Human Cerebrospinal Fluid Promotes Neuronal Viability and Activity of Hippocampal Neuronal Circuits In Vitro

Front. Cell. Neurosci., 2016 · DOI: 10.3389/fncel.2016.00054 · Published: March 4, 2016

Simple Explanation

The study investigates how human cerebrospinal fluid (hCSF) affects neuronal circuits in vitro, comparing neuronal morphology, viability, and electrophysiological function in rat organotypic slice and primary neuronal cultures cultivated in hCSF versus standard culture media. Rodent hippocampal slices and primary neurons cultured in hCSF maintain neuronal morphology and synaptic transmission. hCSF increases neuronal viability and the number of electrophysiologically active neurons compared to culture media. The findings indicate that hCSF is a more physiological environment for neurons in vitro than standard media, offering a novel strategy for central nervous system (CNS) disease modeling and assessing the functional consequences of CSF on neuronal circuits.

Study Duration

9 days

Participants

Human CSF samples from 8 individuals (4 female, 4 male, age > 60 years) and Wistar rats (P7-10)

Evidence Level

Not specified

Key Findings

1
hCSF increases neuronal viability and the number of electrophysiologically active neurons compared to standard culture media in rat hippocampal slices and primary neurons.
2
Mature rat hippocampal neuronal cultures exposed to hCSF showed a gradual increase in spiking activity, with low-active cultures converting into high-active ones within 72 hours.
3
Organotypic hippocampal slices cultured in hCSF exhibited significantly less expression of caspase-3/7, indicating less apoptotic cell death, compared to those cultured in Nb-A.

Research Summary

This study presents an in vitro approach to assess the influence of human cerebrospinal fluid (hCSF) on neuronal circuits by examining survival, morphology, and network properties of hippocampal neurons. Results indicate that hCSF enhances neuronal function, viability, and preserves synaptic transmission in hippocampal organotypic slice cultures and primary neuronal cultures, outperforming standard culture media. The findings suggest that hCSF provides a more physiological environment for in vitro neuronal cultures and could be valuable for developing better culture conditions and disease models for the central nervous system.

Practical Implications

Improved Culture Conditions

hCSF can serve as a superior culture condition compared to defined standard media for in vitro neuronal studies.

Disease Modeling

The experimental approach paves the way to assess the functional consequences of CSF on neuronal circuits as well as suggesting a novel strategy for central nervous system (CNS) disease modeling.

Biomarker Identification

Combining hCSF-based in vitro approaches with CSF-biomarker screening could efficiently identify factors in the CSF that influence neuronal function, aiding the development of physiological culture media and brain disease models.

Study Limitations

1
The study uses rodent-based in vitro models with human CSF, which might not perfectly replicate human brain pathophysiology.
2
The exact supportive factors in hCSF promoting neuronal viability and activity remain unidentified.
3
The long-term effects of hCSF exposure on neuronal circuits beyond 9 days were not explored.

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