Avtor/Urednik     Miklič, Špela; Jurič, Damijana Mojca; Čarman-Kržan, Marija
Naslov     Differences in the regulation of BDNF and NGF synthesis in cultured neonatal rat astrocytes
Tip     članek
Vir     Int J Dev Neurosci
Vol. in št.     Letnik 22, št. 3
Leto izdaje     2004
Obseg     str. 119-30
Jezik     eng
Abstrakt     Using a new brain-derived neurotrophic factor (BDNF) specific enzyme-immunoassay, we determined the basal cellular content of BDNF protein in neonatal rat astrocytes in primary culture, thus confirming the ability of astrocytes to synthesize BDNF in addition to nerve growth factor (NGF). We subsequently monitored the influence of different pharmacological agents: neurotransmitter receptor agonists, cytokines, and second messenger up-regulators, on the synthesis of BDNF and NGF. Marked differences in the regulation of their synthesis by the above pharmacological agents were observed in our study. The basal cellular levels of BDNF protein in cultured neonatal rat cortical and cerebellar astrocytes were 15.9 +-.3 and 18.7 +-.4 pg BDNF/mg cell protein, respectively, and differ significantly between astrocytes from different brain regions, whereas NGF levels were the same (16.1 ` 0.3 and 16.2 +-.7 pg NGF/mg cell protein, respectively). Screening different neurotransmitter systems for their influence on BDNF and NGF synthesis in cortical astrocytes revealed that dopamine (0.15 mM) is a potent up-regulator of BDNF protein synthesis in astrocytes, while kainic acid (50 microM) and histamine (1 microM) did not raise the cellular level of BDNF protein. Dopamine had no influence on NGF synthesis, while kainic acid caused minor, and histamine marked, elevation of NGF cellular content. Tumor necrosis factor-a (30 ng/ml) and interleukin-1beta (10 U/ml) treatments did not influence BDNF synthesis, whereas they markedly increased NGF protein cellular level. We also confirmed (using forskolin (20 microM) and phorbol 12-myristate 13-acetate (TPA) (100 nM)) that adenylate cyclase and protein kinase C participate in the downstream signaling responsible for the stimulation of BDNF synthesis, whereas in the regulation of NGF synthesis only the participation of protein kinase C was confirmed. (Abstract truncated at 2000 characters).
Deskriptorji     ASTROCYTES
NERVE GROWTH FACTORS
DOPAMINE
KAINIC ACID
HISTAMINE
TUMOR NECROSIS FACTOR
INTERLEUKIN-1
TETRADECANOYLPHORBOL ACETATE
ENZYME-LINKED IMMUNOSORBENT ASSAY
CELLS, CULTURED
RATS, WISTAR
ANIMALS, NEWBORN