Distribution of mRNAs encoding transforming growth factors‐β1, ‐2, and ‐3 in the intact rat brain and after experimentally induced focal ischemia

Abstract

Transforming growth factors-beta1 (TGF-beta1), -2, and -3 form a small group of related proteins involved in the regulation of proliferation, differentiation, and survival of various cell types. Recently, TGF-betas were also demonstrated to be neuroprotective. In the present study, we investigated their distribution in the rat brain as well as their expression following middle cerebral artery occlusion. Probes were produced for all types of TGF-betas, and in situ hybridization was performed. We demonstrated high TGF-beta1 expression in cerebral cortex, hippocampus, central amygdaloid nucleus, medial preoptic area, hypothalamic paraventricular nucleus, substantia nigra, brainstem reticular formation and motoneurons, and area postrema. In contrast, TGF-beta2 was abundantly expressed in deep cortical layers, dentate gyrus, midline thalamic nuclei, posterior hypothalamic area and mamillary body, superior olive, areas of monoaminergic neurons, spinal trigeminal nucleus, dorsal vagal complex, cerebellum, and choroid plexus, and a high level of TGF-beta3 mRNA was found in cerebral cortex, hippocampus, basal amygdaloid nuclei, lateral septal nucleus, several thalamic nuclei, arcuate and supramamillary nuclei, superior colliculus, superior olive, brainstem reticular formation and motoneurons, area postrema, and inferior olive. Focal brain ischemia induced TGF-betas with markedly different expression patterns. TGF-beta1 was induced in the penumbral region of cortex and striatum, whereas TGF-beta2 and -beta3 were induced in different layers of the ipsilateral cortex. The expression of the subtypes of TGF-betas in different brain regions suggests that they are involved in the regulation of different neurons and bind to different latent TGF-beta binding proteins. Furthermore, they might have subtype-specific functions following ischemic attack.

Transforming Growth Factor Beta in the Central Nervous System

“…The distribution pattern of TGF-βs established using immunohistochemistry at the protein level and by means of in situ hybridization histochemistry at the mRNA level (Vincze et al, 2010) was similar in several brain regions. TGF-β2 and β3 immunoreactivities were present constitutively in cerebral cortical layers II, III and V and their expression depended on the cortical layer rather than the areas within the cerebral cortex.…”

“…Furthermore, different regions of hippocampus, as well as widely distributed cells in the hypothalamus and amygdala contained both TGF-ß2 and ß3. Intense labeling of these isoforms was also described in brainstem monoaminergic neurons, and motor nuclei Vincze et al, 2010). In turn, the striatum, most thalamic nuclei, and the superior colliculus were almost devoid of TGF-β2 and ß3 mRNA and immunoreactivities.…”

“…The expressions of other isoforms are also enhanced albeit with a different pattern around a focal lesion. Following middle cerebral artery occlusion, TGF-β1 expression was elevated in the penumbra around the lesion site while TGF-β2 and 3 expressions showed increases in particular cortical layers throughout the ipsilateral cerebral cortex (Vincze et al, 2010).…”

“…The available data on the cell type specific expression of other TGF-β isoforms is scarce. However, their distributions suggest a dominant neuronal expression Vincze et al, 2010).…”

“…In the cerebellum, TGF-β2 was present in the Purkinje cell layer while TGF-β3 mRNA was absent in the cerebellum. In addition, the medial mamillary nucleus, the parafascicular thalamic nucleus and the choroid plexus expressed predominantly TGF-β2 while the reticular thalamic nucleus, the superior colliculus, and the inferior olive contained almost exclusively TGF-β3 mRNA (Vincze et al, 2010). An important future question is the type of cells that express TGF-β in the central nervous system.…”