Alpha-synuclein expression in anterior pituitary cells of aged cattle

Abstract

The anterior pituitary (AP) gland must function properly for homeostasis and fertility; however, aging suppresses AP function via unclear mechanisms. α-synuclein is a protein encoded by the SNCA gene. Its monomers aggregate to the fibril form, which causes brain disease as age advances. Importantly, fibril α-synuclein propagates among neurons akin to prions. Recently, we discovered α-synuclein expression in oxytocin neurons and gonadotrophin-releasing hormone (GnRH) neurons in bovine hypothalamus. However, whether α-synuclein propagates into gonadotrophs remains unclear. We tested the hypothesis that α-synuclein expression in AP glands of aged cows is different from that of healthy heifers. We analyzed mRNA and protein levels and performed fluorescent immunohistochemistry for luteinizing hormone, follicle-stimulating hormone, GnRH receptor, and α-synuclein, followed by confocal microscopy with Congo red staining to detect amyloid deposits. Presence of synuclein was confirmed in AP tissues by both mRNA and protein levels in both heifers and old cows. Western blots showed several bands of α-synuclein, probably reflecting monomer, dimer, and oligomers, in the AP tissues of both heifers and old cows. Confocal microscopy revealed that most gonadotrophs were positive for both α-synuclein and Congo red in the old group, but not in the young group. In addition, α-synuclein expression was detected in the immortalized gonadotrophs, LβT2 cells, and in the majority of aged bovine corticotrophs, lactotrophs, somatotrophs, and thyrotrophs. In conclusion, the majority of gonadotrophs and other AP cell types were positive for α-synuclein and amyloid deposits in the old group, but not in the young group.