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Gene/Protein
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Target Concepts:
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Query: UMLS:C0848237 (
acute stress
)
4,619
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Chronic stress can be a precipitating factor in the onset of depression. Lentiviral-mediated knockdown of
HCN1
protein expression and reduction of functional I
h
produce antidepressant behavior. However, whether h-channels are altered in an animal model of depression is not known. We found that perisomatic
HCN1
protein expression and I
h
-sensitive physiological measurements were significantly increased in dorsal but not in ventral CA1 region/neurons following chronic unpredictable stress (CUS), a widely accepted model for major depressive disorder. Cell-attached patch clamp recordings confirmed that perisomatic I
h
was increased in dorsal CA1 neurons following CUS. Furthermore, when dorsal CA1 I
h
was reduced by shRNA-
HCN1
, the CUS-induced behavioral deficits were prevented. Finally, rats infused in the dorsal CA1 region with thapsigargin, an irreversible inhibitor of the SERCA pump, exhibited anxiogenic-like behaviors and increased I
h
, similar to that observed following CUS. Our results suggest that CUS, but not
acute stress
, leads to an increase in perisomatic I
h
in dorsal CA1 neurons and that HCN channels represent a potential target for the treatment of major depressive disorder.
...
PMID:Perisomatic changes in h-channels regulate depressive behaviors following chronic unpredictable stress. 3025 6
Growing evidence suggests a possible link between hyperpolarization-activated cyclic nucleotide-gated nonselective cation (HCN) channels and depression. In a recent study published in
Molecular Psychiatry
, we first demonstrate that
I
h
(the membrane current mediated by HCN channels) and
HCN1
protein expression were increased in dorsal, but not in ventral, CA1 region following chronic, but not
acute stress
. This upregulation of
I
h
was restricted to the perisomatic region of CA1 neurons and contributed to a reduction of neuronal excitability. A reduction of
HCN1
protein expression in dorsal CA1 region before the onset of chronic unpredictable stress-induced depression was sufficient to provide resilient effects to chronic unpredictable stress. Furthermore, in vivo block of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) pumps, a manipulation known to increase intracellular calcium levels and upregulate
I
h
, produced anxiogenic-like behavior and an increase in
I
h
, similar to that observed in chronic unpredictable stress model of depression. Here, we share our view on (1) how the function and expression of
HCN1
channels are changed in the brain in a subcellular region-specific manner during the development of depression and (2) how a reduction of
HCN1
protein expression provides resilience to chronic stress.
...
PMID:A Possible Link Between HCN Channels and Depression. 2841 9
