Age and Sex-Related Changes to Gene Expression in the Mouse Spinal Cord

J Mol Neurosci. 2019 Nov;69(3):419-432. doi: 10.1007/s12031-019-01371-3. Epub 2019 Jul 2.

Abstract

The spinal cord is essential for neuronal communication between the brain and rest of the body. To gain further insight into the molecular changes underpinning maturation of the mouse spinal cord, we analysed gene expression differences between 4 weeks of age (prior to puberty onset) and adulthood (8 weeks). We found 800 genes were significantly differentially expressed between juvenile and adult spinal cords. Gene ontology analysis revealed an overrepresentation of genes with roles in myelination and signal transduction among others. The expression of a further 19 genes was sexually dimorphic; these included both autosomal and sex-linked genes. Given the presence of steroid hormone receptors in the spinal cord, we also looked at the impact of two major steroid hormones, oestradiol and dihydrotestosterone (DHT) on spinal cord gene expression for selected genes. In gonadectomised male animals, implants with oestradiol and DHT produced significant changes to spinal cord gene expression. This study provides an overview of the global gene expression changes that occur as the spinal cord matures, over a key period of maturation. This confirms that both age and sex are important considerations in studies involving the spinal cord.

Keywords: Adult; Juvenile; Oestradiol; RNA-seq; Sex differences; Spinal cord; Testosterone.

MeSH terms

  • Aging / genetics
  • Aging / metabolism*
  • Animals
  • Castration
  • Dihydrotestosterone / administration & dosage
  • Dihydrotestosterone / pharmacology
  • Drug Implants
  • Estradiol / administration & dosage
  • Estradiol / pharmacology
  • Female
  • Gene Expression Regulation* / drug effects
  • Gene Ontology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myelin Sheath / physiology
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics*
  • RNA, Messenger / biosynthesis
  • Sex Characteristics*
  • Sexual Maturation
  • Signal Transduction / genetics
  • Spinal Cord / growth & development
  • Spinal Cord / metabolism*
  • Transcription, Genetic

Substances

  • Drug Implants
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Dihydrotestosterone
  • Estradiol