Journal of Pharmacology and Pharmaceutical Research

Research Article | J Pharmacol Pharm Res. 2018;1(1):002 | Open Access

---

Atorvastatin and Amyloid-Beta_1-40 Promote Differential Gene Expression of Proteins Involved on Glutamatergic Transmission in the Cerebral Cortex and Hippocampus

Wagner Carbolin Martins, Carolina Heyse Niebisch, Cláudia B Nedel and Carla Inês Tasca

  PDF 

Abstract

Deposition of amyloid-beta (Aβ) peptides into specific encephalic structures involved in learning and memory is an important event related to Alzheimer’s disease (AD) pathogenesis. As a consequence, deregulation of cellular processes such as glutamate transport, oxidative stress, neurotrophic factors levels may occur and cause synaptotoxicity and neuronal cell death. Herein, we evaluated the gene expression of proteins involved with the progression of AD. We aimed to assess an early event (after 24 h) of Aβ_1-40-induced toxicity in hippocampi and frontal cortices of mice. The effects of a pretreatment with atorvastatin, a HMG-CoA reductase inhibitor, in preventing Aβ_1-40-induced gene expression alterations were also evaluated. Atorvastatin (10 mg/kg/day, orally) was administered through 7 consecutive days before Aβ_1-40 administration. Atorvastatin treatment increases mRNA levels from NMDA receptor GluN1 subunit, PSD-95, BDNF and glutamate transporters (GLAST and GLT-1) in the cortex. In the hippocampus, atorvastatin did not alter glutamatergic genes (GluN1, PSD-95, GLT-1 and GLAST), but it reduced NOS1 and increased BDNF gene expression, what may be related to its neuroprotective action. Aβ_1-40 reduced gene expression of glutamatergic proteins and NOS1, but it increased BDNF mRNA levels, what might be interpreted as a compensatory response to Aβ_1-40 toxicity. Atorvastatin plus Aβ_1-40 treatment almost always show an opposite effect from the observed in Aβ_1-40-treated groups, reinforcing the data on the neuroprotective effect of atorvastatin against Aβ-induced toxicity even in early molecular alterations.

Keywords: Atorvastatin; Amyloid-β peptide; Glutamate; NMDA receptors; BDNF; Neuroprotection

Citation: 

Tasca CI, Martins WC, Niebisch CH, Nedel CB. Atorvastatin and Amyloid-Beta_1-40 Promote Differential Gene Expression of Proteins Involved on Glutamatergic Transmission in the Cerebral Cortex and Hippocampus. J Pharmacol Pharm Res. 2018;1(1):002