Serotonin depletion can enhance the cerebrovascular responses induced by cortical spreading depression via the nitric oxide pathway

Abstract

Serotonin (5-HT) is an important neurotransmitter involved in the control of neural and vascular responses. 5-HT depletion can induce several neurological disorders, including migraines. Studies on a cortical spreading depression (CSD) migraine animal model showed that the cortical neurons sensitivity, vascular responses, and nitric oxide (NO) production were significantly increased in 5-HT depletion. However, the involvement of NO in the cerebrovascular responses in 5-HT depletion remains unclear. This study aimed to investigate the role of NO in the CSD-induced alterations of cerebral microvessels in 5-HT depletion. Rats were divided into four groups: control, control with L-NAME treatment, 5-HT depleted, and 5-HT depleted with L-NAME treatment. 5-HT depletion was induced by intraperitoneal injection with para-chlorophenylalanine (PCPA) 3 days before the experiment. The CSD was triggered by KCl application. After the second wave of CSD, N-nitro-l-arginine methyl ester (L-NAME) or saline was intravenously injected into the rats with or without L-NAME treatment groups, respectively. The intercellular adhesion molecules-1 (ICAM-1), cell adhesion molecules-1 (VCAM-1), and the ultrastructural changes of the cerebral microvessels were examined. The results showed that 5-HT depletion significantly increased ICAM-1 and VCAM-1 expressions in the cerebral cortex. The number of endothelial pinocytic vesicles and microvilli was higher in the 5-HT depleted group when compared to the control. Interestingly, L-NAME treatment significantly reduced the abnormalities observed in the 5-HT depleted group. The results of this study demonstrated that an increase of NO production is one of the mechanisms involved in the CSD-induced alterations of the cerebrovascular responses in 5-HT depletion.

The clinical efficiency of acupuncture in preventing migraine attacks and its effect on serotonin levels

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Study of neurovascular coupling during cold pressor test in patients with migraine

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Nitroglycerin increases serotonin transporter expression in rat spinal cord but anandamide modulated this effect

“…By using proteomic methods Chanrion et al showed that the 5-HTT interacts with the nNOS and they concluded that this physical association may make reciprocal modulation possible (Chanrion et al, 2007). It was also shown that the application of L-NAME (a nonspecific nNOS inhibitor) reduces the vascular abnormalities which are induced by the CSD-triggered 5-HT depletion, suggesting that NO production has a pivotal role in the CSD caused 5-HT depletion (Saengjaroentham et al, 2015). In addition, Harkin and co-workers showed that inhibition of NO synthase could be used as a strategy to raise the clinical efficacy of serotonergic antidepressants, enhancing the activity of the drug (Harkin et al, 2004).…”