Nicotine attenuates D-galactose- induced hippocampal aging-like alterations with α7-nAChR- associated mechanisms
- 1Beijing Life Science Academy , ,
- 2Key Laboratory of Tobacco Biological Effects , ,
Abstract
Background: Chronic D-galactose exposure produces selected behavioral and cellular changes associated with aging. We examined whether nicotine attenuates these changes and whether its effects differ between wild-type rats and α7 nicotinic acetylcholine receptor (α7-nAChR) knockout rats.
Methods: Female and male rats received saline, D-galactose (180 mg/kg/day), or D-galactose plus nicotine (0.5 mg/kg/day) for 49 days. We assessed spatial behavior, hippocampal staining and gene expression, and peripheral biochemical measures. Nineteen animal endpoints were analyzed using sex × genotype × treatment models, with multiplicity-adjusted contrasts and unequal-variance sensitivity analyses. Exploratory hippocampal RNA sequencing included six wild-type rats per sex and treatment.
Results: Compared with wild-type rats receiving D-galactose alone, nicotine-co-treated wild-type rats had shorter latency to first target entry, lower mean distance to the target, and more platform-site crossings in the water maze. They also had higher serum reduced glutathione (GSH) and lower hippocampal astrocytic and microglial immunoreactivity. The nicotine-associated increases in platform-site crossings and serum GSH, and the reduction in hippocampal ionized calcium-binding adapter molecule 1 (IBA1) immunoreactivity, were greater in wild-type than knockout rats. These differences were supported by both variance analyses. Nicotine co-treatment was also associated with reduced senescence-associated β-galactosidase staining and lower hippocampal App, Bace1, and Psen1 mRNA levels in wild-type rats. Serum amyloid-β1–42 did not change significantly. RNA sequencing identified treatment-associated expression patterns in wild-type hippocampi.
Conclusion: Nicotine attenuated selected D-galactose-associated behavioral and hippocampal alterations. The genotype comparisons support α7-nAChR-associated modulation of platform-site crossings, serum GSH, and hippocampal IBA1. They do not establish that changes in brain GSH or amyloid production mediate these effects, or that all nicotine responses share one receptor-dependent mechanism.
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BibTeX
@article{li2026nicotine,
title = {{Nicotine attenuates D-galactose- induced hippocampal aging-like alterations with α7-nAChR- associated mechanisms}},
author = {Xin Li and Yue Li and Yingyan Li and Wenming Wang and Shuhao Ma and Jun Li and Xuan Cheng and Chunmei Guang and Enliang Hong and Huan Chen and Hongwei Hou and Qingyuan Hu},
journal = {Frontiers in aging neuroscience},
year = {2026},
month = oct,
doi = {10.3389/fnagi.2026.1947643},
url = {https://europepmc.org/article/PMC/PMC13724548},
note = {CC BY},
}
RIS
TY - JOUR
TI - Nicotine attenuates D-galactose- induced hippocampal aging-like alterations with α7-nAChR- associated mechanisms
AU - Xin Li
AU - Yue Li
AU - Yingyan Li
AU - Wenming Wang
AU - Shuhao Ma
AU - Jun Li
AU - Xuan Cheng
AU - Chunmei Guang
AU - Enliang Hong
AU - Huan Chen
AU - Hongwei Hou
AU - Qingyuan Hu
PY - 2026
DA - 2026/10/19
JO - Frontiers in aging neuroscience
DO - 10.3389/fnagi.2026.1947643
UR - https://europepmc.org/article/PMC/PMC13724548
AB - Background: Chronic D-galactose exposure produces selected behavioral and cellular changes associated with aging. We examined whether nicotine attenuates these changes and whether its effects differ between wild-type rats and α7 nicotinic acetylcholine receptor (α7-nAChR) knockout rats. Methods: Female and male rats received saline, D-galactose (180 mg/kg/day), or D-galactose plus nicotine (0.5 mg/kg/day) for 49 days. We assessed spatial behavior, hippocampal staining and gene expression, and peripheral biochemical measures. Nineteen animal endpoints were analyzed using sex × genotype × treatment models, with multiplicity-adjusted contrasts and unequal-variance sensitivity analyses. Exploratory hippocampal RNA sequencing included six wild-type rats per sex and treatment. Results: Compared with wild-type rats receiving D-galactose alone, nicotine-co-treated wild-type rats had shorter latency to first target entry, lower mean distance to the target, and more platform-site crossings in the water maze. They also had higher serum reduced glutathione (GSH) and lower hippocampal astrocytic and microglial immunoreactivity. The nicotine-associated increases in platform-site crossings and serum GSH, and the reduction in hippocampal ionized calcium-binding adapter molecule 1 (IBA1) immunoreactivity, were greater in wild-type than knockout rats. These differences were supported by both variance analyses. Nicotine co-treatment was also associated with reduced senescence-associated β-galactosidase staining and lower hippocampal App, Bace1, and Psen1 mRNA levels in wild-type rats. Serum amyloid-β1–42 did not change significantly. RNA sequencing identified treatment-associated expression patterns in wild-type hippocampi. Conclusion: Nicotine attenuated selected D-galactose-associated behavioral and hippocampal alterations. The genotype comparisons support α7-nAChR-associated modulation of platform-site crossings, serum GSH, and hippocampal IBA1. They do not establish that changes in brain GSH or amyloid production mediate these effects, or that all nicotine responses share one receptor-dependent mechanism.
SN - 1663-4365
ER -