Expression of tyrosine kinase A in the cerebral cortex of postnatal developing rat

Tyrosine kinase A (TrkA)is an essential component of the high affinity nerve growth factor (NGF) receptor necessary to the mediate the biological effects of the neurotrophins, NGF. This study examined the distribution of TrkA-immunoreactivity (IR)cells in the postnatal rat cerebral cortex and the changes that occur in postnatal development as a result of the expression of this protein. TrkA-IR was detected at postnatal day (PD)3, PD6, PD9 and PD15. Base upon their somatodendritic morphology, the most commonly labeled cell type was the pyramidal neurons. At PD3 and PD6, layer I, II, III and V was immunopositive for TrkA, at PD9, not only at layer I, II, III, and V but also at layer VI. At PD15, the TrkA-positive cells were distributed in all layers. These TrkA-positive cells were not detected at PD0. In contrast, there was significant increase in the percentage of cells exhibiting TrkA-IR with development and the highest level was detected at PD15. These results suggest that the cerebral cortex expresses TrkA strongly during the postnatal period. Moreover, the postnatal development-related increase in the expression of TrkA-cells shows that NGF may have a trophic effect on these cerebral cortex neurons from the postnatal period.

Distribution of trkA in cerebral cortex and diencephalon of the mongolian gerbil after birth

TrkA is essential components of the high-affinity NGF receptor necessary to mediate biological effects of the neurotrophins NGF. Here we report on the expression of trkA in the cerebral cortex and diencephalon of mongolian gerbils during postnatal development. The expression of trkA was identified by immunohistochemical method. In parietal cortex and piriform cortex, higher levels of trkA-IR (immunoreactivity) were detected at 3 days postnatal (P3) and at P9. Although trkA was not expressed till P3 in the parietal cortex, it was detectable at birth in the piriform cortex. Several regions, such as Layers I, IV & VI, did not show much expression. Layer I showed especially weak labeling. In the hippocampus, thalamus, and hypothalamus, higher levels of trkA-IR were detected at P6 and P12 than earlier days. But trkA was not expressed at birth in the hippocampus, at P3 in the reticular thalamic nucleus (Rt), or neonatally in the dorsomedial hypothalamic nucleus (DM). This data shows that expression of trkA is developmentally regulated and suggests that high affinity neurotrophin-receptors mediate a transient response to neurotrophines in the cerebral cortex and diencephalon during mongolian gerbil brain ontogeny.

Expression of the neurotrophin receptors Trk A and Trk B in adult human astrocytoma and glioblastoma.

Neurotrophins and their receptors of the Trk family play a critical role in proliferation, differentiation and survival of the developing neurons. There are reports on their expression in neoplasms too, namely, the primitive neuroectodermal tumours of childhood, and in adult astrocytic gliomas. The involvement of Trk receptors in tumour pathogenesis, if any, is not known. With this end in view, the present study has examined 10 tumour biopsy samples (identified as astrocytoma, pilocytic astrocytoma and glioblastoma) and peritumoral brain tissue of adult patients, for the presence of Trk A and Trk B receptors, by immunohistochemistry. The nature of the tumour samples was also confirmed by their immunoreactivity (IR) to glial fibrillary acidic protein. In the peritumoral brain tissue, only neurons showed IR for Trk A and Trk B. On the contrary, in the tumour sections, the IR to both receptors was localized in the vast majority of glia and capillary endothelium. There was an obvious pattern of IR in these gliomas: high levels of IR were present in the low-grade (type I and II) astrocytoma; whereas in the advanced malignant forms (WHO grade IV giant cell glioblastoma and glioblastoma multiforme) the IR was very weak. These findings suggest that Trk A and Trk B are involved in tumour pathogenesis, especially in the early stage, and may respond to signals that elicit glial proliferation, and thus contribute to progression towards malignancy.