Meet Dr. GPCR Summit Partners
- Click to Explore -
Assessing Serotonin 1A Receptor Expression and Function in Adult Fmr1 Knockout Mice, a Preclinical Model of Fragile X Syndrome*
- Dr. Tanishka Saraf -
- Mercer University College of Pharmacy -
- Atlanta, Georgia, USA -
Abstract
Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by neuronal hyperexcitability leading to intellectual disability, autism, seizures, sensory hypersensitivity, etc. Gi/o-coupled serotonin 1A receptors (5-HT1ARs) expressed on excitatory and inhibitory neurons modulate cellular excitation-inhibition. Recent preclinical and clinical studies have reported alterations in 5-HT1AR expression and function in autism. In this study, we evaluated the expression and function of 5-HT1ARs in adult, male Fmr1 knockout mice, a mouse model of FXS. Fmr1 knockout mice showed significantly higher whole brain 5-HT1AR expression than wild-type mice using [3H]5-CT saturation binding assay. This difference in expression disappeared with WAY-100635 (selective antagonist) treatment, confirming selective upregulation of 5-HT1ARs. A significantly higher 5-HT1AR expression was observed in the lateral septum and cortex of Fmr1 knockout mice relative to wild-type mice using [3H]5-CT autoradiography. In vivo, 8-OH-DPAT (2 mg/kg) significantly increased the prevalence of flat body posture and head weaving and decreased rearing in Fmr1 knockout mice compared to wild-type mice. The observed enhancement in responses to 5-HT1AR activation may be due to higher 5-HT1AR expression. Presently, there is no evidence that 5-HT1AR translation is regulated by fragile X mental retardation protein (FMRP) which is reduced or absent in FXS, however, changes in biosynthesis and presynaptic storage of 5-HT in a drosophila model of FXS, suggests central 5-HT system alterations caused by loss of FMRP.
About Dr. Tanishka Saraf
Tanishka Saraf is a Ph.D. student at the Department of Pharmaceutical Sciences at Mercer University College of Pharmacy. Her research focuses on evaluating and targeting serotonin receptors for therapeutic outcomes for epilepsy and seizures in Fragile X Syndrome. She is experienced in mouse behavioral assays, stereotaxic and perfusion surgeries, electroencephalography, colony management, autoradiography, radioligand binding assays, and immunohistochemistry. She is keen on understanding central nervous system disorders and developing safe, effective, and translationally valid treatments.
Author list and affiliations
-
Tanishka S. Saraf,
-
Yiming Chen,
-
Jessica L. Armstrong,
-
Clinton E. Canal
Mercer University College of Pharmacy
Dr. Tanishka Saraf on the web
Meet Dr. GPCR Summit Partners
- Click to Explore -
