High-dose caffeine reduces neurite branching and alters expression of selected genes in immature primary rat cortical and hippocampal cell cultures.
- 1Neuropharmacology and Biological Addiction Research, Department of Pharmaceutical Biosciences, Uppsala University, Sweden.
Abstract
The consumption of energy drinks with high concentrations of caffeine is increasing among adolescents and young adults. Caffeine is a central nervous system stimulant that acts as a non-selective antagonist of adenosine receptors. Adenosine receptor signalling is involved in several processes in the brain, but the role it plays in caffeine-induced effects on developing neuronal cells is poorly understood. This study investigates how caffeine, the selective adenosine A2a receptor antagonist istradefylline and the adenosine A2a receptor agonist CGS21680 affect cell viability, neurite outgrowth, branching and mRNA expression in immature primary rat cortical and hippocampal cell cultures. Caffeine significantly decreased the number of branches, junctions and endpoints in both hippocampal and cortical cells, with the effect appearing to be more potent in hippocampal cells. In addition, high concentrations of caffeine decreased neurite length and mitochondrial function in both hippocampal and cortical cells, as well as decreasing MAO-B and tryptophan hydroxylase 2 expression in cortical cells. Istradefylline also decreased neurite branching and outgrowth in hippocampal cells, although these effects were less pronounced than those observed with caffeine. These findings indicate that caffeine reduces neuronal branching and that high caffeine concentrations also reduce neurite length and mitochondrial activity and affect genes involved in monoaminergic signalling and neuronal function in developing neuronal cells. These findings may be relevant to understanding the cellular consequences of high caffeine exposure during brain development.
Related
- High Intratumoral PROS1 Expression Is Associated with Improved Survival, Reduced Hypoxia Score Markers, and Alterations in Gene Expression Associated with Oncogene Signaling and Cell Cycle Signaling in Selected Solid Tumors
- Diosmin Attenuates PTSD-like Behaviors and Hippocampal Astrocyte Alterations with Reduced STAT1 and CXCL9 Expression in an SPS&S Mouse Model
- Long-term dysregulation of histone acetylation, BDNF expression, and the hippocampal transcriptome in adult rats exhibiting a depressive-like phenotype following repeated chlorpyrifos exposure
- MCH-02, a synthetic macamide analog with in vitro FAAH-inhibitory activity, modulates hippocampal endocannabinoid system and BK channel expression without preventing PTZ-induced progressive seizure susceptibility in rats
- Customized BioRoot Inlay for the Management of an Immature Tooth With a Blunderbuss Canal: A Novel Biomimetic Approach
BibTeX
@article{bjurling2026highdose,
title = {{High-dose caffeine reduces neurite branching and alters expression of selected genes in immature primary rat cortical and hippocampal cell cultures.}},
author = {Sara Florén Lind Bjurling and Frida Stam and Erik Nylander and Alfhild Grönbladh},
journal = {IBRO neuroscience reports},
year = {2026},
month = oct,
doi = {10.1016/j.ibneur.2026.10.002},
url = {https://europepmc.org/article/MED/42997023},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - High-dose caffeine reduces neurite branching and alters expression of selected genes in immature primary rat cortical and hippocampal cell cultures.
AU - Sara Florén Lind Bjurling
AU - Frida Stam
AU - Erik Nylander
AU - Alfhild Grönbladh
PY - 2026
DA - 2026/10/10
JO - IBRO neuroscience reports
DO - 10.1016/j.ibneur.2026.10.002
UR - https://europepmc.org/article/MED/42997023
AB - The consumption of energy drinks with high concentrations of caffeine is increasing among adolescents and young adults. Caffeine is a central nervous system stimulant that acts as a non-selective antagonist of adenosine receptors. Adenosine receptor signalling is involved in several processes in the brain, but the role it plays in caffeine-induced effects on developing neuronal cells is poorly understood. This study investigates how caffeine, the selective adenosine A2a receptor antagonist istradefylline and the adenosine A2a receptor agonist CGS21680 affect cell viability, neurite outgrowth, branching and mRNA expression in immature primary rat cortical and hippocampal cell cultures. Caffeine significantly decreased the number of branches, junctions and endpoints in both hippocampal and cortical cells, with the effect appearing to be more potent in hippocampal cells. In addition, high concentrations of caffeine decreased neurite length and mitochondrial function in both hippocampal and cortical cells, as well as decreasing MAO-B and tryptophan hydroxylase 2 expression in cortical cells. Istradefylline also decreased neurite branching and outgrowth in hippocampal cells, although these effects were less pronounced than those observed with caffeine. These findings indicate that caffeine reduces neuronal branching and that high caffeine concentrations also reduce neurite length and mitochondrial activity and affect genes involved in monoaminergic signalling and neuronal function in developing neuronal cells. These findings may be relevant to understanding the cellular consequences of high caffeine exposure during brain development.
SN - 2667-2421
ER -