Neurotransmitters: The Critical Modulators Regulating Gut–Brain Axis

Abstract

Neurotransmitters including catecholamines and serotonin play a crucial role in maintaining homeostasis in the human body. Studies on these neurotransmitters mainly revolved around their role in the “fight or flight” response, transmitting signals across a chemical synapse and modulating blood flow throughout the body. However, recent research has demonstrated that neurotransmitters can play a significant role in the gastrointestinal (GI) physiology. Norepinephrine (NE), epinephrine (E), dopamine (DA), and serotonin have recently been a topic of interest because of their roles in the gut physiology and their potential roles in gastrointestinal and central nervous system pathophysiology. These neurotransmitters are able to regulate and control not only blood flow, but also affect gut motility, nutrient absorption, gastrointestinal innate immune system, and the microbiome. Furthermore, in pathological states such as inflammatory bowel disease (IBD) and Parkinson’s disease, the levels of these neurotransmitters are dysregulated, therefore causing a variety of gastrointestinal symptoms. Research in this field has shown that exogenous manipulation of catecholamine serum concentrations can help in decreasing symptomology and/or disease progression. In this review article, we discuss the current state-of-the-art research and literature regarding the role of neurotransmitters in regulation of normal gastrointestinal physiology, their impact on several disease processes, and novel work focused on the use of exogenous hormones and/or psychotropic medications to improve disease symptomology.

Parkinson’s Disease: From Pathogenesis to Pharmacogenomics

“…Hypoactivity of the dopaminergic and noradrenergic systems in the brain stem are related to non-motor and motor symptoms in PD [113,114]. Dysregulation of these neurotransmitters is also involved in a variety of gastrointestinal symptoms in PD [115], and all of them appear to contribute to neurotransmitter and autonomic dysfunctions in PD [113], including mechanisms of l -DOPA-induced dyskinesia [115,116] and cardiovascular dysautonomia [117]. Therefore, appropriate doses of Atremorine alone or in combination with low doses of conventional antiparkinsonian drugs [118] may benefit PD patients in whom the biosynthetic apparatus of the catecholaminergic system is damaged, including tyrosine hydroxylase (TH), the tetrahydrobiopterin (BH4) cofactor of TH, and the activity of the BH4-synthesizing enzyme, GTP cyclohydrolase I (GCHI), as well as the activities of aromatic l -amino acid decarboxylase (AADC, DOPA decarboxylase), DBH, and phenylethanolamine N -methyltransferase (PNMT), which synthesize dopamine, noradrenaline, and adrenaline, respectively [119].…”

Differential serotonergic modulation across the main and accessory olfactory bulbs

“…In the CNS, serotonin and its various receptors regulate a breadth of neuropsychological processes including mood, reward, aggression, appetite and memory (Roth, ; Roth & Xia, ; Mittal et al . ). The CNS serotonin system mainly originates from the brainstem raphe nuclei and projects to almost every part of the brain (Jacobs & Azmitia, ).…”

Succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism: an update on pharmacological and enzyme‐replacement therapeutic strategies

“…The degree to which each contribute to pathophysiology remains unknown. However, emerging new roles for GABA exist beyond that of inhibitory neurotransmitter, including neuro-endocrine effects along the gut-brain axis, autophagy, circadian rhythms, and others (Kilb 2012; Lakhani et al 2014; Chellappa et al 2016; Mittal et al 2017). These roles provide novel opportunities to explore pathomechanisms in SSADHD.…”