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. 2025 May 15;27(1):34.
doi: 10.1007/s12017-025-08860-2.

Far-Infrared Radiation Ameliorates the Cognitive Dysfunction in an Alzheimer's Disease Transgenic Mouse via Modulating Jak-2/Stat3 and Nrf-2/HO-1 Pathways

Wen Yang  1 , Qiuxia Yu  1 , Nick Wang  2 , Koon Kit Lam  1 , Zhi-Xiu Lin  3   4 , Yan-Fang Xian  5
Affiliations

Far-Infrared Radiation Ameliorates the Cognitive Dysfunction in an Alzheimer's Disease Transgenic Mouse via Modulating Jak-2/Stat3 and Nrf-2/HO-1 Pathways

Wen Yang et al. Neuromolecular Med. .

Abstract

Alzheimer's disease (AD) is the primary cause of dementia in the elderly. However, effective therapies that modify the disease process in AD remain elusive. Far-infrared radiation (FIR) is commonly utilized as a complementary treatment a range of disease, for example insomnia and rheumatoid arthritis. In this research, we explored how FIR light impacts the cognitive functions of TgCRND8 AD mice and elucidated its underlying molecular mechanism. The cognitive capabilities of TgCRND8 mice assessed by employing the Morris water maze. The concentrations of IL-1β, TNF-α, IL-4, Aβ40, and Aβ42 protein were assessed by enzyme-linked immunosorbent assay. Immunostaining was conducted to assess the Aβ deposits and microglial presence in the brains of TgCRND8 mice. Western blot was applied to detect the protein expressions of tau phosphorylation, amyloid-β (Aβ) production, Jak-2/Stat3, and Nrf-2/HO-1 pathways. The results indicated that FIR light notably ameliorated the cognitive impairments of the AD mice, reduced both Aβ deposition and tau protein hyperphosphorylation at sites of Thr205, Ser369, Ser404, and Thr181, suppressed the release of TNF-α and IL-1β, attenuated the ratios of p-Jak-2/Jak-2 and p-Stat3/Stat3, while increased the protein levels of IL-4, Nrf-2, and HO-1 in the brains of TgCRND8 mice. These findings amply demonstrated that FIR light ameliorated cognitive deficits of TgCRND8 mice via reducing both Aβ burden and tau protein hyperphosphorylation, suppressing the neuroinflammation, and restoring the levels of the oxidative-related proteins through modulating Jak-2/Stat3 and Nrf-2/HO-1 pathways. These experimental findings indicate that FIR light treatment is a promising treatment approach for AD.

Keywords: Alzheimer’s disease; Cognitive dysfunction; Far-infrared radiation; Jak-2/Stat3 pathway; Nrf-2/HO-1 pathway; TgCRND8 mice.

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Conflict of interest statement

Declaration. Conflict of interest: The authors declare no competing interests. Consent for Publication: All authors have consented for publication.

Figures

Fig. 1
Fig. 1
FIR light treatment ameliorated the learning and memory deficits of TgCRND8 mice. A Treatment schedule of FIR light on the TgCRND8 mice. B Escape latency of the mice to find the platform in training trial. C The time of the mice spent in the quadrant which contain the platform in the prob test. D Representative tracking routes of mice in the probe test. E The mean swimming speed of the mice in the prob test. Data were means ± SEM (n = 6). *p < 0.05; ns, not significant
Fig. 2
Fig. 2
FIR light treatment ameliorated Aβ deposition and cytokine expression in the cortex and the hippocampus of the brains. A, B Representative images of Aβ staining in the cerebral cortex and the hippocampus from the WT, TgCRND8 and FIR light-treated TgCRND8 mice. C Aβ plaque density in the cerebral cortex and the hippocampus of the mice (n = 3). D The ratio of levels of Aβ42/Aβ40 of the cerebral cortex of the mice (n = 6). E Density of Iba-1 positive microglia in the cerebral cortex and the hippocampus of the mice (n = 3). F–H The levels of IL-1β, TNF-α, and IL-4 of the cerebral cortex of the mice (n = 6). Data were means ± SEM. *p < 0.05, **p < 0.01 and ***p < 0.001. ns not significant
Fig. 3
Fig. 3
FIR light treatment modulated Aβ production and clearance in the cortex and the hippocampus of the brains. A The Western blot analysis of key molecules involved in the process of Aβ production in hippocampus of the mice. B Expression levels of p-APP, BACE-1 and ADAM-10 in the hippocampus of the mice. C The Western blot analysis of the key molecules involved in the process of Aβ production in the hippocampus of the mice. D Expression levels of p-APP, BACE-1 and IDE-1 in the cortex of the mice. Data were means ± SEM, *p < 0.05, **p < 0.01, and ***p < 0.001
Fig. 4
Fig. 4
FIR light treatment reduced the phosphorylation of tau protein in the cortex and the hippocampus. A The Western blot analysis of phosphorylated tau protein in the hippocampus of the mice. B Expression levels of p-tau Thr205, p-tau Ser369, and p-tau Ser404 and p-tau Thr181 in the hippocampus of the mice. C The Western blot analysis of phosphorylated tau protein in cortex of the mice. D Expression levels of p-tau (Thr205), p-tau (Ser369), and p-tau (Ser404) and p-tau (Thr181) in the cortex of the mice. Data were means ± SEM, *p < 0.05, **p < 0.01 and ****p < 0.0001. ns not significant
Fig. 5
Fig. 5
FIR light treatment modulated the expression of Jak-2/Stat3 and Nrf-2/HO-1 signaling in the TgCRND8 mice. A The Western blot analysis of Jak-2/Stat3 and Nrf-2/HO-1 in the hippocampus of the mice. B Expression levels of Nrf-2, HO-1 in the hippocampus of the mice. C Expression levels of p-Jak2/Jak2, p-Stat3/Stat3 in the hippocampus of the mice. D The Western blot analysis of Jak-2 and Nrf-2/HO-1 in the cortex of the mice. E Expression levels of Nrf-2, HO-1 in the cortex of the mice. F Expression levels of p-Jak2/Jak2 in the cortex of the mice. Data were means ± SEM. *p < 0.05, **p < 0.01 and ****p < 0.0001
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