Biomedical subjects

N Bayatti

Publications and source records attributed to N Bayatti.

4 recordsLinked to original sources

PubMed2002

Cyclic AMP differentially regulates the expression of fibroblast growth factor and epidermal growth factor receptors in cultured cortical astroglia.

Fibroblast growth factor (FGF)-2 and transforming growth factor alpha (TGFalpha) promote astroglial proliferation during brain development and reactive processes. The mitogenic potential of both growth factors is attenuated by increasing intracellular cAMP levels, an effect currently assumed to depend on the inhibition of the mitogen-activated protein kinase cascade. In the present study, we sought to determine whether cAMP interferes with the mitogenic potential of FGF-2 and TGFalpha on astroglia by affecting the expression of respective growth factor receptors. Treatment of highly enriched cultures of cortical astrocytes with dibutyryl cAMP accelerated the TGFalpha-induced internalization and subsequent functional inactivation of epidermal growth factor (EGF) receptor by transiently inhibiting EGF receptor mRNA synthesis. In apparent contrast, both short- and long-term activation of cAMP-dependent signaling pathways robustly promoted the expression of FGF receptors 1 and 2, whereas expression levels of FGF receptor 3 remained unaffected. Moreover, elevation of intracellular cAMP levels did not prevent translocation of FGF receptor 1 to the cell nucleus, a mechanism thought to be essential for FGF-2-induced cell proliferation. We propose that cAMP controls the mitogenic effects of TGFalpha and FGF-2 on astroglial cells by distinctly different mechanisms. Whereas cAMP seems to interfere with the mitogenic effects of TGFalpha on astroglial cells by affecting both the expression level and signaling of the EGF receptor, the modulatory effects of cAMP on FGF-2-induced astroglial proliferation seem to solely result from an inhibition of FGF receptor-activated signaling pathways.

Animals↗

PubMed2001

Cyclic AMP modulates the response of central nervous system glia to fibroblast growth factor-2 by redirecting signalling pathways.

Fibroblast growth factor-2 (FGF-2) acts as both a potent mitogen and differentiation factor for CNS glia. In the present study, we provide evidence that intracellular cAMP determines the proliferation-differentiation decision of astroglia to FGF-2 by either facilitating FGF-2 signalling to extracellular signal-related protein kinase (ERK) or cAMP response element binding protein (CREB). Pharmacologically increasing intracellular cAMP levels in cultured cortical astroglia by treatment with dbcAMP or forskolin attenuated FGF-2-induced ERK phosphorylation and glial cell proliferation. Similarly, FGF-2-induced glial proliferation was attenuated in the presence of the MEK inhibitor, PD98059, thus, confirming a direct correlation between FGF-2-induced ERK activation and glial cell proliferation. On the other hand, increases in intracellular cAMP levels in cortical astroglia prolonged FGF-2-induced CREB phosphorylation and subsequently potentiated the cAMP response element-dependent transcription of the immediate early gene, c-fos. Moreover, the effects of cAMP on the time-course of FGF-2-dependent CREB phosphorylation were mimicked by PD98059, suggesting that the cAMP-induced redirection of FGF-2-signalling is linked to the RAF-MEK-ERK signalling pathway.

Animals↗

PubMed2000

Neurotrophins require distinct extracellular signals to promote the survival of CNS neurons in vitro.

Althoughthe neurotrophins BDNF and NT-3 have been recognized as potent survival factors for distinct neuronal populations in the peripheral nervous system, they seem to have only minor effects on the survival of CNS neurons. In the present study, we provide evidence that BDNF and NT-3 require distinct additional extracellular signals in order to effectively promote the survival of several established populations of target neurons in the CNS. In dissociated cell cultures of the embryonic rat mesencephalon, BDNF promoted dopaminergic cell survival only after a delay of several days. Even after prolonged cultivation, survival promoting effects were completely absent with NT-3. Irrespective of the cultivation time, survival promoting effects of both BDNF and NT-3 on dopaminergic neurons were induced or potentiated upon simultaneous depolarization of cultured mesencephalic cells with NMDA or upon activation of cAMP/PKA-dependent signaling pathways with dibutyryl cAMP. Dibutyryl cAMP (dbcAMP), but not NMDA, also potentiated or induced the survival promoting effects of BDNF and NT-3 on cultured cerebellar granule cells. None of these substances, either alone or in combination, affected the survival of cultured cortical neurons. However, cortical cell survival increased upon depolarization with elevated potassium; an effect known to involve the induction of an autocrine BDNF loop. In both cerebellar and mesencephalic neurons, but not in cortical neurons, dbcAMP also potentiated neurotrophin-induced c-fos response, indicating intimate cross-coupling of signaling pathways activated by these different factors. Together these findings suggest that in the CNS, neurotrophins preferentially promote the survival of functionally active neurons. Our findings further reveal that the neuronal response to neurotrophins is modulated in a brain region-specific manner.

Animals↗

PubMed1997

Brain-derived neurotrophic factor in human platelets.

A sensitive, capture enzyme-linked immunosorbent assay (CELISA) has been applied to the accurate and reproducible measurement of brain-derived neurotrophic factor (BDNF) protein in normal human blood platelets, a mean concentration of 1.03 +/- 0.04 ng (SEM)/mg of platelet protein being observed. The method, which requires only 10 ml blood, is now suitable for the investigation of a variety of clinical disorders.

Blood Platelets↗