Alternative splicing in serotonergic system: Implications in neuropsychiatric disorders

  title={Alternative splicing in serotonergic system: Implications in neuropsychiatric disorders},
  author={Eva Latorre and Jos{\'e} Emilio Mesonero and Lorna W. Harries},
  journal={Journal of Psychopharmacology},
  pages={1352 - 1363}
Background: The serotonergic system is a key component of physiological brain function and is essential for proper neurological activity. Numerous neuropsychiatric disorders are associated with deregulation of the serotonergic system. Accordingly, many pharmacological treatments are focused on modulation of this system. While providing a promising line of therapeutic moderation, these approaches may be complicated due to the presence of alternative splicing events for key genes in this pathway… Expand
5 Citations
Aberrant alternative splicing of HTR2A exon II in peripheral blood lymphocytes of drug-naïve schizophrenic patients
Levels of HTR2A exon II transcript isoforms are upregulated in patients with schizophrenia, but at the same time, elevated expression level of the studied H TR2A transcripts is associated with fewer side effects of the therapy. Expand
Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management
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An Improved CRISPR/dCas9 Interference Tool for Neuronal Gene Suppression
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A systematic comparison of neurotoxicity of bisphenol A and its derivatives in zebrafish.
  • Jie Gu, Min Guo, +7 authors Guixiang Ji
  • Medicine
  • The Science of the total environment
  • 2021
It is deciphered that environmentally relevant concentrations of BPs exposure exhibited differential degrees of neurotoxicity, which ranked as below: BPAF > BPF ≈ BPA >-BPS. Expand


A functional alternative splicing mutation in human tryptophan hydroxylase-2
A common, but functional single-nucleotide polymorphism (SNP rs1386493) in the TPH2 gene is characterized, which decreases efficiency of normal RNA splicing, resulting in a truncated T PH2 protein (TPH2-TR) by alternative splicing. Expand
5-HT2C receptors in psychiatric disorders: A review
The development of drugs that specifically target 5-HT2C receptors will allow for better understanding of their involvement in the pathophysiology of psychiatric disorders including schizophrenia, anxiety, and depression and the development of agonists that could activate signal transduction pathways leading to better therapeutic efficiency with fewer adverse effects. Expand
Dissecting the role of the serotonin system in neuropsychiatric disorders using knockout mice
Mice lacking key components of the serotonin system have provided important animal models of genetic vulnerability to conditions such as anxiety disorders, aggression, and drug abuse and ongoing research with these mice may help elucidate the mechanistic functioning of this complex system. Expand
The activity of the serotonin receptor 2C is regulated by alternative splicing
The central nervous system-specific serotonin receptor 2C (5HT2C) controls key physiological functions, such as food intake, anxiety, and motoneuron activity, making it the target for antipsychotic drugs, appetite controlling substances, and possibly anti-spasm agents. Expand
Alternative Splicing and Extensive RNA Editing of Human TPH2 Transcripts
Results strongly suggest a complex fine-tuning of central nervous system 5-HT biosynthesis by TPH2 alternative splicing and RNA editing, involved in the etiology of psychiatric diseases, such as suicidal behaviour. Expand
Serotonergic neurotransmission manipulation for the understanding of brain development and function: Learning from Tph2 genetic models.
How the discovery of Tph2 has improved understanding on the role of serotonergic neurotransmission is described, and several association studies that have linked single nucleotide polymorphisms in the human TPH2 gene with behavioral disturbances and neuropsychiatric disorders are reported on. Expand
Brain serotonergic circuitries
The neuroanatomy and neurochemistry of brain serotonergic circuitries are described and it is argued that the specificity of the local chemocommunication between5-HT and other neuronal elements mainly depends on mechanisms regulating the extracellular concentration of 5-HT, the diversity of high-affinity membrane receptors, and their specific transduction modalities. Expand
Variations in tryptophan hydroxylase 2 linked to decreased serotonergic activity are associated with elevated risk for metabolic syndrome in depression
The findings suggest that TPH2 polymorphisms characterize a subgroup of depressed patients who are especially prone to develop metabolic disorders induced by a genotype-dependent impairment of serotonergic neurotransmission. Expand
Tryptophan hydroxylase-2: an emerging therapeutic target for stress disorders.
These findings reveal an active role of TPH2 in the stress response and provide new insights into the long recognized but not yet fully understood 5-HT-stress interaction. Expand
Tryptophan hydroxylase-2 (TPH2) in disorders of cognitive control and emotion regulation: A perspective
The genetic and neurobiological evidence is appraised to illustrate the critical role of TPH2 in central 5-HT system function and in the pathophysiology of a wide spectrum of disorders of cognitive control and emotion regulation, ranging from depression to attention-deficit/hyperactivity disorder. Expand