Abstract
Background: According to current hypotheses, antidepressant drug action is the result
of adaptive changes in neuronal signaling mechanisms rather than a primary effect
on neurotransmitter transporters, receptors, or metabolic enzymes. Among the signaling
mechanisms involved, protein kinases and phosphorylation have been shown to be modified
by drug treatment. Presynaptic signaling (calcium/calmodulin-dependent protein kinase
II [CaMKII]) and the protein machinery regulating transmitter release have been implicated
in the action of these drugs.
Methods: We investigated the effect of S-adenosylmethionine (SAM), a compound with
putative antidepressant activity, on presynaptic CaMKII and its synaptic vesicle substrate
synapsin I. The activity of CaMKII was assayed in synaptic subcellular fractions prepared
from hippocampus (HI), frontal cortex (FCX), striatum (STR), and parieto-temporal
cortex.
Results: The kinase activity was increased after SAM treatment in the synaptic vesicle
fraction of HI (31.7%), FCX (35.9%), and STR (18.4%). The protein level of CaMKII
was also increased in synaptic vesicles of HI (40.4%). The synapsin I level was unchanged
in synaptic vesicles but markedly increased in synaptic cytosol of HI (75.8%) and
FCX (163.0%). No changes for both CaMKII and synapsin I level were found in homogenates,
suggesting that synaptic protein changes are not explained by an increase in total
level of proteins, but rather by translocation to nerve terminals.
Conclusions: Similar to typical antidepressant drugs, SAM induces changes in CaMKII
activity and increases synapsin I level in HI and FCX nerve terminals, suggesting
a modulatory action on transmitter release.
Keywords
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Article info
Publication history
Accepted:
April 16,
2001
Received in revised form:
March 14,
2001
Received:
October 16,
2000
Identification
Copyright
© 2001 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
