Regulation of neuronal and glial proteins by leptin: implications for brain development

Endocrinology. 1999 Jun;140(6):2755-62. doi: 10.1210/endo.140.6.6774.


The complete absence of leptin causes severe obesity in mice and humans, but its physiological roles are incompletely defined. Earlier studies reported decreased brain weight and impaired myelination in ob/ob and db/db mice. Here we have examined the effects of leptin deficiency and postnatal leptin treatment on brain weight, the expression of a broad array of neuronal and glial markers, and locomotor activity. ob/ob and db/db mice have reduced brain weight and an immature pattern of expression of synaptic and glial proteins, with growth-associated protein being elevated in the neocortex and hippocampus, and syntaxin-1, synaptosomal-associated protein-25, and synaptobrevin being decreased. The expression of myelin basic protein, proteolipid protein, and glial fibrillary acidic protein was also decreased in the neocortex, hippocampus, and striatum of ob/ob and db/db mice. Six weeks of leptin treatment initiated at week 4 increased brain weight and protein content, increased locomotor activity, and normalized levels of growth-associated protein, syntaxin-1, and synaptosomal-associated protein-25 in ob/ob mice without affecting synaptobrevin and glial proteins. In contrast with ob/ob and db/db mice, obese agouti (AY/a) mice had normal brain weight and expression of synaptic and glial proteins. These findings suggest that leptin, a peripheral signal of energy stores in adult animals, is required for normal neuronal and glial maturation in the mouse nervous system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Surface / analysis
  • Brain / drug effects
  • Brain / growth & development*
  • Female
  • GAP-43 Protein / analysis
  • Glial Fibrillary Acidic Protein / biosynthesis
  • Leptin
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Motor Activity / drug effects
  • Nerve Tissue Proteins / analysis*
  • Proteins / pharmacology*
  • Synaptophysin / analysis
  • Syntaxin 1


  • Antigens, Surface
  • GAP-43 Protein
  • Glial Fibrillary Acidic Protein
  • Leptin
  • Nerve Tissue Proteins
  • Proteins
  • Stx1a protein, mouse
  • Synaptophysin
  • Syntaxin 1