To study the role of hippocampal neuronal TREK-1 in a lipopolysaccharide (LPS)-induced depression model, we injected AAV-hSyn-BFP (nCTL group) or AAV-hSyn-BFP-Cre (nCre group) virus into the hippocampus of Cd-TREK-1 KD mice.
Pharmacologically reversible mutations of TREK channels will help to clarify the importance of these channels in pathophysiological conditions such as pain and depression.
Interestingly, sortilin physically interacts with the two pore domain potassium channel TREK-1 and the PE as well as its synthetic analog spadin is able to block the activation of TREK-1 highlighting their role in the depression pathology.
Our results demonstrate that the TREK-1 expression and function are altered in the absence of sortilin confirming the importance of this channel in the regulation on the mood as a crucial target to treat depression.
These results suggest that TREK-1 could be a potential therapeutic target for treatment of bipolar disorders as well as depression, while TREK-2 is a target well suited for treatment of major depression.
The TWIK-related K<sup>+</sup> channel-1 (TREK-1) controls several major cellular responses involved in memory formation and is believed to participate in the development of depression, cerebral ischemia and blood-brain barrier dysfunction.
Therefore, we investigated the effects of the TREK1 ion channel inhibitor anandamide and the TRPC3/6 inhibitor norgestimate on microRNA expression and antidepressant effect in the mouse chronic mild stress (CMS) model of depression.
TREK1 knockout mice have impaired PUFA-mediated neuroprotection to ischemia, reduced sensitivity to volatile anesthetics, altered perception of pain, and a depression-resistant phenotype.
Similar to mice treated with selective serotonin reuptake inhibitors (SSRIs), TREK1 knockout mice are resistant to depression-like behavior and have elevated serotonin levels leading to speculation that TREK1 inhibition may contribute to the therapeutic effects of SSRIs.
Recently, the two-pore domain potassium channel TREK-1 has been identified as a new target in depression, and its antagonists might become effective antidepressants.
TREK1 knockout mice display impaired polyunsaturated fatty acid-mediated protection against brain ischemia, reduced sensitivity to volatile anesthetics, resistance to depression and altered perception of pain.
The mammalian K2P2.1 potassium channel (TREK-1, KCNK2) is highly expressed in excitable tissues, where it plays a key role in the cellular mechanisms of neuroprotection, anesthesia, pain perception, and depression.
The mammalian K2P2.1 potassium channel (TREK-1, KCNK2) is highly expressed in excitable tissues, where it plays a key role in the cellular mechanisms of neuroprotection, anesthesia, pain perception, and depression.
Recent in vivo studies have demonstrated that TREK1, the most thoroughly studied K(2P) channel, has a key role in the cellular mechanisms of neuroprotection, anaesthesia, pain and depression.