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The Nicotine Paradox: Neuroprotection or Neurotoxicity?

Scientists unveil the mechanism behind nicotinic effects on cognition, presenting potential targets for cognitive improvement.

Nicotine is a natural chemical that can be found in tobacco that makes smoking a difficult habit to kick. The effects of nicotine on the central nervous system remains a mystery. On one hand, it disturbs the functional development of the fetal brain, and on the other, it can improve learning, memory, and attention. By regulating the release of neurotransmitters, nicotine can influence the cognitive behaviours of humans and animals. Therefore, if we can outline how neurotransmitters are metabolised, it could present an important strategy in explaining the mechanisms behind nicotinic effects on cognition.

While in vitro and in vivo studies have been carried out on the effects of nicotine on neurotransmitters, they were mainly restricted to real-time and simultaneous detection of neurotransmitters. More extensive investigations are needed to look into the dynamic effects of nicotine on hippocampal neurotransmitters.

In a study conducted by Dr. Luo Qian and colleagues at the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences, the team unveiled a possible mechanism of nicotine on hippocampal-dependent cognition.

In recent years, the integration of online cell dynamic culture and real-time liquid chromatography-mass spectrometry (LC-MS) analysis has allowed the microfluidic chip-coupled with LC-MS (MC-LC-MS) system to monitor in real-time the alterations of neurotransmitter metabolism in neuronal cells during different pharmacological or physiological processes.

Therefore, to better understand the mechanism of nicotine on cognition, the MC-LC-MS system was used. HT22 cells were first seeded into the cell chamber on the microfluidic chip and incubated under 5 per cent CO2 air and 37 degrees Celsius. The morphology of the cells was obtained, and the extracellular neurotransmitters and their metabolites were analysed in real-time with LC-MS.

“We found that HT22 cells mainly released related neurotransmitters of tryptophan and choline metabolism,” said Dr. Luo.

The HT22 cells were then dynamic cultured and exposed to nicotine at different concentrations under a specific flow rate, and acute and chronic exposures were measured after eight and 48 hours respectively. The results revealed that nicotine exposure at different levels significantly modified the metabolism and secretion of neurotransmitters of HT22 cells, and their alterations were closely related to the exposure doses and duration.

The results obtained suggest that acute exposure to nicotine was advantageous to protect neurons, especially cognitive enhancements, and the increased picolinic acid continued to protect neuronal cognitive function after nicotine withdrawal. In future, the team would have to further verify these results in animal models.

For now, it might be worthwhile to consider the use of nicotine for preventive action from cognitive deficits and memory impairment in neurodegenerative disorders. However, it should be noted that nicotine also has systemic adverse effects, such as high addiction, organ damage, and carcinogenicity. Furthermore, the intake of nicotine via smoking should be considered carefully as smoking is a well-known risk factor for psychiatric disorders and other diseases. [APBN]

Source: Chen et al. (2021). Real-time effects of nicotine exposure and withdrawal on neurotransmitter metabolism of hippocampal neuronal cells by microfluidic chip-coupled LC-MS. Chinese Chemical Letters.