Format

Send to

Choose Destination
Neurotoxicology. 2017 Jan;58:11-22. doi: 10.1016/j.neuro.2016.10.015. Epub 2016 Oct 29.

Influence of tetramethylenedisulfotetramine on synchronous calcium oscillations at distinct developmental stages of hippocampal neuronal cultures.

Author information

1
State Key Laboratory of Natural Medicines & Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Development, China Pharmaceutical University, Nanjing, 211198, PR China; Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, 95616, United States. Electronic address: zycao1999@hotmail.com.
2
State Key Laboratory of Natural Medicines & Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Development, China Pharmaceutical University, Nanjing, 211198, PR China.
3
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, 95616, United States.
4
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, 95616, United States. Electronic address: inpessah@ucdavis.edu.

Abstract

The spatial and temporal patterns of spontaneous synchronous Ca2+ oscillations (SCOs) regulate physiological pathways that influence neuronal development, excitability, and health. Hippocampal neuronal cultures (HN) and neuron/glia co-cultures (HNG) produced from neonatal mice were loaded with Fluo-4/AM and SCOs recorded in real-time using a Fluorescence Imaging Plate Reader at different developmental stages in vitro. HNG showed an earlier onset of SCOs, with low amplitude and low frequency SCOs at 4days in vitro (DIV), whereas HN were quiescent at this point. SCO amplitude peaked at 9 DIV for both cultures. SCO network frequency peaked at 12 DIV in HN, whereas in HNG the frequency peaked at 6 DIV. SCO patterns were associated with the temporal development of neuronal networks and their ratio of glutamatergic to GABAergic markers of excitatory/inhibitory balance. HN and HNG exhibited differential responses to the convulsant tetramethylenedisulfotetramine (TETS) and were highly dependent on DIV. In HN, TETS triggered an acute rise of intracellular Ca2+ (Phase I response) only in 14 DIV and a sustained decrease of SCO frequency with increased amplitude (Phase II response) at all developmental stages. In HNG, TETS decreased the SCO frequency and increased the amplitude at 6 and 14 but not 9 DIV. There was no acute Ca2+ rise (Phase I response) in any age of HNG tested with TETS. These data demonstrated the importance of glia and developmental stage in modulating neuronal responses to TETS. Our results illustrate the applicability of the model for investigating how caged convulsants elicit abnormal network activity during the development of HN and HNG cultures in vitro.

KEYWORDS:

Calcium oscillations; Hippocampal neuronal network; Tetramethylenedisulfotetramine

PMID:
27984050
PMCID:
PMC5303550
DOI:
10.1016/j.neuro.2016.10.015
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center