Related Experiment Video
Updated: Jul 21, 2025
11:10
Dissecting Cell-Autonomous Function of Fragile X Mental Retardation Protein in an Auditory Circuit by In Ovo Electroporation
Published on: July 6, 2022
2.3K
Defects in early synaptic formation and neuronal function in Prader-Willi syndrome
Shuhei Soeda1, Daiki Ito2, Tomoe Ogushi2
1Laboratory of Neurochemistry, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji Higashi, Kusatsu, Shiga, 525-8577, Japan. soeda05@fc.ritsumei.ac.jp.
Scientific Reports
|July 25, 2023
Summary
Prader-Willi syndrome (PWS) neurons show impaired synaptic formation and reduced neuronal excitability. These findings suggest potential neurodevelopmental defects in PWS, linked to downregulated SLITRK1.
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- Prader-Willi syndrome (PWS) is an epigenetic disorder linked to chromosome 15q11-q13 gene deficiencies.
- PWS is associated with neurodevelopmental and psychiatric conditions, including autism spectrum disorder.
- Previous studies showed aberrant differentiation and transcriptomic dysregulation in PWS patient-derived induced pluripotent stem cells (iPSCs).
Purpose of the Study:
- To investigate synaptic formation and function in neurons derived from PWS patient iPSCs.
- To identify specific molecular defects contributing to neuronal dysfunction in PWS.
Main Methods:
- RNA sequencing to identify downregulated genes in PWS neural stem cells (NSCs).
- Differentiation of iPSCs from PWS patients and single gene defect mutants into neurons.
- Analysis of pre- and postsynaptic markers (e.g., PSD-95) and neurite morphology.
- Measurement of neuronal excitability via membrane potential responses to K+ stimulation.
Main Results:
- SLITRK1 was identified as a downregulated gene in PWS NSCs.
- Neurons derived from PWS and mutant iPSCs exhibited significantly lower levels of pre- and postsynaptic markers compared to controls.
- PSD-95 puncta were decreased along neurites in PWS neurons.
- Neuronal excitability was significantly reduced in PWS and mutant neurons.
Conclusions:
- Downregulation of SLITRK1 and impaired synaptic development contribute to neuronal dysfunction in PWS.
- These synaptic and functional deficits in PWS neurons may underlie neurodevelopmental phenotypes observed in the syndrome.
- iPSC-derived neurons provide a valuable model for studying PWS neurobiology.
More Related Videos
Related Concept Videos
02:30Genomic Imprinting and Inheritance
34.7K
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
34.7K
01:29Biological Causes of Schizophrenia
103
Schizophrenia, a severe psychiatric disorder, arises from a complex interplay of biological factors, including genetic predisposition, structural brain abnormalities, neurotransmitter dysregulation, and developmental irregularities. These factors collectively contribute to the onset and progression of the disorder, which typically manifests in late adolescence or early adulthood.
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin...
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin...
103
01:33Pleiotropy
40.6K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
40.6K
01:27Psychosis: Pathophysiology of Schizophrenia and Other Psychotic Disorders
749
Schizophrenia is a neurodevelopmental disorder whose origins are rooted in complex genetic components. Despite our burgeoning understanding, the pathophysiology of this disorder remains incompletely deciphered.
Researchers have identified genetic factors that increase susceptibility to schizophrenia, underscoring the intricate interplay between genetics and environment in disease development. At the core of schizophrenia's pathophysiology is excessive dopaminergic neurotransmission within...
Researchers have identified genetic factors that increase susceptibility to schizophrenia, underscoring the intricate interplay between genetics and environment in disease development. At the core of schizophrenia's pathophysiology is excessive dopaminergic neurotransmission within...
749
01:30Neurulation
42.1K
Neurulation is the embryological process which forms the precursors of the central nervous system and occurs after gastrulation has established the three primary cell layers of the embryo: ectoderm, mesoderm, and endoderm. In humans, the majority of this system is formed via primary neurulation, in which the central portion of the ectoderm—originally appearing as a flat sheet of cells—folds upwards and inwards, sealing off to form a hollow neural tube. As development proceeds, the...
42.1K
01:20Inborn Errors of Metabolism
199
Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...
199