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Updated: Sep 26, 2026
Live Imaging of Nicotine Induced Calcium Signaling and Neurotransmitter Release Along Ventral Hippocampal Axons
Published on: June 24, 2015
Spatially Resolved Multi-Omics Reveals Brain-Kidney Compartmentalization and Region-Specific Molecular Reprogramming
Qian Li1,2,3, Lutao Xu1,2, Mingyu Zhu1
1Beijing Life Science Academy, Beijing 102299, China.
Background:
Traditional bulk tissue analyses obscure the precise spatial compartmentalization of nicotine and its molecular effects within individual anatomical regions. This study aimed to develop and apply a high-resolution spatial multi-omics framework to characterize the localized disposition and functional responses induced by an acute nicotine challenge.
Methods:
We established a spatial multi-omics framework integrating matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-TOF MSI), air-flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI), laser microdissection (LMD)-based microscale data-independent acquisition (microDIA) proteomics, and targeted LC-MS/MS. This platform was used to analyze the kidney and five brain regions in rats subjected to an acute nicotine challenge following an adaptation regimen.
Results:
Spatial mapping revealed distinct peripheral and central distribution patterns: nicotine, cotinine, and nornicotine accumulated predominantly in the renal cortex and medulla, whereas their distribution in the brain is region-dependent, with a prominent 3-hydroxycotinine signal in the olfactory bulb. Avoiding tissue homogenization enabled these spatial distributions to be linked to localized functional responses. The striatal dopamine/DOPAC axis showed the strongest acute neurochemical response, consistent with increased dopamine turnover. Spatial metabolomics further demonstrated robust, region-specific metabolic reprogramming, with the hippocampus showing the greatest metabolic variance. LMD-resolved proteomics identified protein-level changes, particularly in the olfactory bulb and thalamus. Cross-omics revealed coordinated alterations in purine, pyrimidine, glycerophospholipid, and alanine/aspartate/glutamate metabolism, with the thalamus showing the greatest extensive metabolite-protein concordance.
Conclusions:
These findings characterize acute nicotine exposure as a spatially compartmentalized process involving renal handling, region-specific brain distribution, and localized molecular response programs.
