expressed with LTBP3 in the brain.…”

“…The four types of LTBPs also had distinct distribution patterns in the brain based on the localization of their mRNAs (Dobolyi & Palkovits, 2008). The dominant form in the brain was LTBP3 while LTBP4 also had high level of expression in a variety of forebrain areas.…”

“…The choroid plexus, where TGF-β2 expression is dominant contains LTBP1 and 3. The inferior olive and the arcuate nucleus, brain areas with dominant TGF-β3 expression contain large amount of LTBP4 and LTBP1, respectively (Dobolyi & Palkovits, 2008). Nevertheless, further double labeling studies are needed to actually establish co-expression of different isoforms of TGF-βs and LTBPs in single cells of the nervous system.…”

Age and Time of Day Influences on the Expression of Transforming Growth Factor-Beta and Phosphorylated SMAD3 in the Mouse Suprachiasmatic and Paraventricular Nuclei

“…Latent TGF-␤ -binding proteins, regulators of TGF-␤ function, have also recently been described to be expressed in the rat hypothalamus, including the PVN [34] . Given strong circadian influences on pituitary function, it should not be too surprising then that a putative modulator of the hypothalamic-pituitary communication should be found to be expressed in a diurnal manner.…”