ABSTRACT
5-Hydroxytryptamine (5-HT) type 3 receptor (5-HT3R) is the only type of ligand-gated ion channel in the 5-HT receptor family. Through the high permeability of Na+, K+, and Ca2+ and activation of subsequent voltage-gated calcium channels (VGCCs), 5-HT3R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system (CNS). 5-HT3Rs are widely expressed in the medial prefrontal cortex (mPFC), amygdala (AMYG), hippocampus (HIP), periaqueductal gray (PAG), and other brain regions closely associated with anxiety reactions. They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions. 5-HT3Rs mediate the activation of the cholecystokinin (CCK) system in the AMYG, and the γ-aminobutyric acid (GABA) "disinhibition" mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons (IINs). In contrast, a 5-HT3R-induced GABA "disinhibition" mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects. 5-HT2R-mediated regulation of anxiety reactions are also activated by 5-HT3R-activated 5-HT release in the HIP and PAG. This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT3Rs. However, given the circuit specific modulation of 5-HT3Rs on emotion, systemic use of 5-HT3R agonism or antagonism alone seems unlikely to remedy anxiety, which deeply hinders the current clinical application of 5-HT3R drugs. Therefore, the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.
Subject(s)
Serotonin , Receptors, Serotonin, 5-HT3 , Anxiety , Neurons , gamma-Aminobutyric AcidABSTRACT
Objective To investigate the prevention and treatment of delayed transverse myelitis caused by radiotherapy in patients with thoracic esophageal carcinoma . Methods Radical radiotherapy had been given to five patients (female 3,male 2) with thoracic esophageal carcinoma with delayed transverse myelitis developed 7 to 30 months after radiotherapy without any local recurrence.The study was done in an attempt to describe the clinical symptoms and signs.Analysis of causes was done to seek possible means of treatment and prevention.Results Once delayed transverse myelitis had happened,it was not possible to cure. In this group, four patients died 1-2 years after myelopathy had accurred , and one was alive with functional neurologic loss. Conclusions Delayed transverse myelitis is an uncommon and serious complication induced by irradiation. It is very difficult to manage and indicates a very poor prognosis. We recommend prucise radiation design and prudent performance for prevention.