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Role of brain serotonin in age-related decline in physical activity in mice

Published online by Cambridge University Press:  08 February 2022

P.B. Martinez de Morentin ,
M. Arcon ,
A. Leeson-Payne ,
Y. Martynova  and
L.K. Heisler
P.B. Martinez de Morentin
Affiliation:
The Rowett Institute, University of Aberdeen, Aberdeen, UK
M. Arcon
Affiliation:
The Rowett Institute, University of Aberdeen, Aberdeen, UK
A. Leeson-Payne
Affiliation:
The Rowett Institute, University of Aberdeen, Aberdeen, UK
Y. Martynova
Affiliation:
The Rowett Institute, University of Aberdeen, Aberdeen, UK
L.K. Heisler
Affiliation:
The Rowett Institute, University of Aberdeen, Aberdeen, UK
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Abstract

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Proceedings of the Nutrition Society , Volume 81 , Issue OCE1: Winter Conference 2021, 7–8 December 2021, Obesity and the brain , 2022 , E56
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Copyright © The Authors 2022

Ageing is negatively correlated with physical activity (PA) and this has an undesirable impact on overall health(Reference Gulsvik1). The neurotransmitter serotonin (5-HT) is known to be inversely correlated with physical activity(Reference Fonseca, Murakami and Mainen2). Here we investigate a serotonergic neuronal circuit involved in voluntary physical activity during ageing in mice.

We injected designed DREADD proteins (Designer Receptors Exclusively Activated by Designer Drugs) that enable non-invasive control of neuronal signalling through the Gq (hMD3q, excitatory) and Gi (hMD4i) G-protein coupled signalling pathways in the dorsal raphe nucleus (DRN) of Tph2iCre mice (tph2, rate-limiting enzyme in 5HT synthesis) to modulate 5-HT release, or in the ventral segmental area (VTA) of 5-HT2CRCre mice (5-HT type 2c receptor) to modulate activity in a 5-HT target region. Upon administration of CNO (clozapine-N-Oxide, Designer drug for DREADD) (1mg/kg, IP) and lorcaserin (3mg/kg, IP) we characterised the locomotor activity profile of all mice using TSE Phenomaster.

Our results showed that activation of Tph2DRN cells reduced PA (p < 0.05; Veh, n = 11, 12811 ± 1554 vs CNO, n = 10 8196 ± 2821, t = 2.507,df = 19,) while its inhibition induced locomotion (p < 0.001; Veh, n = 5, 13209 ± 1181, vs CNO, n = 5, 26948 ± 2515, t = 4.944, df = 8. Chemogenetic activation of 5-HT2CRVTA reduced PA (p < 0.05, Veh, n = 6, 6650 ± 1329 vs CNO, n = 9, 3587 ± 401, t = 2.606, df = 13) while its inhibition reverted the effects of lorcaserin (p < 0.01, Lorc + veh n = 6, 10704 ± 1235 vs Lorc + CNO n = 9, 16280 ± 1405, t = 2.930, df = 11)

In summary, our data indicate that the serotonin system through the 5-HT2cR signalling in the VTA is involved in the control of locomotion and identify a means to reverse age-related decline in physical activity.

Acknowledgments

This work was supported by the BBSRC (BB/R01857X/1 and BB/N017838/1) and The Royal Society of Edinburgh (RSE1122).

References

Gulsvik, AK et al. (2012) Int J Epidemol 41(2), 521–530.CrossRefGoogle Scholar
Fonseca, MS, Murakami, M & Mainen, ZF (2015) Curr Biol 25, 306–315.10.1016/j.cub.2014.12.002CrossRefGoogle Scholar