TY - JOUR
T1 - Regulation of neuronal and glial proteins by leptin
T2 - Implications for brain development
AU - Ahima, Rexford S.
AU - Bjorbæk, Christian
AU - Osei, Suzette
AU - Flier, Jeffrey S.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
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U2 - 10.1210/endo.140.6.6774
DO - 10.1210/endo.140.6.6774
M3 - Article
C2 - 10342866
AN - SCOPUS:17744375347
SN - 0013-7227
VL - 140
SP - 2755
EP - 2762
JO - Endocrinology
JF - Endocrinology
IS - 6
ER -