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Research Article | Open Access

Arecoline causes cognitive impairment and potential addiction via disturbing Kenyon cells in bumblebee brain

Huiling Liua, Xiaohuan Mua, Rongrong Fana, Jieteng Chena, Jie Mab, Liang Mengb, Xiaosong Hua, Hao Zhenga, Shanshan Liub, Xiaofei Wanga
National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture and Rural Affairs, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
BGI-Qingdao, Qingdao 266555, China

Peer review under responsibility of Beijing Academy of Food Sciences.

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Highlights

• Arecoline induces locomotor hyperactivity and cognitive impairment.

• Arecoline specifically targets Kenyon cells in the brain.

• Low-dose arecoline affects the expression of genes related to addiction.

• High-dose arecoline induces Calcium dyshomeostasis in lKC subcluster.

Graphical Abstract

Abstract

Areca nut is the basic ingredient of betel quid, which is chewed by hundreds of millions of people in South-Eastern Asia. Chewing of areca nut has been associated with oral cancers potentially due to its specific alkaloids, among which arecoline constitutes about 90% of total fraction. Being the world’s fourth most commonly used psychoactive substance, arecoline evokes stimulation, addiction, and other direct neurological effects, while its misuse correlates to neurotoxic effects. However, what might underlie its neurotoxic mechanisms has been poorly documented. The brain is encoded by a complex network of neuronal and glial cell types, and neurotoxicity of hazardous compounds present transcriptional heterogeneity. Recently, the eusocial bumblebee has been used as a model for studying brain effects, with sophisticated cognitive capability and precisely measured brain architecture. Here, we decipher cell-type-specific mental risks to arecoline using bumblebees. Arecoline induced locomotor hyperactivity and cognitive impairment. Single nucleus RNA sequencing (snRNA-seq) unearthed arecoline-induced cell-specific responses, primarily targeted on Kenyon cells (KC). Moreover, high-dose arecoline induced distinctive cell responses among KC subtypes, particularly class Ⅰ large Kenyon cell (lKC), leading to DNA damage, excitatory/inhibitory (E/I) imbalance, and calcium dyshomeostasis, which potentially resulted in cognitive impairment. Given arecoline’s popularity and growing exposure risks to humans, neurological health risks of areca nut warrant serious consideration.

Keywords

ArecolineBombus terrestrisCognitive abilitySingle-nucleus RNA sequencingKenyon cell

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Food Science and Human Wellness
Volume 14 Issue 7,
July 2025
Article number: 9250167
DOI: 10.26599/FSHW.2024.9250167
Cite this article:
Liu H, Mu X, Fan R, et al. Arecoline causes cognitive impairment and potential addiction via disturbing Kenyon cells in bumblebee brain. Food Science and Human Wellness, 2025, 14(7): 9250167. https://doi.org/10.26599/FSHW.2024.9250167

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Received: 08 November 2023
Revised: 18 December 2023
Accepted: 31 January 2024
Published: 11 June 2025
© 2025 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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