Expression of Sortilin 1-like immunoreactive proteins, an endocytic receptor for pathogenic α-synuclein fibrils, in bovine GnRH neurons: observations in young and aged animals

CONTEXT: Ageing is associated with reduced fertility, yet the neuronal basis of reproductive decline remains poorly understood. Alpha-synuclein (αSYN), a protein implicated in neurodegeneration, accumulates in bovine gonadotrophin-releasing hormone (GnRH) neurons during ageing. Sortilin 1 (SORT1), an endocytic receptor for pathogenic αSYN fibrils, may be relevant to this process. AIMS: To examine SORT1 expression in hypothalamic GnRH neurons of young heifers and aged cows, and to assess possible regional and age-related differences. METHODS: SORT1 mRNA and protein were analysed by RT-PCR, quantitative RT-PCR, and western blotting in bovine cortex, hippocampus, and hypothalamic regions, including the preoptic area (POA), arcuate nucleus (ARC), and median eminence (ME). Co-localisation with GnRH was examined by immunofluorescence and confocal microscopy. Expression was also examined in immortalised GnRH neurons (GT1-7). KEY RESULTS: SORT1 transcripts were detected in all brain regions examined and in GT1-7 cells. Western blotting revealed multiple SORT1-like immunoreactive bands in each region, with overall stronger signals in the posterior hypothalamus (ARC and ME) of aged cows. Transcript levels showed no clear age-related differences. Confocal microscopy demonstrated SORT1-like immunoreactivity in GnRH-positive neurons in both age groups. CONCLUSION: Bovine GnRH neurons express SORT1-like immunoreactivity, indicating the presence of proteins related to SORT1 in these cells. The multiple immunoreactive bands observed may reflect isoforms, processing, or antibody cross-reactivity; however, their identities remain to be confirmed. IMPLICATIONS: These findings provide evidence for SORT1-like expression in bovine GnRH neurons, forming a basis for future studies on its potential role in reproductive ageing.