The effects of acute and long-term lithium treatments on trkB neurotrophin receptor activation in the mouse hippocampus and anterior cingulate cortex.
As brain-derived neurotrophic factor (BDNF) and its receptor trkB are linked to the etiology and treatment of mood disorders, we examined the effects of acute and long-term treatment of mood-stabilizer lithium on trkB activation and signaling and BDNF levels in the mouse anterior cingulate cortex (AC) and hippocampus (HC). The trkB activity was measured using specific antibodies against the phosphorylated trkB catalytic domain (pY705/6) and the shc binding site (pY515). In the AC, both acute and long-term LiCl treatment enhanced the pY705/6 of trkB. In contrast, acute or long-term LiCl treatment did not significantly alter the pY705/6 of trkB in the HC. Interestingly, however, acute LiCl treatment significantly reduced the phosphorylation of cAMP related element binding protein (CREB), a major intracellular target of trkB, in the HC. Moreover, pY515 of trkB in the AC and HC was not altered by any of the treatment. Also, prolonged LiCl treatment had no significant effects on BDNF levels or CREB activation in either the AC or HC. The present results suggest that acute and long-term lithium treatment induces trkB activation in the AC but not in the HC. The activation of CREB is, however, significantly reduced in the HC after acute LiCl treatment.
Rantamäki
Tomi
T
Neuroscience Center, University of Helsinki, Finland.
Knuuttila
Juha E A
JE
Hokkanen
Marie-Estelle
ME
Castrén
Eero
E
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects / Q000502:physiology*; D006179:Gyrus Cinguli / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010750:Phosphoproteins / Q000378:metabolism; D020813:Receptor, trkB / Q000187:drug effects / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D010750:Phosphoproteins; D020813:Receptor, trkB; D018021:Lithium Chloride