Lithium decreases secretion of Abeta1-42 and C-truncated species Abeta1-37/38/39/40 in chicken telencephalic cultures but specifically increases intracellular Abeta1-38.
We studied endogenous amyloid precursor protein (APP) processing and amyloid beta (Abeta) peptide formation in primary chicken telencephalic neurons, because their Abeta peptide sequence is identical to humans. As detected by quantitative Abeta-SDS-PAGE/immunoblot, Abeta peptides 1-40/42 and three additional C-truncated species, namely Abeta1-37/38/39 were regularly released into the supernatant. The highly conserved Abeta quintet strongly resembles the pattern of Abeta peptides found in human cerebrospinal fluid. Furthermore, the C-terminally shorter Abeta peptides 1-33/34 could be readily detected. Recent evidence indicates that lithium specifically inhibits secretion of the amyloidogenic Abeta1-42 peptide in cultured permanent cells transfected with human APP. We therefore investigated the effect of lithium on Abeta peptide secretion as well as intracellular Abeta peptides in our untransfected primary cell culture system. Our data shows that lithium leads to a dose-dependent reduction of Abeta1-37/38/39/40/42 secretion. Surprisingly, intracellular analysis revealed that lithium specifically increases a band comigrating with synthetic Abeta1-38 while Abeta1-40 and Abeta1-42 remained almost unaffected. These results demonstrate for the first time that lithium treatment decreases Abeta peptide secretion in primary chicken neuronal cells but specifically elevates intracellular Abeta1-38. Therefore, we conclude that there are two independent mechanisms of lithium in intra- and extracellular Abeta peptide production.
Esselmann
H
H
Department of Psychiatry, University of Göttingen, Göttingen, Germany.
Maler
J M
JM
Kunz
N
N
Otto
M
M
Paul
S
S
Lewczuk
P
P
Rüther
E
E
Kornhuber
J
J
Wiltfang
J
J
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004591:Electrophoresis, Polyacrylamide Gel; D015151:Immunoblotting; D008094:Lithium / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013687:Telencephalon / Q000187:drug effects / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D017077:Culture Media, Conditioned; D010446:Peptide Fragments; C078639:amyloid beta-protein (1-38); C075222:amyloid beta-protein (1-42); D008094:Lithium