Biomedical subjects

C S Young-Chan

Publications and source records attributed to C S Young-Chan.

3 recordsLinked to original sources

PubMed2000

Transforming growth factor-beta1 induces transforming growth factor-beta1 and transforming growth factor-beta receptor messenger RNAs and reduces complement C1qB messenger RNA in rat brain microglia.

Transforming growth factor-beta1 is a multifunctional peptide with increased expression during Alzheimer's disease and other neurodegenerative conditions which involve inflammatory mechanisms. We examined the autoregulation of transforming growth factor-beta1 and transforming growth factor-beta receptors and the effects of transforming growth factor-beta1 on complement C1q in brains of adult Fischer 344 male rats and in primary glial cultures. Perforant path transection by entorhinal cortex lesioning was used as a model for the hippocampal deafferentation of Alzheimer's disease. In the hippocampus ipsilateral to the lesion, transforming growth factor-beta1 peptide was increased >100-fold; the messenger RNAs encoding transforming growth factor-beta1, transforming growth factor-beta type I and type II receptors were also increased, but to a smaller degree. In this acute lesion paradigm, microglia are the main cell type containing transforming growth factor-beta1, transforming growth factor-beta type I and II receptor messenger RNAs, shown by immunocytochemistry in combination with in situ hybridization. Autoregulation of the transforming growth factor-beta1 system was examined by intraventricular infusion of transforming growth factor-beta1 peptide, which increased hippocampal transforming growth factor-beta1 messenger RNA levels in a dose-dependent fashion. Similarly, transforming growth factor-beta1 increased levels of transforming growth factor-beta1 messenger RNA and transforming growth factor-beta type II receptor messenger RNA (IC(50), 5pM) and increased release of transforming growth factor-beta1 peptide from primary microglia cultures. Interactions of transforming growth factor-beta1 with complement system gene expression are also indicated, because transforming growth factor-beta1 decreased C1qB messenger RNA in the cortex and hippocampus, after intraventricular infusion, and in cultured glia. These indications of autocrine regulation of transforming growth factor-beta1 in the rodent brain support a major role of microglia in neural activities of transforming growth factor-beta1 and give a new link between transforming growth factor-beta1 and the complement system. The auto-induction of the transforming growth factor-beta1 system has implications for transgenic mice that overexpress transforming growth factor-beta1 in brain cells and for its potential role in amyloidogenesis.

Alzheimer Disease↗

PubMed1996

Perforant path transection induces complement C9 deposition in hippocampus.

The presence of complement system proteins in amyloid plaques and the up-regulation of several complement mRNAs in neurons and glial cells in affected brain regions during Alzheimer disease (AD) provided a basis for further examination of complement protein expression in a rodent lesion model of AD. Perforant path transection in rats was used as a model for the degeneration of entorhinal cortex (EC) layer II neurons and the consequent deafferentation of the hippocampus that occurs during AD. Immunostaining for C9, a key terminal component of the complement cascade membrane attack complex (MAC), showed extracellular C9 deposition in parenchyma around the EC wound and in hippocampus as early as 1 day, and disappeared by 14 days postlesion. Apoptosis of EC layer II neurons was seen and was presumably due to severing of their axonal projections to the hippocampus by the transection lesion. However, apoptotic EC layer II neurons were not immunostained by anti-rat C9 antibody, suggesting complement was not involved in inducing apoptosis. In the deafferented hippocampus, extracellular C9 immunostaining was localized to the dentate gyrus middle molecular layer, a region of synaptic loss, dendritic degeneration, and early synaptogenesis. In addition, intracellular C9 immunostaining was seen only in select hippocampal interneurons. Dentate gyrus granule neurons and pyramidal neurons were not C9 immunostained. Clusterin (SGP-2), a soluble inhibitor of the MAC that is up-regulated in AD, was also detected in the wound area (extracellular), the dentate gyrus middle molecular layer (extracellular), and intracellularly in scattered hippocampal interneurons. The data support the hypothesis that the complement system generally participates in responses to brain injury, as well as in AD.

Afferent Pathways↗

PubMed1994

Transforming growth factor-beta 1 induces neuronal and astrocyte genes: tubulin alpha 1, glial fibrillary acidic protein and clusterin.

Transforming growth factor-beta 1 was studied as a possible regulator of messenger RNAs in astrocytes and neurons that increase after hippocampal deafferentation by perforant path transection: tubulin alpha 1, clusterin and glial fibrillary acidic protein messenger RNA. Because transforming growth factor-beta 1 messenger RNA is increased after this lesion, we examined which messenger RNA lesion responses could be induced by transforming growth factor-beta 1 alone. Porcine transforming growth factor-beta 1 infused into the lateral ventricle elevated the messenger RNAs for tubulin alpha 1, clusterin and glial fibrillary acidic protein 24 h after infusion in the ipsilateral hippocampus. As assayed by nuclear run-on, the transcription of glial fibrillary acidic protein RNA was increased in the ipsilateral hippocampus after perforant path transection and in primary rat astrocyte cultures by transforming growth factor-beta 1. In contrast, transforming growth factor-beta 1 did not change apolipoprotein-E messenger RNA or transcription, or growth associated protein-43 messenger RNA levels. We conclude that transforming growth factor-beta 1 increases subsets of neuronal and astrocyte messenger RNAs coding for cytoskeletal proteins that are also elevated in response to experimental lesions and Alzheimer's disease. This suggests that transforming growth factor-beta 1 might be a local organizing factor of neuronal and astrocyte responses to brain injury.

Animals↗