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Mossy fiber expression of αSMA in human hippocampus and its relevance to brain evolution and neuronal development

Tian Tu1,2, Xiao-Lu Cai2, Zhong-Ping Sun2

  • 1Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.

Scientific Reports
|May 6, 2025
PubMed

Insights

Alpha-smooth muscle actin (αSMA) is newly found in human hippocampal mossy fibers, unlike in rodents. This protein’s expression refines during human brain development, suggesting a role in hippocampal evolution.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Developmental Biology

Background:

  • Alpha-smooth muscle actin (αSMA) is primarily known as a component of smooth muscle cells.
  • A novel immunolabeling pattern of αSMA was observed in adult human hippocampal mossy fibers (MF).

Purpose of the Study:

  • To investigate the phylogenic and ontogenic distribution of αSMA in the hippocampus.
  • To explore the novel finding of αSMA in human hippocampal mossy fibers.

Main Methods:

  • Immunolabeling of αSMA in human and various animal hippocampi across different ages.
  • Analysis of αSMA expression during human brain development (prenatal to infancy).
  • Validation of αSMA antibody specificity using ACTA2 siRNA in neuronal cell cultures.
  • Quantification of αSMA protein levels in different human brain regions.

Main Results:

  • Distinct αSMA immunolabeling was found in human hippocampal MF terminals from infancy to elderly.
  • This pattern was absent in mice and rats, but present in guinea pigs, cats, and Rhesus monkeys.
  • Human hippocampal αSMA expression emerged during the last trimester of gestation and refined through early infancy.
  • Higher αSMA protein levels were detected in the human dentate gyrus compared to other brain areas.

Conclusions:

  • αSMA is distinctly expressed in human hippocampal mossy fibers, a pattern not conserved across all mammals.
  • The observed pattern suggests a link between αSMA expression, hippocampal evolution, and mammalian brain development.
  • Refinement of neuronal αSMA expression during human brain development is a key finding.
Keywords:
Actin isoformsBrain developmentMammalian evolutionSynaptoplasticityTrisynaptic circuit

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