In vitro modulation of gamma amino butyric acid (GABA) receptor expression by bone marrow stromal cells.
Bone marrow stromal cells (BMSC) have the capability to undergo a change of morphology, reminiscent of neuronal cells, after exposure to an inductive medium. These induced BMSC-derived neuron-like (BDNL) cells express several neuronal markers, including Microtubule-Associated Protein Tau, Neurofilament M, and Nestin as revealed by immunocytochemistry analysis. To assess whether the induction process has possible functional relevance, we have focused our attention on the expression of neurotransmitter receptors. In particular, we show that the expression of GABA(A) subunits alpha1, beta2/3, epsilon and GABA(B1) mRNAs is greatly enhanced in BMSC by the induction treatment. Similar results were obtained from rat skin fibroblasts subjected to the same induction protocol, with the exception for the GABA(B2) transcript that was expressed only by BMSC and BDNL. The presence of both GABA(B1) and GABA(B2) subunits in BDNL cells suggests that functional GABA(B) receptors might be assembled: we indeed found that a functional GABA(B) receptor, negatively linked to cyclic AMP production, is expressed in BDNL. Therefore, we suggest that BMSC can be converted into cells equipped with appropriate receptors coupled to transduction mechanisms, potentially responding to a specific neurotransmitter.
Marcoli
Manuela
M
Dip. Medicina Sperimentale, Sezione di Farmacologia e Tossicologia, Università degli Studi di, Genova, Italy.
Candiani
Simona
S
Tonachini
Laura
L
Monticone
Massimiliano
M
Mastrogiacomo
Maddalena
M
Ottonello
Andrea
A
Cervetto
Chiara
C
Paluzzi
Paola
P
Maura
Guido
G
Pestarino
Mario
M
Cancedda
Ranieri
R
Castagnola
Patrizio
P
D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D003470:Culture Media; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D066298:In Vitro Techniques; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
D003470:Culture Media; D017931:DNA Primers; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D016875:tau Proteins; C061195:neurofilament protein M; D005576:Colforsin; D000242:Cyclic AMP