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Fasted-State Aerobic Exercise Enhances Cognition and Hippocampal BDNF Signaling in an Alzheimer's Disease Rat Model
Fatih Kirkbir, Taner Atasoy, Davar Khodadadai, Heidar Sajedi, Ozlem Keskin, Mohammad Babaie. Neurochemical research, 2025-12-20
Topic: Gut, metabolism and diet
Alzheimer's disease (AD) is a multifactorial disorder that demands a comprehensive management strategy. Both aerobic exercise training and intermittent fasting (IF) have been shown to ameliorate AD symptoms, yet the impact of exercise in the fasted state remains understudied. This study compared the effects of four weeks of moderate‑intensity treadmill running in either a fasted or a normal fed state on cognitive function and hippocampal BDNF signaling in an amyloid-β (Aβ)1-42-injected rat model of AD. Twenty‑month‑old male Wistar rats were allocated into five groups (n = 12 each): AD, AD plus IF (ADIF), AD plus exercise training (ADET), AD plus IF plus exercise training (ADIFET), and control. AD was induced by bilateral intra‑hippocampal Aβ1-42 injection. Exercise interventions (fasted or fed) were conducted 5 days/week for 4 weeks. Aβ injection significantly impaired learning and memory and reduced hippocampal levels of PKA, CREB, and BDNF (p < 0.001). Both fasting and exercise independently elevated plasma and hippocampal β-hydroxybutyrate (βHB) (p < 0.001), with the highest βHB increase observed in the fasted-exercise group (p < 0.01). All intervention groups (ADIF, ADET, and ADIFET) demonstrated significant improvements in cognitive performance and hippocampal levels of PKA, CREB, and BDNF (p < 0.001). The combined fasting plus exercise group produced greater benefits than either IF or exercise alone (p < 0.05), and exercise alone outperformed fasting alone (p < 0.05). These findings indicate that aerobic exercise in the fasted state offers superior neuroprotective and cognitive benefits, likely via upregulation of βHB/PKA/CREB/BDNF signaling, highlighting fasted‑state exercise as a promising therapeutic approach for AD.
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APA 7th
Kirkbir, F., Atasoy, T., Khodadadai, D., Sajedi, H., Keskin, O., & Babaie, M. (2025). Fasted-State Aerobic Exercise Enhances Cognition and Hippocampal BDNF Signaling in an Alzheimer's Disease Rat Model. Neurochemical research. https://doi.org/10.1007/s11064-025-04637-y
Vancouver
Kirkbir F, Atasoy T, Khodadadai D, Sajedi H, Keskin O, Babaie M. Fasted-State Aerobic Exercise Enhances Cognition and Hippocampal BDNF Signaling in an Alzheimer's Disease Rat Model. Neurochemical research. 2025. doi:10.1007/s11064-025-04637-y. PMID: 41420669.
BibTeX
@article{kirkbir2025-41420669,
author = {Kirkbir, Fatih and Atasoy, Taner and Khodadadai, Davar and Sajedi, Heidar and Keskin, Ozlem and Babaie, Mohammad},
title = {{Fasted-State Aerobic Exercise Enhances Cognition and Hippocampal BDNF Signaling in an Alzheimer's Disease Rat Model}},
journal = {Neurochemical research},
year = {2025},
doi = {10.1007/s11064-025-04637-y},
pmid = {41420669},
url = {https://doi.org/10.1007/s11064-025-04637-y}
}
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Key findings
- Aβ injection significantly impaired learning and memory and reduced hippocampal levels of PKA, CREB, and BDNF (p < 0.001).
- All intervention groups (ADIF, ADET, and ADIFET) demonstrated significant improvements in cognitive performance and hippocampal levels of PKA, CREB, and BDNF (p < 0.001).
- These findings indicate that aerobic exercise in the fasted state offers superior neuroprotective and cognitive benefits, likely via upregulation of βHB/PKA/CREB/BDNF signaling, highlighting fasted‑state exercise as a promising therapeutic approach for AD.
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Study details
- Participants12
- Evidence strengthLow
How this study scored 45/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 25 of the 56 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurochemical research) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 1 / 4 | 12 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “rat”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41420669) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 25 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 25 of the 56 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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