# Physical exercise/melatonin interaction in young rats fed a low-protein diet: a behavioral, electrophysiological, and redox balance analysis

**Authors:** Maria Luísa Figueira de Oliveira, Jennyfer Martins de Carvalho, José Anderson da Silva Gomes, Valéria Bianca de Souza Santos, Leucio Duarte Vieira Filho, Arthur Gabriel Alves Furtado de Carvalho Noya, Rubem Carlos Araujo Guedes

PMC · DOI: 10.3389/fnagi.2026.1740062 · Frontiers in Aging Neuroscience · 2026-02-06

## TL;DR

This study shows that melatonin and exercise can reduce brain and behavior problems in young rats with low-protein diets.

## Contribution

The study demonstrates complementary neuroprotective effects of melatonin and exercise in malnourished rats.

## Key findings

- Malnutrition increased anxiety, memory issues, and oxidative stress in rats.
- Melatonin and treadmill exercise reduced these effects and improved brain function.
- Combined interventions restored brain function closer to well-nourished rats.

## Abstract

Early-life protein malnutrition disrupts redox balance in the brain and alters brain development and function. This study evaluated the effects of subcutaneous melatonin (MLT) administration, treadmill exercise (TE), and their combination on behavioral parameters (anxiety and memory), brain electrical activity (cortical spreading depression, CSD), and brain oxidative stress in well-nourished (n = 40) and malnourished (n = 40) young male rats.

Both well-nourished and malnourished rats were assigned to treadmill exercise (n = 20) or sedentary (n = 20) groups. Each group (exercised and sedentary) received either MLT (subcutaneous; n = 10/group) or vehicle (n = 10/group). MLT (10 mg/kg on alternate days) and TE (forced running on a treadmill for 40-min daily sessions, 3 days/week) were conducted from P25 to P55. Immediately after TE and MLT treatments, animals underwent behavioral tests for anxiety (elevated plus maze and open field) and object recognition memory. CSD was continuously recorded for 4 h. Brains were collected for redox balance analyses.

Malnutrition increased anxiety-like behaviors, impaired memory, accelerated CSD propagation, and disrupted cortical redox balance. Both MLT administration and TE reduced these adverse effects, improving behavioral performance, slowing CSD, and attenuating prooxidant markers. The combined interventions produced values closer to those of well-nourished animals.

The data suggest that melatonin and aerobic exercise have complementary neuroprotective effects in malnourished young rats, mitigating behavioral and electrophysiological disturbances and restoring brain oxidative balance. These interventions may be promising strategies for minimizing the consequences of early-life protein malnutrition on neurodevelopment.

## Linked entities

- **Chemicals:** melatonin (PubChem CID 896)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Vegfa (vascular endothelial growth factor A) [NCBI Gene 83785] {aka VEGF-A, VEGF111, VEGF164, VPF, Vegf}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, Igf1 (insulin-like growth factor 1) [NCBI Gene 24482] {aka IGF}, Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, Bdnf (brain-derived neurotrophic factor) [NCBI Gene 24225]
- **Diseases:** RLU (MESH:D020795), demyelinating diseases (MESH:D003711), pain (MESH:D010146), AIN (MESH:D044342), reperfusion damage (MESH:D015427), autoimmune, and neurodegenerative diseases (MESH:D019636), inflammatory (MESH:D007249), damage to the central nervous system (MESH:D002493), Anxiety (MESH:D001007), dysbiosis (MESH:D064806), CSD (MESH:C562576), ischemic stroke (MESH:D002544), Alzheimer's (MESH:D000544), anxious behavior (MESH:D001523), migraine aura (MESH:D020325), EPM (MESH:D006937), CSD (MESH:D003866), breast cancer (MESH:D001943), EAE (MESH:D004681), neuronal damage (MESH:D009410), impaired memory (MESH:D008569), cognitive deficits (MESH:D003072), psoriasis (MESH:D011565), hyperactivity (MESH:D006948), ischemia (MESH:D007511), neurological and behavioral dysfunction (MESH:D009461), multiple sclerosis (MESH:D009103)
- **Chemicals:** methanol (MESH:D000432), MLT (MESH:D008550), NaCl (MESH:D012965), Superoxide (MESH:D013481), AIN (-), H2O2 (MESH:D006861), lucigenin (MESH:C033472), epinephrine (MESH:D004837), Malondialdehyde (MESH:D008315), trichloroacetic acid (MESH:D014238), corticosterone (MESH:D003345), NADPH (MESH:D009249), EDTA (MESH:D004492), adrenochrome (MESH:D000323), MDA (MESH:D015104), potassium phosphate (MESH:C013216), sulfhydryl (MESH:D013438), thiobarbituric acid (MESH:C029684), sodium carbonate (MESH:C005686), Lipid (MESH:D008055), L-cysteine (MESH:D003545), iron (MESH:D007501), GSH (MESH:D005978), alpha-chloralose (MESH:D002698), water (MESH:D014867), 1,1,3,3-tetraethoxypropane (MESH:C022168), ROS (MESH:D017382), ethanol (MESH:D000431), serotonin (MESH:D012701), TBARS (MESH:D017392), 5,5'-dithiobis(2-nitrobenzoic acid (MESH:D004228), acetic acid (MESH:D019342), SDS (MESH:D012967), ascorbic acid (MESH:D001205), urethane (MESH:D014520), KCl (MESH:D011189)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Cell lines:** AIN-93M — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_LM77), AIN-93 — Homo sapiens (Human), Nephropathic cystinosis, Finite cell line (CVCL_CW96), SH-SY5Y — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0019)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12920428/full.md

## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12920428/full.md

## References

70 references — full list in the complete paper: https://tomesphere.com/paper/PMC12920428/full.md

---
Source: https://tomesphere.com/paper/PMC12920428