1. Academic Validation
  2. Demyelination in the medial prefrontal cortex by withdrawal from chronic nicotine causes impaired cognitive memory

Demyelination in the medial prefrontal cortex by withdrawal from chronic nicotine causes impaired cognitive memory

  • Prog Neuropsychopharmacol Biol Psychiatry. 2023 Nov 28:110901. doi: 10.1016/j.pnpbp.2023.110901.
Bing Huang 1 Zifei Chen 2 Fang Huang 3 Fenfei Gao 4 Jieling Chen 5 Peipei Liu 6 Zhijie Lu 5 Weiyuan Chen 2 Jie Wu 7
Affiliations

Affiliations

  • 1 Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Guangdong, China; Brain Function and Disease Laboratory, Shantou University Medical College, Guangdong, China; Department of Pharmacology, Shantou University Medical College, 22 Xinling Road, Shantou 515041, Guangdong Province, China. Electronic address: bhuangfd@stu.edu.cn.
  • 2 Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Guangdong, China.
  • 3 Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou, Guangdong, China.
  • 4 Department of Pharmacology, Shantou University Medical College, 22 Xinling Road, Shantou 515041, Guangdong Province, China.
  • 5 Brain Function and Disease Laboratory, Shantou University Medical College, Guangdong, China.
  • 6 Clinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
  • 7 Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Guangdong, China; Brain Function and Disease Laboratory, Shantou University Medical College, Guangdong, China.
Abstract

Epidemiological studies revealed deficits in cognitive learning and memory in smokers who withdrawal from smoking, but the molecular mechanisms underlying it is unclear. Here, we employed the novel object recognition task (NORT) to evaluate cognitive memory and found impaired memory and motor skills after withdrawal from chronic nicotine. Myelin sheath hastens the conduction of signals along axons and thus plays a critical role in learning and memory. We found no effect of nicotine withdrawal on the myelination in both of the Ventral tegmental area (VTA) and Nucleus accumbens (NAc) regions, but unexpectedly, we observed a demyelination phenomenon in the medial prefrontal cortex (mPFC) after withdrawal from chronic nicotine. Moreover, we found a positive correlation between the impaired memory and demyelination, and pharmaceutical rescue of myelination by clemastine specifically improved the impaired recognition memory but not the decreased motor skills caused by withdrawal from chronic nicotine. We further found nicotine directly acts on oligodendrocytes with OPCs potential to decrease their myelination process. Taken together, these results demonstrate demyelination in the mPFC causes impaired recognition memory and reveal a potential of enhancing myelination as a therapeutic strategy to alleviate cognitive memory deficits caused by smoking withdrawal.

Keywords

Cognitive memory; Demyelination; Medial prefrontal cortex (mPFC); Withdrawal from chronic nicotine.

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