title: Regulation of neuronal and glial proteins by leptin: implications for brain development.
abstract: 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.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Ahima
authors.forename: C
authors.initials: C
authors.lastname: Bjorbaek
authors.forename: S
authors.initials: S
authors.lastname: Osei
authors.forename: J S
authors.initials: JS
authors.lastname: Flier
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001921:Brain / Q000187:drug effects / Q000254:growth & development*; D005260:Female; D019922:GAP-43 Protein / Q000032:analysis; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D020738:Leptin; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000032:analysis*; D011506:Proteins / Q000494:pharmacology*; D016708:Synaptophysin / Q000032:analysis; D050827:Syntaxin 1
chemical_list: D000954:Antigens, Surface; D019922:GAP-43 Protein; D005904:Glial Fibrillary Acidic Protein; D020738:Leptin; D009419:Nerve Tissue Proteins; D011506:Proteins; C494214:Stx1a protein, mouse; D016708:Synaptophysin; D050827:Syntaxin 1