The Gut-Brain Axis, BDNF, NMDA and CNS Disorders

Abstract

Gastro-intestinal (GI) microbiota and the 'gut-brain axis' are proving to be increasingly relevant to early brain development and the emergence of psychiatric disorders. This review focuses on the influence of the GI tract on Brain-Derived Neurotrophic Factor (BDNF) and its relationship with receptors for N-methyl-D-aspartate (NMDAR), as these are believed to be involved in synaptic plasticity and cognitive function. NMDAR may be associated with the development of schizophrenia and a range of other psychopathologies including neurodegenerative disorders, depression and dementias. An analysis of the routes and mechanisms by which the GI microbiota contribute to the pathophysiology of BDNF-induced NMDAR dysfunction could yield new insights relevant to developing novel therapeutics for schizophrenia and related disorders. In the absence of GI microbes, central BDNF levels are reduced and this inhibits the maintenance of NMDAR production. A reduction of NMDAR input onto GABA inhibitory interneurons causes disinhibition of glutamatergic output which disrupts the central signal-to-noise ratio and leads to aberrant synaptic behaviour and cognitive deficits. Gut microbiota can modulate BDNF function in the CNS, via changes in neurotransmitter function by affecting modulatory mechanisms such as the kynurenine pathway, or by changes in the availability and actions of short chain fatty acids (SCFAs) in the brain. Interrupting these cycles by inducing changes in the gut microbiota using probiotics, prebiotics or antimicrobial drugs has been found promising as a preventative or therapeutic measure to counteract behavioural deficits and these may be useful to supplement the actions of drugs in the treatment of CNS disorders.

Indole Tryptophan Metabolism and Cytokine S100B in Children with Attention-Deficit/Hyperactivity Disorder: Daily Fluctuations, Responses to Methylphenidate, and Interrelationship with Depressive Symptomatology

“…In addition to protein synthesis, tryptophan metabolism follows the following main branches. In the main branch (*90% or more of tryptophan metabolism), the oxidation by indoleamine-2,3dioxygenase (IDO) breaks the indole ring, resulting in the formation of kynurenine and metabolites (kynurenines), nicotinic acid, and nicotinamide adenine dinucleotide (NAD+) synthesis (Stone 2016). In the other branch, 3%-10% of tryptophan metabolism keeps the indole ring intact while producing chemical messengers such as the indoleamines, serotonin and melatonin, and the trace amine tryptamine and its derivatives.…”

Remote Sensing Between Liver and Intestine: Importance of Microbial Metabolites

“…Gut microbiota is also essential in maintaining the constitutive levels of brain-derived neurotrophic factor (BNDF) and the function of N-methyl-D-aspartate receptors (NMDARs) in the central nervous system, via changes in neurotransmitter function by affecting modulatory mechanisms such as the kynurenine pathway or actions of SCFAs in the brain (101). …”

Reliability and validity of a questionnaire for diagnosis of clinical gastric related vertigo: A Traditional Persian Medicine perspective and prevalence assessment

“…There is evidence of a relationship between the brain and stomach; types of gastric-related headaches have also been reported in addition to GRV (32). In recent studies, a relationship between the brain and the digestive tract has been considered though gut-brain axis, some diseases such as Alzheimer's disease (33), anxiety and depression (34), multiple sclerosis, autism, stress (35) and dementia (36) which are recently proposed "may begin in the gut". A noble questionnaire for assessing GRV with an acceptable reliability and validity was the first achievement of this study.…”