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Polysaccharides from Ganoderma lucidum attenuate cognitive impairment in 5xFAD mice by inhibiting oxidative stress
Xiaoqin Liu1, Yanbing Li2, Jiwei Wang2
1Institute of Brain Science, Medical School, Shanxi Datong University, Datong, 037009, China.
Abstract:
Oxidative stress and mitochondrial dynamics imbalance are key contributors to AD pathogenesis. GLPS, an extract from Ganoderma lucidum spores, exhibits anti-inflammatory, antioxidant, and immunomodulatory properties. However, the roles of GLPS in regulating oxidative stress and mitochondrial dynamics in AD remain poorly understood. Here, the underlying mechanisms of neuroprotective effects on cognitive dysfunction in 5 × FAD mice were explored. C57BL/6 mice served as WT controls, while 5 × FAD mice were divided into an AD group and an AD + GLPS group. The mice in AD + GLPS group were administered daily GLPS (25 mg/kg) by i.p. injection for two months, while WT and AD mice received an equivalent volume of normal saline. The results indicated that GLPS markedly improved cognitive function and decreased p-tau and Aβ levels in 5 × FAD mice. Moreover, GLPS alleviated oxidative stress by increasing SOD levels and decreasing MDA concentrations. It also inhibited excessive mitochondrial fragmentation by decreasing the expression of p-Drp1 and Fis1, while increasing the levels of Mfn1, Mfn2, and OPA1 in 5 × FAD mice. Mechanistically, GLPS activated Nrf2, leading to a marked upregulation of antioxidant enzymes, including HO- 1, NQO1, and SOD2 in 5 × FAD mice. Collectively, these findings suggest that GLPS ameliorates cognitive deficits in 5 × FAD mice by reducing oxidative stress and modulating mitochondrial dynamics through Nrf2-mediated antioxidant enzyme activation.
Insights
Ganoderma lucidum spores extract (GLPS) improves cognitive function in Alzheimer's disease (AD) models by reducing oxidative stress and normalizing mitochondrial dynamics. GLPS activates the Nrf2 pathway, enhancing antioxidant defenses for neuroprotection.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Oxidative stress and imbalanced mitochondrial dynamics are central to Alzheimer's disease (AD) pathogenesis.
- Ganoderma lucidum spores (GLPS) possess antioxidant and anti-inflammatory properties, but their role in AD neuroprotection is unclear.
- Understanding GLPS's mechanisms in regulating oxidative stress and mitochondrial function in AD is crucial.
Purpose of the Study:
- To investigate the neuroprotective mechanisms of GLPS on cognitive dysfunction in a mouse model of Alzheimer's disease (5x FAD mice).
- To explore GLPS's effects on oxidative stress markers and mitochondrial dynamics in the 5x FAD mouse model.
- To elucidate the molecular pathways, specifically Nrf2 activation, underlying GLPS's therapeutic potential.
Main Methods:
- 5x FAD mice and wild-type (WT) C57BL/6 mice were used. 5x FAD mice were divided into AD and AD + GLPS groups.
- GLPS (25 mg/kg) was administered via intraperitoneal injection daily for two months to the AD + GLPS group.
- Cognitive function, amyloid-beta (Aβ) and phosphorylated tau (p-tau) levels, oxidative stress markers (SOD, MDA), mitochondrial dynamics proteins (p-Drp1, Fis1, Mfn1, Mfn2, OPA1), and Nrf2 pathway components (HO-1, NQO1, SOD2) were assessed.
Main Results:
- GLPS treatment significantly improved cognitive function in 5x FAD mice.
- GLPS reduced levels of p-tau and Aβ, alleviated oxidative stress (increased SOD, decreased MDA), and inhibited mitochondrial fragmentation (decreased p-Drp1, Fis1; increased Mfn1, Mfn2, OPA1).
- GLPS activated the Nrf2 pathway, upregulating antioxidant enzymes HO-1, NQO1, and SOD2.
Conclusions:
- GLPS demonstrates significant neuroprotective effects against cognitive deficits in the 5x FAD mouse model.
- GLPS ameliorates AD pathology by mitigating oxidative stress and normalizing mitochondrial dynamics.
- The therapeutic benefits of GLPS are mediated through the activation of the Nrf2-dependent antioxidant pathway.
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