Potential neuroprotective effects of 2-hydroxypropyl-? cyclodextrin against amyloid ? (1-42)-induced neurotoxicity on the rat hippocampus

The neurodegenerative mechanisms of Alzheimer's disease (AD) are not fully understood, but it is believed that amyloid beta (A beta) peptide causes oxidative stress, neuroinflammation, and disrupts metabotropic glutamate receptor 5 (mGluR5) signaling by interacting with cholesterol and caveolin-1 (Cav-1) in pathogenic lipid rafts. This study examined the effect of 2-hydroxypropyl-beta-cyclodextrin (HP-CD) on cholesterol, oxidative stress (total oxidant status), neuroinflammation (TNF-alpha), and mGluR5 signaling molecules such as PKC beta 1, PKC beta 2, ERK1/2, CREB, BDNF, and NGF in A beta (1-42)-induced neurotoxicity. The Sprague-Dawley rats were divided into four groups: control (saline), A beta (1-42), HP-CD (100 mg/kg), and A beta (1-42) + HP-CD (100 mg/kg). All groups received bilateral stereotaxic injections of A beta (1-42) or saline into the hippocampus. After surgery, HP-CD was administered intraperitoneally (ip) for 7 days. Cholesterol, TNF-alpha, and TOS levels were measured in synaptosomes isolated from hippocampus tissue using spectrophotometry, fluorometry, and enzyme immunoassay, respectively. The gene expressions of Cav-1, mGluR5, PKC beta 1, PKC beta 2, ERK1/2, CREB, BDNF, and NGF in hippocampus tissue were evaluated using reverse transcription PCR after real-time PCR analysis. Treatment with A beta (1-42) significantly elevated cholesterol, TOS, TNF-alpha, Cav-1, PKC beta 2, and ERK1/2 levels. Additionally, mGluR5, CREB, and BDNF levels were shown to be lowered. HP-CD reduced cholesterol, TOS, and TNF-alpha levels while increasing mGluR5, CREB, and BDNF in response to A beta (1-42) treatment. These findings indicate that HP-CD may have neuroprotective activity due to the decreased levels of cholesterol, oxidative stress, and neuroinflammation, as well as upregulated levels of mGluR5, CREB, and BDNF.