Caffeine compromises proliferation of human hippocampal progenitor cells

Vikki Houghton; Andrea Du Preez; Sophie Lefevre-Arbogast; Chiara De Lucia; Dorrain  Low; Mireia Urpi-Sarda; Silvie R.  Ruigrok; Barbara  Altendorfer; Raúl  González-Domínguez; Cristina Andres-Lacueva; Ludwig Aigner; Paul J. Lucassen; Aniko Korosi; Cécilia Samieri; Claudine Manach; Sandrine Thuret

doi:10.3389/fcell.2020.00806

Caffeine compromises proliferation of human hippocampal progenitor cells

Vikki Houghton, Andrea Du Preez, Sophie Lefevre-Arbogast, Chiara De Lucia, Dorrain Low, Mireia Urpi-Sarda, Silvie R. Ruigrok, Barbara Altendorfer, Raúl González-Domínguez, Cristina Andres-Lacueva, Ludwig Aigner, Paul J. Lucassen, Aniko Korosi, Cécilia Samieri, Claudine Manach, Sandrine Thuret

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

104 Downloads (Pure)

Abstract

The age-associated reduction in the proliferation of neural stem cells (NSCs) has been associated with cognitive decline. Numerous factors have been shown to modulate this process, including dietary components. Frequent consumption of caffeine has been correlated with an increased risk of cognitive decline, but further evidence of a negative effect on hippocampal progenitor proliferation is limited to animal models. Here, we used a human hippocampal progenitor cell line to investigate the effects of caffeine on hippocampal progenitor integrity and proliferation specifically. The effects of five caffeine concentrations (0 mM = control, 0.1 mM ∼ 150 mg, 0.25 mM ∼ 400 mg, 0.5 mM ∼ 750 mg, and 1.0 mM ∼ 1500 mg) were measured following acute (1 day) and repeated (3 days) exposure. Immunocytochemistry was used to quantify hippocampal progenitor integrity (i.e., SOX2- and Nestin-positive cells), proliferation (i.e., Ki67-positive cells), cell count (i.e., DAPI-positive cells), and apoptosis (i.e., CC3-positive cells). We found that progenitor integrity was significantly reduced in supraphysiological caffeine conditions (i.e., 1.0 mM ∼ 1500 mg), but relative to the lowest caffeine condition (i.e., 0.1 mM ∼ 150 mg) only. Moreover, repeated exposure to supraphysiological caffeine concentrations (i.e., 1.0 mM ∼ 1500 mg) was found to affect proliferation, significantly reducing % Ki67-positive cells relative to control and lower caffeine dose conditions (i.e., 0.1 mM ∼ 150 mg and 0.25 mM ∼ 400 mg). Caffeine treatment did not influence apoptosis and there were no significant differences in any measure between lower doses of caffeine (i.e., 0.1 mM, 0.25 mM, 0.5 mM) – representative of daily human caffeine intake – and control conditions. Our study demonstrates that dietary components such as caffeine can influence NSC integrity and proliferation and may be indicative of a mechanism by which diet affects cognitive outcomes.

Original language	English
Article number	806
Journal	Frontiers in Cell and Developmental Biology
Volume	8
DOIs	https://doi.org/10.3389/fcell.2020.00806
Publication status	Published - 8 Sept 2020

Keywords

adult hippocampal neurogenesis
caffeine
diet
hippocampal progenitor integrity
hippocampal progenitor proliferation

Access to Document

10.3389/fcell.2020.00806Licence: CC BY

Caffeine compromises proliferation of_HOUGHTON_Acc31Jul2020_GOLD AAMAccepted author manuscript, 4.66 MBLicence: CC BY

https://www.frontiersin.org/articles/10.3389/fcell.2020.00806/abstractLicence: CC BY

Cite this

Houghton, V., Du Preez, A., Lefevre-Arbogast, S., De Lucia, C., Low, D., Urpi-Sarda, M., Ruigrok, S. R., Altendorfer, B., González-Domínguez, R., Andres-Lacueva, C., Aigner, L., Lucassen, P. J., Korosi, A., Samieri, C., Manach, C., & Thuret, S. (2020). Caffeine compromises proliferation of human hippocampal progenitor cells. Frontiers in Cell and Developmental Biology, 8, Article 806. https://doi.org/10.3389/fcell.2020.00806

@article{80b7ed2c9cca413481b2ecd2b8844bb7,

title = "Caffeine compromises proliferation of human hippocampal progenitor cells",

abstract = "The age-associated reduction in the proliferation of neural stem cells (NSCs) has been associated with cognitive decline. Numerous factors have been shown to modulate this process, including dietary components. Frequent consumption of caffeine has been correlated with an increased risk of cognitive decline, but further evidence of a negative effect on hippocampal progenitor proliferation is limited to animal models. Here, we used a human hippocampal progenitor cell line to investigate the effects of caffeine on hippocampal progenitor integrity and proliferation specifically. The effects of five caffeine concentrations (0 mM = control, 0.1 mM ∼ 150 mg, 0.25 mM ∼ 400 mg, 0.5 mM ∼ 750 mg, and 1.0 mM ∼ 1500 mg) were measured following acute (1 day) and repeated (3 days) exposure. Immunocytochemistry was used to quantify hippocampal progenitor integrity (i.e., SOX2- and Nestin-positive cells), proliferation (i.e., Ki67-positive cells), cell count (i.e., DAPI-positive cells), and apoptosis (i.e., CC3-positive cells). We found that progenitor integrity was significantly reduced in supraphysiological caffeine conditions (i.e., 1.0 mM ∼ 1500 mg), but relative to the lowest caffeine condition (i.e., 0.1 mM ∼ 150 mg) only. Moreover, repeated exposure to supraphysiological caffeine concentrations (i.e., 1.0 mM ∼ 1500 mg) was found to affect proliferation, significantly reducing % Ki67-positive cells relative to control and lower caffeine dose conditions (i.e., 0.1 mM ∼ 150 mg and 0.25 mM ∼ 400 mg). Caffeine treatment did not influence apoptosis and there were no significant differences in any measure between lower doses of caffeine (i.e., 0.1 mM, 0.25 mM, 0.5 mM) – representative of daily human caffeine intake – and control conditions. Our study demonstrates that dietary components such as caffeine can influence NSC integrity and proliferation and may be indicative of a mechanism by which diet affects cognitive outcomes.",

keywords = "adult hippocampal neurogenesis, caffeine, diet, hippocampal progenitor integrity, hippocampal progenitor proliferation",

author = "Vikki Houghton and {Du Preez}, Andrea and Sophie Lefevre-Arbogast and {De Lucia}, Chiara and Dorrain Low and Mireia Urpi-Sarda and Ruigrok, {Silvie R.} and Barbara Altendorfer and Ra{\'u}l Gonz{\'a}lez-Dom{\'i}nguez and Cristina Andres-Lacueva and Ludwig Aigner and Lucassen, {Paul J.} and Aniko Korosi and C{\'e}cilia Samieri and Claudine Manach and Sandrine Thuret",

year = "2020",

month = sep,

day = "8",

doi = "10.3389/fcell.2020.00806",

language = "English",

volume = "8",

journal = "Frontiers in Cell and Developmental Biology",

issn = "2296-634X",

publisher = "Frontiers Media S.A.",

}

Houghton, V , Du Preez, A, Lefevre-Arbogast, S, De Lucia, C, Low, D, Urpi-Sarda, M, Ruigrok, SR, Altendorfer, B, González-Domínguez, R, Andres-Lacueva, C, Aigner, L, Lucassen, PJ, Korosi, A, Samieri, C, Manach, C & Thuret, S 2020, 'Caffeine compromises proliferation of human hippocampal progenitor cells', Frontiers in Cell and Developmental Biology, vol. 8, 806. https://doi.org/10.3389/fcell.2020.00806

TY - JOUR

T1 - Caffeine compromises proliferation of human hippocampal progenitor cells

AU - Houghton, Vikki

AU - Du Preez, Andrea

AU - Lefevre-Arbogast, Sophie

AU - De Lucia, Chiara

AU - Low, Dorrain

AU - Urpi-Sarda, Mireia

AU - Ruigrok, Silvie R.

AU - Altendorfer, Barbara

AU - González-Domínguez, Raúl

AU - Andres-Lacueva, Cristina

AU - Aigner, Ludwig

AU - Lucassen, Paul J.

AU - Korosi, Aniko

AU - Samieri, Cécilia

AU - Manach, Claudine

AU - Thuret, Sandrine

PY - 2020/9/8

Y1 - 2020/9/8

N2 - The age-associated reduction in the proliferation of neural stem cells (NSCs) has been associated with cognitive decline. Numerous factors have been shown to modulate this process, including dietary components. Frequent consumption of caffeine has been correlated with an increased risk of cognitive decline, but further evidence of a negative effect on hippocampal progenitor proliferation is limited to animal models. Here, we used a human hippocampal progenitor cell line to investigate the effects of caffeine on hippocampal progenitor integrity and proliferation specifically. The effects of five caffeine concentrations (0 mM = control, 0.1 mM ∼ 150 mg, 0.25 mM ∼ 400 mg, 0.5 mM ∼ 750 mg, and 1.0 mM ∼ 1500 mg) were measured following acute (1 day) and repeated (3 days) exposure. Immunocytochemistry was used to quantify hippocampal progenitor integrity (i.e., SOX2- and Nestin-positive cells), proliferation (i.e., Ki67-positive cells), cell count (i.e., DAPI-positive cells), and apoptosis (i.e., CC3-positive cells). We found that progenitor integrity was significantly reduced in supraphysiological caffeine conditions (i.e., 1.0 mM ∼ 1500 mg), but relative to the lowest caffeine condition (i.e., 0.1 mM ∼ 150 mg) only. Moreover, repeated exposure to supraphysiological caffeine concentrations (i.e., 1.0 mM ∼ 1500 mg) was found to affect proliferation, significantly reducing % Ki67-positive cells relative to control and lower caffeine dose conditions (i.e., 0.1 mM ∼ 150 mg and 0.25 mM ∼ 400 mg). Caffeine treatment did not influence apoptosis and there were no significant differences in any measure between lower doses of caffeine (i.e., 0.1 mM, 0.25 mM, 0.5 mM) – representative of daily human caffeine intake – and control conditions. Our study demonstrates that dietary components such as caffeine can influence NSC integrity and proliferation and may be indicative of a mechanism by which diet affects cognitive outcomes.

AB - The age-associated reduction in the proliferation of neural stem cells (NSCs) has been associated with cognitive decline. Numerous factors have been shown to modulate this process, including dietary components. Frequent consumption of caffeine has been correlated with an increased risk of cognitive decline, but further evidence of a negative effect on hippocampal progenitor proliferation is limited to animal models. Here, we used a human hippocampal progenitor cell line to investigate the effects of caffeine on hippocampal progenitor integrity and proliferation specifically. The effects of five caffeine concentrations (0 mM = control, 0.1 mM ∼ 150 mg, 0.25 mM ∼ 400 mg, 0.5 mM ∼ 750 mg, and 1.0 mM ∼ 1500 mg) were measured following acute (1 day) and repeated (3 days) exposure. Immunocytochemistry was used to quantify hippocampal progenitor integrity (i.e., SOX2- and Nestin-positive cells), proliferation (i.e., Ki67-positive cells), cell count (i.e., DAPI-positive cells), and apoptosis (i.e., CC3-positive cells). We found that progenitor integrity was significantly reduced in supraphysiological caffeine conditions (i.e., 1.0 mM ∼ 1500 mg), but relative to the lowest caffeine condition (i.e., 0.1 mM ∼ 150 mg) only. Moreover, repeated exposure to supraphysiological caffeine concentrations (i.e., 1.0 mM ∼ 1500 mg) was found to affect proliferation, significantly reducing % Ki67-positive cells relative to control and lower caffeine dose conditions (i.e., 0.1 mM ∼ 150 mg and 0.25 mM ∼ 400 mg). Caffeine treatment did not influence apoptosis and there were no significant differences in any measure between lower doses of caffeine (i.e., 0.1 mM, 0.25 mM, 0.5 mM) – representative of daily human caffeine intake – and control conditions. Our study demonstrates that dietary components such as caffeine can influence NSC integrity and proliferation and may be indicative of a mechanism by which diet affects cognitive outcomes.

KW - adult hippocampal neurogenesis

KW - caffeine

KW - diet

KW - hippocampal progenitor integrity

KW - hippocampal progenitor proliferation

UR - http://www.scopus.com/inward/record.url?scp=85091428877&partnerID=8YFLogxK

U2 - 10.3389/fcell.2020.00806

DO - 10.3389/fcell.2020.00806

M3 - Article

SN - 2296-634X

VL - 8

JO - Frontiers in Cell and Developmental Biology

JF - Frontiers in Cell and Developmental Biology

M1 - 806

ER -

Caffeine compromises proliferation of human hippocampal progenitor cells

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this