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Metabolic brain disease1994; 9(4); 333-345; doi: 10.1007/BF02098880

Effect of serum on intracellular calcium homeostasis and survival of primary cortical and hippocampal CA1 neurons following brief glutamate treatment.

Abstract: Glutamate neurotoxicity was studied in primary neuronal cultures prepared from rat cerebral cortex and hippocampal CA1 sector. Neurons were cultivated with 5% native horse serum and then exposed to 0.1 or 1.0 mM glutamate for 5 min. Subsequently, neurons were allowed to recover for 24 hours either in the presence or in the absence of 5% native horse serum. In the absence of serum, neurons showed morphological signs of degeneration and exhibited marked loss of vitality as tested by vital staining and release of lactate dehydrogenase (LDH). In contrast, when neurons were cultivated in the presence of serum, no degenerative changes were seen and the neurons survived. Heat inactivated serum did not prevent neuronal death but addition of basic fibroblast growth factor (bFGF) or transforming growth factor-beta 1 (TGF-beta 1) had the same protective effect as native serum. Measurements of intracellular calcium activity ([Ca2+]i) with the indicator dye fura-2 revealed a sharp increase during glutamate exposure. In the absence of serum, [Ca2+]i returned to near control within 5 min but it secondarily increased after 1 hour to almost the same level as during glutamate exposure. This delayed increase was more pronounced in CA1 than in cortical neurons, it correlated linearly with the initial rise during glutamate exposure, and it was greatly reduced in the presence of serum. These observations suggest that glutamate neurotoxicity in vitro is a function of the delayed and not of the primary rise of intracellular calcium activity, and that trophic factors prevent neurotoxicity by attenuating this delayed response.
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Publication Date: 1994-12-01 PubMed ID: 7898400DOI: 10.1007/BF02098880Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article studies the damaging effects of the neurotransmitter glutamate in brain neurons and how these effects may be alleviated with the presence of serum. It also discusses the potential neuroprotective qualities of certain growth factors.

Research Context and Method

  • The focus of the research was on glutamate neurotoxicity, which occurs when excess glutamate destroys neurons in the brain.
  • The researchers used primary neuronal cultures from rat cerebral cortex and hippocampal CA1 sector for the experiment.
  • The neural cells were cultured with 5% native horse serum and then exposed to certain concentrations of glutamate.
  • Following the exposure, the neurons were either allowed to recover in the presence or absence of serum for 24 hours.

Findings

  • When there was no serum present during recovery, the neurons exhibited signs of degeneration and a significant loss of vitality. This was tested by using vital staining and assessing the release of lactate dehydrogenase (LDH), a marker for cellular damage.
  • However, when serum was present, the neurons showed no signs of degeneration and survived.
  • Heat inactivating the serum did not prevent neuronal death, indicating the role of bioactive compounds in protection.

Role of Growth Factors

  • Adding fundamental growth factors like basic fibroblast growth factor (bFGF) or transforming growth factor-beta 1 (TGF-beta 1) replicated the protective effect of the native serum.
  • This suggests that the serum was providing trophic factors which helped prevent neurotoxic effects.

Role of Calcium

  • Measurements of intracellular calcium activity with the indicator dye fura-2 showed a sharp increase during glutamate exposure.
  • In the absence of serum, the calcium activity returned to near control levels but increased again after an hour.
  • This delayed increase was more noticeable in some neurons than others, and it was significantly reduced in the presence of serum.
  • The researchers concluded that the toxic effects of glutamate were correlated more with the delayed rise in intracellular calcium levels, rather than the immediate rise in calcium levels after glutamate exposure.

Implications

  • The findings suggest a potential therapeutic avenue for conditions involving glutamate neurotoxicity, such as stroke or Alzheimer’s disease.
  • Further research into the nature of the trophic factors and calcium activity could yield applicable clinical strategies.

Cite This Article

APA
Uto A, Dux E, Hossmann KA. (1994). Effect of serum on intracellular calcium homeostasis and survival of primary cortical and hippocampal CA1 neurons following brief glutamate treatment. Metab Brain Dis, 9(4), 333-345. https://doi.org/10.1007/BF02098880

Publication

Metabolic brain disease
ISSN: 0885-7490
NlmUniqueID: 8610370
Country: United States
Language: English
Volume: 9
Issue: 4
Pages: 333-345

Researcher Affiliations

Uto, A
  • Max-Planck-Institute for Neurological Research, Department of Experimental Neurology, Cologne, Germany.
Dux, E
    Hossmann, K A

      MeSH Terms

      • Animals
      • Blood
      • Blood Proteins / physiology
      • Calcium / metabolism
      • Cell Death / drug effects
      • Cell Survival / drug effects
      • Cells, Cultured
      • Glutamic Acid / toxicity
      • Hippocampus / drug effects
      • Horses
      • L-Lactate Dehydrogenase
      • Nerve Degeneration
      • Neurons / drug effects
      • Neurons / metabolism
      • Rats
      • Rats, Wistar

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      Citations

      This article has been cited 1 times.
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