Down syndrome (DS) is a genetic disorder caused by the extra copy of chromosome 21, and it affects multiple systems and alters brain development and diverse degrees of intellectual disability. Amino acids and monoamine make the neurotransmitters seem to help neuronal development, including neuronal and glial proliferation. Recent studies show there are reductions in serotonin, gamma-aminobutyric acid,and taurine in the frontal cortex of fetal Down syndrome.
• Serotonin
The serotonergic system plays a vital role in integrating emotion, cognition and motor function. In Down syndrome patients, it is found that serotonin (5-HT) and its primary metabolite (5-HIAA) are significantly decreased in the caudate nucleus and temporal cortex. These findings may be relevant to the pathogenesis of Down syndrome and treatment of cognitive and non-cognitive features in Down syndrome.
• Gamma-aminobutyric Acids
GABA is linked to numerous neurological disorders because it is a primary inhibitory neurotransmitter for the central nervous system(CNS). GABAergic neurons are located in the hippocampus, thalamus, basal ganglia, hypothalamus and brainstem. Decreased concentration of GABA or dysfunction of GABA receptors may produce a feeling of anxiousness. The scientific paper has shown that it has been associated with child psychiatry diseases, including autism spectrum disorder major depressive disorder. So GABA receptor agonists are first-line therapy for those diseases. For Down Syndrome, GABAA receptor subunits which are α1, α3 and γ2 subunits, are mostly infected in the hippocampus of Down syndrome fetuses. It is hypothesised that increased levels of the amyloid precursor protein (APP) and particularly its neurotoxic β-amyloid load downregulate α3 subunits.
• Taurine
Taurine directly influences neurons and neuronal progenitor synthesis mainly via glycine GABA receptors. In Down syndrome patients, it is traditionally used for treatment. However, the actual mechanism for this treatment is not well established. It is hypothesised that in Down syndrome patients who suffer from dysregulation in calcium homeostasis and endoplasmic reticulum stress, taurine may play a therapeutic role in these dysfunctions.
In Sum Up
The exact pathological mechanisms underlying Down syndrome are still unclear. The scientific shreds of evidence have highlighted the molecular mechanism involved in neurotransmitters and neuromodulators, which may become a future, promising therapy to encounter the symptoms of Down syndrome. So, there is a needy for scientists to identify and develop a multifaceted treatment for Down syndrome.
References:
1. Whittle N, Sartori SB, Dierssen M, Lubec G, Singewald N. Fetal Down syndrome brains exhibit aberrant neurotransmitters critical for normal brain development. Paediatrics. 2007 Dec;120(6):e1465-71. doi: 10.1542/peds.2006-3448. Epub 2007 Nov 12. PMID: 17998315.
2.Chang H, Lee DH. Pleiotropic Effects of Taurine on Nematode Model for Down Syndrome. Adv Exp Med Biol. 2019;1155:429-442. doi: 10.1007/978-981-13-8023-5_40. PMID: 31468420.