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Updated: May 1, 2026
Quantifying Spontaneous Ca2+ Fluxes and their Downstream Effects in Primary Mouse Midbrain Neurons
Published on: September 9, 2020
Acrylamide alters neurotransmitter induced calcium responses in murine ESC-derived and primary neurons
Julia Sisnaiske1, Vanessa Hausherr1, Anne K Krug2
1IfADo - Leibniz Research Center for Working Environment and Human Factors, Dortmund, Germany.
Abstract:
Stem cell-derived specialized cell types are of interest as an alternative cell system to identify and research neurotoxic effects and modes of action. Developmental toxicity may be studied during differentiation, while organ-specific toxicity may be assessed in fully functional cells, such as neurons. In this study we tested if fully differentiated neurons derived from murine embryonic stem cells (ESCN) could be used to investigate the effects of the well characterized neurotoxic model compound acrylamide (ACR) and if ESCN behave similar to murine primary cortical neurons (pCN) from 16 days old embryos. We characterized the differentiation process of cryopreserved ESC-derived neural precursor cells (NPC) differentiating to ESCN. During the differentiation process (days 11-20) a strong increase in calcium responses to glutamate, acetylcholine and GABA were observed. Moreover, neuron specific marker proteins, β-III-tubulin, MAP2, Tau, Rbfox3 and synaptophysin showed similar patterns to pCN. In ESCN and pCN the neuronal structure, e.g. neurites, was not affected by low concentrations of ACR [0.5-1.6mM]. However, 24h incubation periods with 0.5-1.6mM ACR led to a reduction of acetylcholine and glutamate induced calcium responses. In conclusion, we show that non-cytotoxic concentrations of ACR alter neurotransmission in ESCN as well as pCN.
Insights
Stem cell-derived neurons (ESCN) effectively model acrylamide (ACR) neurotoxicity, showing similar neurotransmission alterations as primary cortical neurons (pCN). This validates ESCN as a robust system for neurotoxicity research.
Area of Science:
- Neuroscience
- Toxicology
- Stem Cell Biology
Background:
- Stem cell-derived specialized cells offer alternative models for studying neurotoxic effects.
- Investigating neurotoxicity in differentiated neurons, such as stem cell-derived neurons (ESCN), is crucial for understanding chemical impacts.
Purpose of the Study:
- To evaluate murine embryonic stem cell-derived neurons (ESCN) as a model for acrylamide (ACR) neurotoxicity.
- To compare the response of ESCN to ACR with murine primary cortical neurons (pCN).
Main Methods:
- Characterization of ESC-derived neural precursor cells (NPC) differentiating into ESCN.
- Assessment of neuronal marker protein expression and functional calcium responses.
- Exposure of ESCN and pCN to acrylamide (ACR) and evaluation of structural and functional changes.
Main Results:
- ESCN differentiation showed increased calcium responses and expression of neuron-specific markers, similar to pCN.
- Non-cytotoxic concentrations of ACR (0.5-1.6mM) did not affect neuronal structure in ESCN or pCN.
- ACR exposure reduced acetylcholine and glutamate-induced calcium responses in both ESCN and pCN.
Conclusions:
- Murine embryonic stem cell-derived neurons (ESCN) serve as a viable model for studying neurotoxic effects.
- Acrylamide (ACR) alters neurotransmission in ESCN at non-cytotoxic concentrations, mirroring effects in primary cortical neurons (pCN).
- ESCN provide a valuable tool for neurotoxicity research and understanding chemical modes of action.
