MAPK activation in cerebellar basket cell terminals after harmaline treatment.
The mitogen-activated protein kinases (MAPKs) are a family of signal transduction mediators that regulate a number of cellular activities, including cell growth and proliferation, differentiation and survival, via phosphorylation (activation) of protein kinases. MAPKs are also recruited during synaptic plasticity and remodeling. In the present study we used Western blotting and immunohistochemistry to examine the effects of harmaline administration on the phosphorylation state of three MAPKs: the extracellular signal-regulated kinase (ERK1/2), c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK), and p38 MAPK. Harmaline is a tremorigenic drug known to induce enhanced and rhythmic firing of the inferior olive. In rats, synchronous activity of the inferior olive cells induced by harmaline administered for four days from postnatal day 9 to 12 resulted in prolonged maintenance of polyinnervation of Purkinje cells by climbing fibers (axons of olivary cells). Immunohistochemistry showed small but sustained cytoplasmic positivity to phospho-ERK in Purkinje cells and a strong signal for phospho-ERK in the "pinceaux," terminals of the interneuronal basket cells onto Purkinje cells. A similar pattern was observed for JNK/SAPK, while no changes in p38 were noticed. Thus, it was revealed that the activation of two members of the MAPK family in these inhibitory presynaptic terminals is also one consequence of synchronous olivary input to Purkinje cells known to affect developmental plasticity.
Milasin
Jelena
J
Rita Levi Montalcini Brain Repair Center, University of Turin, Italy. jelena_milasin@yahoo.com
Buffo
Annalisa
A
Carulli
Daniela
D
Andjus
Pavle
P
Strata
Piergiorgio
P
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002531:Cerebellum / Q000166:cytology* / Q000378:metabolism; D004789:Enzyme Activation; D006246:Harmaline / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009847:Olivary Nucleus / Q000166:cytology / Q000378:metabolism; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D000697:Central Nervous System Stimulants; D006246:Harmaline; D020928:Mitogen-Activated Protein Kinases