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Repeated VU0155069 Treatment Is Associated with Region- and Pathological Stage-Specific Dendritic Spine Remodeling in Female 3xTg-AD Mice
Mohanty S, Bosworth S, Ramaswamy K, Natarajan C, Krishnan B.. bioRxiv, 2026-10-27
Topic: Disease mechanisms in lab and animal studies
Background Alzheimer’s disease (AD) is increasingly recognized as a disorder of synaptic integrity in which changes in dendritic spine abundance and morphology accompany progressive cognitive dysfunction. Phospholipase D1 (PLD1), a regulator of membrane trafficking and cytoskeletal signaling, is aberrantly elevated in AD-related pathological states (ADRD). Previous studies from our lab demonstrated that repeated VU0155069 treatment promotes functional resilience in female 3xTg-AD mice, including improvements in novel-object recognition, fear-conditioning performance, hippocampal LTP, later-stage LTP and LTD, selected neuropathological outcomes, and most importantly, CA1 spine integrity. Objective To determine how this previously demonstrated functional resilience is represented structurally across cortical, hippocampal, and amygdalar circuits at earlier and later stages of AD-like pathology. Methods Female 3xTg-AD mice received vehicle or VU0155069 at 1 mg/kg intraperitoneally every other day for one month beginning at 5 or 11 months of age, with Golgi-Cox analysis at 6 or 12 months, respectively. Age-matched vehicle-treated 3xTg-AD littermates served as the primary comparator for evaluating the structural response to pharmacological attenuation of disease-associated PLD1 signaling. Results Auditory and visual cortical fields showed selective changes in spine-subtype distribution and morphometry. Hippocampal cornu ammonis (CA)2, CA3, and dentate gyrus (DG) exhibited distinct patterns involving spine abundance, density, and geometry, whereas the central, lateral, and basolateral amygdalar nuclei showed nucleus- and stage-dependent remodeling. Across the multiregional dataset, recurring responses comprised spine-subtype redistribution, changes in spine abundance, and morphometric remodeling rather than uniform structural rescue. Conclusions VU0155069 engages circuit- and pathological stage-specific forms of dendritic spine remodeling across distributed recognition- and associative-memory networks. Graphical Abstract
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APA 7th
Mohanty, S., Bosworth, S., Ramaswamy, K., Natarajan, C., & Krishnan, B. (2026). Repeated VU0155069 Treatment Is Associated with Region- and Pathological Stage-Specific Dendritic Spine Remodeling in Female 3xTg-AD Mice. bioRxiv. https://doi.org/10.64898/2026.10.26.762038
Vancouver
Mohanty S, Bosworth S, Ramaswamy K, Natarajan C, Krishnan B. Repeated VU0155069 Treatment Is Associated with Region- and Pathological Stage-Specific Dendritic Spine Remodeling in Female 3xTg-AD Mice. bioRxiv. 2026. doi:10.64898/2026.10.26.762038.
BibTeX
@article{mohanty2026-916cd2ae,
author = {Mohanty, S. and Bosworth, S. and Ramaswamy, K. and Natarajan, C. and Krishnan, B.},
title = {{Repeated VU0155069 Treatment Is Associated with Region- and Pathological Stage-Specific Dendritic Spine Remodeling in Female 3xTg-AD Mice}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.10.26.762038},
url = {https://doi.org/10.64898/2026.10.26.762038}
}
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Key findings
- Previous studies from our lab demonstrated that repeated VU0155069 treatment promotes functional resilience in female 3xTg-AD mice, including improvements in novel-object recognition, fear-conditioning performance, hippocampal LTP, later-stage LTP and LTD, selected neuropathological outcomes, and most importantly, CA1 spine integrity.
- Objective To determine how this previously demonstrated functional resilience is represented structurally across cortical, hippocampal, and amygdalar circuits at earlier and later stages of AD-like pathology.
- Results Auditory and visual cortical fields showed selective changes in spine-subtype distribution and morphometry.
Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “3xtg”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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