Journal
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
Volume 184, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2019.172738
Keywords
rTMS; Depression; Hippocampus; Endocannabinoids
Funding
- National Natural Science Foundation of China [81630032, 81571309]
- National Science and Technology Support Program of China [2015BAI13B00]
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The anti-depressant effect of repetitive transcranial magnetic stimulation (rTMS), a clinically-useful treatment for depression, is associated with changes to the endocannabinoid system (ECS). However, it is currently unknown whether different frequencies of rTMS alter the ECS differently. To test this, rats exposed to chronic unpredictable stress (CUS) were treated with rTMS at two different frequencies (5 (high) or 1 Hz (low), 1.26 Tesla) for 7 consecutive days. Twenty-four hours after the final rTMS treatment, we evaluated depressive-like behaviors and the expression of several synaptic proteins and ECS-related proteins in the hippocampus. In addition, we knocked-down diacylglycerol lipase alpha (DAGL alpha) and cannabinoid type 1 receptor (CB1R), two important components of the ECS, and measured depressive-like behaviors and synaptic protein expression following rTMS. Furthermore, we measured the expression levels of several components of the ECS system in hippocampal-derived astrocytes and neurons exposed to repetitive magnetic stimulation (rMS) with different parameters (5 or 1 Hz, 0.84 or 1.26 Tesla). Interestingly, we found that only high-frequency rTMS ameliorated depressive-like behaviors and normalized the expression of hippocampal synaptic proteins in CUS-treated rats; this effect was eliminated by knockdown of DAGL alpha or CB1R. Moreover, we found that rMS at 5 Hz increased the expression of DAGL alpha and CB1R in hippocampal astrocytes and neurons. Collectively, our results suggest that high-frequency rTMS exerts its anti-depressant effect by up-regulating DAGL alpha and CB1R.
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