# Mild hypothermia enhances regenerative gene expression in late-stage neural precursors

**Authors:** Laura Dina Mitrečić, Eliana Eunjoo Park, Aya El-Hajj, Dinko Mitrečić

PMC · DOI: 10.3892/mi.2025.252 · Medicine International · 2025-07-16

## TL;DR

Mild hypothermia at a specific stage boosts regenerative genes in neural precursors, suggesting it could help treat brain injuries.

## Contribution

The study reveals that mild hypothermia at day 14 enhances regenerative gene expression in late-stage neural precursors.

## Key findings

- Mild hypothermia at day 14 preserves cell viability and increases Nestin expression.
- Mild hypothermia decreases Map2 expression, suggesting dedifferentiation.
- Ncam1 and Itgb1 genes are upregulated by mild hypothermia at day 14.

## Abstract

The present study investigated the effects of temperature modulation on neural precursors at various developmental stages. A well-proven neural stem cell model was employed and cells were exposed to hypothermia (32, 30 and 28˚C) and hyperthermia (39˚C) for periods of time. While deviations from the physiological temperature (37˚C) affected cell survival and generally reduced cell numbers, a distinct response was observed in late-stage precursors (day 14). Mild hypothermia (32˚C) at this stage preserved cell viability and increased the expression of Nestin, a marker of immature neuronal cells, while decreasing expression of the Map2, a marker of mature neurons. These combined findings suggest a potential dedifferentiation process and an enhanced regenerative capacity. Additionally, the levels of genes associated with cell adhesion, migration and differentiation (Ncam1 and Itgb1) were upregulated by mild hypothermia at day 14. On the whole, these findings highlight the differential response of neural precursors to temperature and suggest that hypothermia timing may be crucial for optimizing therapeutic strategies in neonatal brain injury.

## Linked entities

- **Genes:** nes.L (nestin L homeolog) [NCBI Gene 108699393], MAP2 (microtubule associated protein 2) [NCBI Gene 4133], NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684], ITGB1 (integrin subunit beta 1) [NCBI Gene 3688]

## Full-text entities

- **Genes:** POTEF (POTE ankyrin domain family member F) [NCBI Gene 728378] {aka A26C1B, POTE2alpha, POTEACTIN}, HPRT1 (hypoxanthine phosphoribosyltransferase 1) [NCBI Gene 3251] {aka HGPRT, HPRT}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, ITGB1 (integrin subunit beta 1) [NCBI Gene 3688] {aka CD29, FNRB, GPIIA, MDF2, MSK12, VLA-BETA}, Fgf2 (fibroblast growth factor 2) [NCBI Gene 14173] {aka Fgf-2, Fgf2a, Fgfb, bFGF}, MAP2 (microtubule associated protein 2) [NCBI Gene 4133] {aka MAP-2, MAP2A, MAP2B, MAP2C}, Map2 (microtubule-associated protein 2) [NCBI Gene 17756] {aka G1-397-34, MAP-2, Mtap-2, Mtap2, repro4}, Egf (epidermal growth factor) [NCBI Gene 13645], EPO (erythropoietin) [NCBI Gene 2056] {aka DBAL, ECYT5, EP, MVCD2}, CDH2 (cadherin 2) [NCBI Gene 1000] {aka ACOGS, ADHD8, ARVD14, CD325, CDHN, CDw325}, Nes (nestin) [NCBI Gene 18008] {aka ESTM46, Ifaprc2, Marc2, RC2}
- **Diseases:** DM (MESH:D009223), neuronal injury (MESH:D009410), Hypothermia (MESH:D007035), neonatal brain damage (MESH:D007232), glutamate (MESH:C537425), hypoxic (MESH:D002534), neurodevelopmental disabilities (MESH:D007859), dislocation (MESH:D004204), neurodevelopmental and behavioral disorders (MESH:D002653), impairment in (MESH:D060825), neurodegenerative and neuropsychiatric disorders (MESH:D019636), calcium overload (MESH:D019190), traumatic brain injury (MESH:D000070642), HIE (MESH:D020925), injury (MESH:D014947), inflammation (MESH:D007249), brain injury (MESH:D001930), stroke (MESH:D020521), hyperthermia (MESH:D005334), hypoxia (MESH:D000860), spinal cord injury (MESH:D013119)
- **Chemicals:** Pen (MESH:C058388), glutamate (MESH:D018698), melatonin (MESH:D008550), DAPI (MESH:C007293), streptomycin (MESH:D013307), KGaA (-), Alexa Fluor  488 (MESH:C000711379), PBS (MESH:D007854), calcium (MESH:D002118), N2 (MESH:D009584), Alexa Fluor  546 (MESH:C481052), oxygen (MESH:D010100), HEPES (MESH:D006531), penicillin (MESH:D010406)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Gallus gallus (bantam, species) [taxon 9031]
- **Mutations:** D14N, D14, D14H

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12312625/full.md

## References

44 references — full list in the complete paper: https://tomesphere.com/paper/PMC12312625/full.md

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Source: https://tomesphere.com/paper/PMC12312625