Evidence map›Paper›PMID 40971297›Full record

ArticleCell reports2025

Dysregulation of astrocyte-secreted pleiotrophin contributes to neuronal structural and functional deficits in Down syndrome.

Ashley N Brandebura, Adrien Paumier, Quinn N Asbell, Tao Tao, Mariel Kristine B Micael, Sherlyn Sanchez, Nicola J Allen

Abstract read
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
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

11 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Astrocyte-driven multicellular mechanisms of CNS repair and cerebroprotection.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
  6. Article
  7. Astrocyte Reactivity by Alcohol Dependence in the Central Amygdala.bioRxiv : the preprint server for biology · 2026
    Article
  8. Article
  9. Article
  10. Article
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Ashley N BrandeburaThe Salk Institute for Biological Studies, Molecular Neurobiology Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: fsw8xt@virginia.edu.
Adrien PaumierThe Salk Institute for Biological Studies, Molecular Neurobiology Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Quinn N AsbellThe Salk Institute for Biological Studies, Molecular Neurobiology Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Tao TaoThe Salk Institute for Biological Studies, Molecular Neurobiology Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Mariel Kristine B MicaelUniversity of California, San Diego, Department of Psychology, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Sherlyn SanchezUniversity of California, San Diego, School of Biological Sciences, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Nicola J AllenThe Salk Institute for Biological Studies, Molecular Neurobiology Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: nallen@salk.edu.

Funding

Preparing Transfer Students for Research Careers in NeuroscienceR25NS119707 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Brenda L Bloodgood, ASHLEY LAUREN JUAVINETT · 2021 to 2026
$1.6M
Role of astrocyte-secreted pleiotrophin in dendritic spine phenotypes in Down SyndromeF32NS117776 · NINDS · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI BRANDEBURA, ASHLEY N · 2021 to 2022
$101k
NINDS NIH HHS F32 NS117776NINDS NIH HHS R25 NS119707
6 · The paper itself

Abstract

Neuronal dendrite patterning and synapse formation are tightly regulated during development to promote proper connectivity. Here, we identify downregulation of pleiotrophin, a secreted molecule enriched in astrocytes, as a major contributor to dendrite and synapse deficits in the Ts65Dn mouse model of Down syndrome (DS). We find overlapping deficits in neuronal dendrites and spines in Ts65Dn mutant and pleiotrophin knockout mice. We show that targeting pleiotrophin overexpression to astrocytes in adult Ts65Dn mice in vivo can rescue dendrite morphology as well as restore spine density, synapse number, and plasticity deficits in the hippocampus. Moreover, pleiotrophin promotes dendrite outgrowth in cultured Ts65Dn neurons through Alk-Akt signaling. Our findings highlight dysregulated astrocyte protein secretion as a contributing factor to DS and identify pleiotrophin as a plasticity-inducing molecule that can be used to promote proper circuit connectivity, importantly, at later stages of development after typical periods of circuit refinement have been completed.

Indexed as

AstrocytesCarrier ProteinsCytokinesDown SyndromeNeuronsAnimalsDendritesDendritic SpinesDisease Models, AnimalHippocampusHumansMiceMice, KnockoutSignal TransductionSynapsesCarrier ProteinsCytokinespleiotrophinastrocyteCP: Cell biologyCP: Neurosciencedendritedendritic spinesDown syndromehippocampusneurodevelopmental disorderpleiotrophinsynapsetrisomy 21visual cortex

Identifiers

PMID40971297
PMCPMC12591093

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.