Evidence map›Paper›PMID 38014232›Full record

ArticlebioRxiv : the preprint server for biology2023

VTA dopamine neurons are hyperexcitable in 3xTg-AD mice due to casein kinase 2-dependent SK channel dysfunction.

Harris E Blankenship, Kelsey A Carter, Nina T Cassidy, Andrea N Markiewicz, Michael I Thellmann, Amanda L Sharpe, Willard M Freeman, Michael J Beckstead

Open access · greenAbstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Harris E BlankenshipAging and Metabolism Research Program, Oklahoma Medical Research Foundation.
Kelsey A CarterAging and Metabolism Research Program, Oklahoma Medical Research Foundation.
Nina T CassidyAging and Metabolism Research Program, Oklahoma Medical Research Foundation.
Andrea N MarkiewiczAging and Metabolism Research Program, Oklahoma Medical Research Foundation.
Michael I ThellmannAging and Metabolism Research Program, Oklahoma Medical Research Foundation.
Amanda L SharpeDepartment of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center.ORCID 0000-0003-3971-5946
Willard M FreemanGenes and Human Disease Research Program, Oklahoma Medical Research Foundation.ORCID 0000-0001-7027-999X
Michael J BecksteadAging and Metabolism Research Program, Oklahoma Medical Research Foundation.ORCID 0000-0002-1574-530X
Oklahoma Medical Research Foundation · USUniversity of Oklahoma Health Sciences Center · US

Funding

Targeted DNA Methylation and Mitochondrial Heteroplasmy CoreP30AG050911 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Michael T Kinter · 2015 to 2026
$13.9M
Sex divergence and cell specificity of age-related hippocampal DNA modificationsR01AG059430 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI FREEMAN, WILLARD M · 2019 to 2023
$2.7M
Effects of dietary restriction on age-related neurophysiological adaptations: frombehavior to single dopaminergic neuronsR01AG052606 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI BECKSTEAD, MICHAEL J · 2016 to 2020
$2.1M
Ventral tegmental area involvement in Alzheimer's pathologyR21AG072811 · NIA · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI BECKSTEAD, MICHAEL J · 2021 to 2021
$481k
Multimodal ventral tegmental area decrements in a mouse Alzheimer's modelF31AG079620 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI BLANKENSHIP, HARRIS · 2022 to 2024
$110k
Plasticity of GABA input to VTA dopamine neurons in opioid use disordersI01BX005396 · VA · OKLAHOMA CITY VA MEDICAL CENTER · PI BECKSTEAD, MICHAEL J · 2022 to 2025
–
BLRD Research Career Scientist Award ApplicationIK6BX006033 · VA · OKLAHOMA CITY VA MEDICAL CENTER · PI FREEMAN, WILLARD M · 2022 to 2025
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BLRD VA I01 BX005396BLRD VA IK6 BX006033NIA NIH HHS F31 AG079620NIA NIH HHS P30 AG050911NIA NIH HHS R01 AG052606NIA NIH HHS R01 AG059430NIA NIH HHS R21 AG072811
6 · The paper itself

Abstract

Alzheimer's disease (AD) patients exhibit neuropsychiatric symptoms that extend beyond classical cognitive deficits, suggesting involvement of subcortical areas. Here, we investigated the role of midbrain dopamine (DA) neurons in AD using the amyloid + tau-driven 3xTg-AD mouse model. We found deficits in reward-based operant learning in AD mice, suggesting possible VTA DA neuron dysregulation. Physiological assessment revealed hyperexcitability and disrupted firing in DA neurons caused by reduced activity of small-conductance calcium-activated potassium (SK) channels. RNA sequencing from contents of single patch-clamped DA neurons (Patch-seq) identified up-regulation of the SK channel modulator casein kinase 2 (CK2). Pharmacological inhibition of CK2 restored SK channel activity and normal firing patterns in 3xTg-AD mice. These findings shed light on a complex interplay between neuropsychiatric symptoms and subcortical circuits in AD, paving the way for novel treatment strategies.

Identifiers

PMID38014232
PMCPMC10680865
OpenAlexW4388750227

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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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.