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bioRxiv · 10.1101/2024.09.10.612190

Effect of Alcohol and Cocaine Abuse on Neuronal and Non-Neuronal Cell Turnover in the Adult Human Hippocampus

Alkass, K.·Steiner, E.·Bernard, S.·Le Maitre, T. W.·Dhanabalan, G.·Landen, M.·Spalding, K.·Frisen, J.·Mash, D. C.·Druid, H.
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Abstract

Clinical studies on humans with a history of chronic abuse of alcohol or cocaine show cognitive impairments associated with hippocampal atrophy. Adult hippocampal neurogenesis is a process important for memory formation and has been shown to be impaired by alcohol and cocaine in rodent models. It has thus been suggested that a reduction in adult neurogenesis may contribute to cognitive dysfunctions seen in patients with abuse. In addition, reduced adult neurogenesis has been suggested to play a role in the pathology of addiction vulnerability. We have previously demonstrated persistent adult hippocampal neurogenesis throughout life by measuring 14C concentrations in genomic DNA, incorporated during cell division, in a mixed cohort of subjects. In this study, we use the same strategy to assess the extent of cell turnover of neuronal and non-neuronal cells in the hippocampus of humans with known history of alcohol and cocaine abuse and compare these with healthy controls. We find that there is significant neuronal and non-neuronal turnover in healthy controls, as well as in individuals with long term alcohol use orcocaine use. Using mathematical modelling, we compare the extent of cell turnover of neurons and non-neuronal cells and did not find any significant difference between healthy controls and the two addiction groups. While we cannot exclude scenarios of altered adult neurogenesis over shorter periods of time, our data does not support the theory of low neurogenesis as a mechanism of addiction vulnerability.

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Alkass, K., Steiner, E., Bernard, S., Le Maitre, T. W., Dhanabalan, G., Landen, M., Spalding, K., Frisen, J., Mash, D. C., Druid, H.. 2024-09-14. Effect of Alcohol and Cocaine Abuse on Neuronal and Non-Neuronal Cell Turnover in the Adult Human Hippocampus. https://doi.org/10.1101/2024.09.10.612190

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