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Beta-sitosterol mitigates cognitive deficit and hippocampal neurodegeneration in mice with trimethyltin-induced
Nurinee Dolrahman1, Wachiryah Thong-Asa1
1Animal Toxicology and Physiology Specialty Research Unit (ATPSRU), Department of Zoology, Faculty of Science, Kasetsart University, 50 Ngam Wong Wan Road, Jatujak, Bangkok 10900, Thailand.
Abstract:
The present study investigated the neural health benefit of beta-sitosterol (BSS) against trimethyltin (TMT)-induced neurodegeneration in mice. Forty male Institute of Cancer Research (ICR) mice were randomly divided into Sham-veh, TMT-veh, TMT-BSS50, and TMT-BSS100. A one-time intraperitoneal injection of 2.6 mg/kg of TMT was given to mice in TMT groups. Vehicle (veh), BSS 50 mg/kg or BSS 100 mg/kg were orally given for 2 weeks. Spatial learning and memory were evaluated. Brain oxidative status, hippocampal neuropathology, and reactive astrocytes were done. White matter pathology was also evaluated. The results indicated the massy effect of TMT on induced motor ability and spatial memory deficits in accordance with increased neuronal degeneration in Cornus ammonis (CA) 1, CA3, and dentate gyrus (DG) and internal capsule white matter damage. TMT also induced the reduction of reactive astrocytes in CA1 and DG. Brain's catalase activity was significantly reduced by TMT, but not in mice with BSS treatments. Both doses of BSS treatment exhibited improvement in motor ability and spatial memory deficits in accordance with the activation of reactive astrocytes in CA1, CA3, and DG. However, they successfully prevented the increase of neuronal degeneration in CA1 found only with the BSS dose of 100 mg/kg, and it was indicated as the effective dose for neuroprotection in the vulnerable brain area. This study demonstrated mitigative effects of BSS against motor ability and memory deficits with neural health benefits, including a protective effect against CA1 neurodegeneration and a nurturing effect on hippocampal reactive astrocytes.
Insights
Beta-sitosterol (BSS) shows neuroprotective effects against trimethyltin (TMT)-induced neurodegeneration. BSS treatment improved memory and motor function, with the 100 mg/kg dose effectively preventing neuronal damage in the hippocampus.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Trimethyltin (TMT) exposure causes neurodegeneration, impacting cognitive and motor functions.
- Oxidative stress and neuropathological changes, including white matter damage, are hallmarks of TMT toxicity.
- Reactive astrocytes play a crucial role in neuroinflammation and neuronal repair.
Purpose of the Study:
- To investigate the neuroprotective potential of beta-sitosterol (BSS) against TMT-induced neurotoxicity in mice.
- To evaluate the effects of BSS on spatial learning, memory, and neuropathology in a TMT mouse model.
- To determine the optimal dose of BSS for mitigating TMT-induced neural damage.
Main Methods:
- Male ICR mice were administered TMT intraperitoneally and treated orally with varying doses of BSS for two weeks.
- Assessment of spatial learning and memory using behavioral tests.
- Evaluation of brain oxidative status, hippocampal neuropathology, white matter integrity, and reactive astrocyte populations.
Main Results:
- TMT exposure significantly impaired motor ability and spatial memory, causing neuronal degeneration in the hippocampus (CA1, CA3, DG) and white matter damage.
- TMT treatment reduced catalase activity and altered reactive astrocyte levels in the hippocampus.
- BSS treatment, particularly at 100 mg/kg, ameliorated cognitive and motor deficits, preserved hippocampal astrocyte populations, and protected against CA1 neurodegeneration.
Conclusions:
- Beta-sitosterol (BSS) demonstrates significant neuroprotective effects against TMT-induced neurodegeneration.
- BSS treatment improves cognitive and motor functions by modulating oxidative stress and supporting hippocampal astrocyte activation.
- The 100 mg/kg dose of BSS is identified as an effective neuroprotective agent, particularly for vulnerable hippocampal regions like CA1.
