Avtor/Urednik     Mele, Tina; Čarman-Kržan, Marija; Jurič, Damijana Mojca
Naslov     Regulatory role of monoamine neurotransmitters in astrocytic NT-3 synthesis
Tip     članek
Vir     Int J Dev Neurosci
Vol. in št.     Letnik 28, št. 1
Leto izdaje     2009
Obseg     str. 13-9
ISSN     0736-5748
Jezik     eng
Abstrakt     Astrocytes actively control neuronal activity and synaptic transmission and by producing various neurotrophic factors represent an important local cellular source of trophic support in the normal and diseased brain. Our present study showed the ability of astrocytes to synthesize neurotrophin-3 (NT-3) and the active involvement of the monoamine neurotransmitters noradrenaline, adrenaline, dopamine, and serotonin, as well as basic intracellular second messenger systems, in the regulation of NT-3 production in neonatal rat cortical astrocytes. Using a new NT-3 specific enzyme-immunoassay, we showed that neonatal rat cortical and, for comparison, cerebellar astrocytes in primary culture can synthesize NT-3; the basal cellular content of NT-3 protein was 23.2+/-0.4pg NT-3/mg cell protein and 23.6+/-0.9pg NT-3/mg cell protein, respectively. The examined neurotransmitters, with the exception of serotonin, were able to potently and transiently increase NT-3 mRNA and NT-3 protein content; their maximal effects were dose- and time-dependent. Noradrenaline (1muM), adrenaline (1muM), and dopamine (100muM) showed a maximal increase in NT-3 cellular content after 6h treatment causing a 1.9-, 1.8- and 2.7-fold elevation, respectively. Prior to the observed increase in NT-3 protein levels, the examined catecholamines increased NT-3 mRNA levels with maximal effects observed after 1h (noradrenaline) and 2h (adrenaline and dopamine) of incubation causing 2.4-, 2.6- and 3-fold elevation, respectively. Screening different activators of basic intracellular second messenger systems for their influence on NT-3 synthesis revealed that forskolin (20muM), dibutyryl cAMP (dBcAMP) (100muM), as well as calcimycin (1muM) (Ca(2+) ionophore A23187) and phorbol 12-myristate 13-acetate (TPA) (100nM), markedly increased the cellular level of NT-3 protein. (Abs. trunc. at 2000 ch.)
Deskriptorji     ASTROCYTES
NERVE GROWTH FACTORS
NEUROTRANSMITTERS
NOREPINEPHRINE
EPINEPHRINE
DOPAMINE
SEROTONIN
POLYMERASE CHAIN REACTION
ENZYME-LINKED IMMUNOSORBENT ASSAY
CELLS, CULTURED
RATS, WISTAR