Age- and sex-associated changes in mRNA expression of neurodegenerative disorder-related molecules in the hippocampus and cerebellum of rat brain.

摘要

Age-associated oxidative stress is involved in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, and sex-associated differences may also affect the risk for these neurodegenerative diseases. We compared the effects of aging and sex on the mRNA expression of five molecules that are closely related to oxidative stress, along with Alzheimer's and Parkinson's diseases in the hippocampus of both male and female Fischer 344xBrown Norway (F344BN) rats. The reverse transcription polymerase chain reaction was used to determine the mRNA expression level of superoxide dismutase 2 (SOD2), heme oxygenase 1 (HO1), amyloid precursor protein (APP), beta-site APP-cleaving enzyme 1 (BACE1), and alpha-synuclein (ASN) in the hippocampus of 3 groups of male and female (young rats, aged rats, and very aged F344BN rats). No significant age- or sex-related changes were observed in the expression levels of SOD2, APP, or BACE1 mRNAs. The expression of HO1 mRNA in the very aged female rat hippocampus was significantly higher than that observed in the young female control and the aged females, when compared to male counterparts. No significant age-associated changes were observed in the expression of ASN mRNA; however, the expression of ASN was significantly higher in the hippocampus of male compared to female rats. Because the accumulation of iron in the brain plays a key role in Alzheimer's and Parkinson's diseases, we also investigated age- and sex-related expression of five mRNAs that are closely related to iron storage, transportation, and metabolism: ferritin heavy chain (FTH), ferritin light chain (FTL), transferrin receptor (TfR), divalent metal transporter 1 (DMT1), and iron-regulatory protein 1 (IRP1). No significant age-related changes were observed in the expression levels of any of these five molecules. The overall expression of FTH and IRP1 mRNAs was significantly lower in the hippocampus of male rats when compared to females. This study paves the way for the further investigation of age- and sex-related changes in the protein expression and activities of these molecules, and will help clarify the mechanisms by which oxidative damage may affect neurodegenerative diseases.