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Peer-reviewedCC BYNeuropharmacology

Chronic alcohol exposure produces pathology-dependent corticostriatal circuit remodeling in Aβ- and tau-based mouse models of Alzheimer's disease

  • Yufei S. Huang1
  • Xueyi Xie2
  • Zhenbo Huang2
  • Himanshu Gangal2
  • Ruifeng Chen2
  • Xuehua Wang2
  • Jianrong Li3
  • Jun Wang4
4 affiliations
  1. 1Department of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX, 77807, USA; Institute for Neuroscience, Texas A&M University, College Station, TX, 77843, USA
  2. 2Department of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX, 77807, USA
  3. 3Institute for Neuroscience, Texas A&M University, College Station, TX, 77843, USA; Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA
  4. 4Department of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX, 77807, USA; Institute for Neuroscience, Texas A&M University, College Station, TX, 77843, USA. Electronic address: [email protected]
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Abstract

Chronic alcohol consumption is a major risk factor for Alzheimer's disease (AD), yet how alcohol exposure alters neural circuits under distinct pathological conditions remains poorly understood. Here, we used a humanized Aβ knock-in model (hAPP-KI) and a tauopathy model (PS19) to test how the same alcohol exposure affects distinct pathological contexts. In hAPP-KI mice, alcohol exposure increased cortical Aβ burden, enhanced excitatory synaptic transmission in the medial prefrontal cortex (mPFC), and reduced glutamatergic transmission from the mPFC to the dorsomedial striatum (DMS). In contrast, in PS19 mice, alcohol exposure increased tau phosphorylation and elevated mPFC-to-DMS glutamatergic transmission without altering local cortical excitatory input. Alcohol exposure was also associated with distinct microglial responses across pathological contexts. To assess microglial contributions to cortical excitatory regulation, we depleted microglia in wild-type mice and observed enhanced cortical glutamatergic transmission. Together, these findings suggest pathology-dependent circuit remodeling and microglial responses associated with alcohol exposure in AD models.

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Cite

BibTeXRIS
BibTeX
@article{huang2026chronic,
  title = {{Chronic alcohol exposure produces pathology-dependent corticostriatal circuit remodeling in Aβ- and tau-based mouse models of Alzheimer's disease}},
  author = {Yufei S. Huang and Xueyi Xie and Zhenbo Huang and Himanshu Gangal and Ruifeng Chen and Xuehua Wang and Jianrong Li and Jun Wang},
  journal = {Neuropharmacology},
  year = {2026},
  month = jun,
  doi = {10.1016/j.neuropharm.2026.111069},
  url = {https://doi.org/10.1016/j.neuropharm.2026.111069},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Chronic alcohol exposure produces pathology-dependent corticostriatal circuit remodeling in Aβ- and tau-based mouse models of Alzheimer's disease
AU  - Yufei S. Huang
AU  - Xueyi Xie
AU  - Zhenbo Huang
AU  - Himanshu Gangal
AU  - Ruifeng Chen
AU  - Xuehua Wang
AU  - Jianrong Li
AU  - Jun Wang
PY  - 2026
DA  - 2026/06/06
JO  - Neuropharmacology
DO  - 10.1016/j.neuropharm.2026.111069
UR  - https://doi.org/10.1016/j.neuropharm.2026.111069
AB  - Chronic alcohol consumption is a major risk factor for Alzheimer's disease (AD), yet how alcohol exposure alters neural circuits under distinct pathological conditions remains poorly understood. Here, we used a humanized Aβ knock-in model (hAPP-KI) and a tauopathy model (PS19) to test how the same alcohol exposure affects distinct pathological contexts. In hAPP-KI mice, alcohol exposure increased cortical Aβ burden, enhanced excitatory synaptic transmission in the medial prefrontal cortex (mPFC), and reduced glutamatergic transmission from the mPFC to the dorsomedial striatum (DMS). In contrast, in PS19 mice, alcohol exposure increased tau phosphorylation and elevated mPFC-to-DMS glutamatergic transmission without altering local cortical excitatory input. Alcohol exposure was also associated with distinct microglial responses across pathological contexts. To assess microglial contributions to cortical excitatory regulation, we depleted microglia in wild-type mice and observed enhanced cortical glutamatergic transmission. Together, these findings suggest pathology-dependent circuit remodeling and microglial responses associated with alcohol exposure in AD models.
SN  - 0028-3908
SN  - 1873-7064
ER  -