Evidence map›Paper›PMID 38110041›Full record

ArticleNeurobiology of disease2024

ALDH5A1-deficient iPSC-derived excitatory and inhibitory neurons display cell type specific alterations.

Wardiya Afshar-Saber, Nicole A Teaney, Kellen D Winden, Hellen Jumo, Xutong Shi, Gabrielle McGinty, Jed Hubbs, Cidi Chen, Itay Tokatly Latzer, Federico Gasparoli and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.2field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 18 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Wardiya Afshar-SaberRosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; FM Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Nicole A TeaneyRosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; FM Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Kellen D WindenRosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; FM Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Hellen JumoRosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; FM Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Xutong ShiWashington State University, Department of Pharmacotherapy, Spokane, WA, USA.
Gabrielle McGintyRosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; FM Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Jed HubbsRosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; FM Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Cidi ChenRosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; FM Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Human Neuron Core, Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Boston, MA, USA.
Itay Tokatly LatzerRosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Federico GasparoliDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Darius Ebrahimi-FakhariRosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; FM Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Elizabeth D ButtermoreRosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; FM Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Human Neuron Core, Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Boston, MA, USA.
Jean-Baptiste RoulletWashington State University, Department of Pharmacotherapy, Spokane, WA, USA.
Phillip L PearlRosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Mustafa SahinRosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; FM Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: Mustafa.sahin@childrens.harvard.edu.
Harvard University · USBoston Children's Hospital · USWashington State University Spokane · US

Funding

Viral ModuleP30EY012196 · NEI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ZHIGANG HE · 1998 to 2026
$21.3M
Toward better characterization and clinical trial readiness for targeting neuropsychiatric manifestations in PTEN pathogenic variantsU54NS092090 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI Darcy Krueger · 2014 to 2026
$20.1M
Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SCOTT Loren POMEROY, MUSTAFA SAHIN · 2021 to 2026
$9.4M
Natural History of Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD), a Heritable Disorder of GABA MetabolismR01HD091142 · NICHD · WASHINGTON STATE UNIVERSITY · PI Phillip Lawrence Pearl · 2018 to 2026
$5.3M
Mouse Neurodevelopmental Behavior CoreU54HD090255 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SAHIN, MUSTAFA · 2016 to 2020
$5.2M
Molecular Mechanisms of Neuronal Hyperactivity in Tuberous Sclerosis ComplexK08NS112598 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI WINDEN, KELLEN · 2020 to 2024
$963k
NEI NIH HHS P30 EY012196NICHD NIH HHS P50 HD105351NICHD NIH HHS R01 HD091142NICHD NIH HHS U54 HD090255NINDS NIH HHS K08 NS112598NINDS NIH HHS U54 NS092090
6 · The paper itself

Abstract

Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a neurometabolic disorder caused by ALDH5A1 mutations presenting with autism and epilepsy. SSADHD leads to impaired GABA metabolism and results in accumulation of GABA and γ-hydroxybutyrate (GHB), which alter neurotransmission and are thought to lead to neurobehavioral symptoms. However, why increased inhibitory neurotransmitters lead to seizures remains unclear. We used induced pluripotent stem cells from SSADHD patients (one female and two male) and differentiated them into GABAergic and glutamatergic neurons. SSADHD iGABA neurons show altered GABA metabolism and concomitant changes in expression of genes associated with inhibitory neurotransmission. In contrast, glutamatergic neurons display increased spontaneous activity and upregulation of mitochondrial genes. CRISPR correction of the pathogenic variants or SSADHD mRNA expression rescue various metabolic and functional abnormalities in human neurons. Our findings uncover a previously unknown role for SSADHD in excitatory human neurons and provide unique insights into the cellular and molecular basis of SSADHD and potential therapeutic interventions.

Indexed as

Amino Acid Metabolism, Inborn ErrorsInduced Pluripotent Stem CellsDevelopmental DisabilitiesFemalegamma-Aminobutyric AcidHumansMaleNeuronsSuccinate-Semialdehyde DehydrogenaseALDH5A1 protein, humangamma-Aminobutyric AcidSuccinate-Semialdehyde DehydrogenaseAutism spectrum disorderEpilepsyGABA metabolismMitochondrionStem cell derived neurons

Identifiers

PMID38110041
PMCPMC10843729
OpenAlexW4389833803

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.