AbdEl-Raouf_2024_J.Alzheimers.Dis__13872877241295405

BACKGROUND: Alzheimer's disease (AD) is a progressive and irreversible neurological disorder that gradually deteriorates an individual's ability to carry out even the simplest tasks. OBJECTIVE: This study was undertaken to investigate the potential therapeutic efficacy of a novel bithiophene in a rat model of aluminum-induced AD pathology. METHODS: A total of 108 adult male albino rats weighing 160 +/- 20 g, were randomly assigned to six groups: (1) a control group administered DMSO, (2) group receiving a high dose of bithiophene (1 mg/kg), (3) a model group received AlCl(3) (100 mg/kg), those rats were then treated by either (4) bithiophene low dose (0.5 mg/kg), (5) high dose (1 mg/kg), or (6) memantine (20 mg/kg). RESULTS: Low dose bithiophene treatment was a promising strategy for mitigating oxidative stress and improving synaptic plasticity. This was demonstrated by reductions in malondialdehyde level, and increased activities of superoxide dismutase and catalase, and elevated glutathione content. Likewise, low dose bithiophene enhanced synaptic plasticity through a reduction in excitatory glutamate and norepinephrine levels, while increasing dopamine. Moreover, bithiophene significantly downregulated the expression of GSAP, GSK3-beta, and p53, which are implicated in AD progression. This treatment also decreased caspase 3 and amyloid-beta (Abeta(1-42)) accumulation in the hippocampus. Finally, behavioral assessments revealed that low dose bithiophene significantly enhanced learning abilities, as proved by Morris water maze. CONCLUSIONS: Low dose bithiophene mitigated AD through ameliorating oxidative stress, promoting synaptic plasticity, inhibiting the Abeta accumulation, and enhancing the cognitive functions in a rat model.