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Differential acute and chronic effects of leptin on hypothalamic astrocyte morphology and synaptic protein levels.

García-Cáceres C, Fuente-Martín E, Burgos-Ramos E, Granado M, Frago LM, Barrios V, Horvath T, Argente J, Chowen JA - Endocrinology (2011)

Bottom Line: Astrocytes participate in neuroendocrine functions partially through modulation of synaptic input density in the hypothalamus.Indeed, glial ensheathing of neurons is modified by specific hormones, thus determining the availability of neuronal membrane space for synaptic inputs, with the loss of this plasticity possibly being involved in pathological processes.However, acute leptin treatment reduced hypothalamic GFAP levels and induced synaptic protein levels 1 h after administration, with no effect on vimentin.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Avenida Menéndez Pelayo, 65, 28009 Madrid, Spain.

ABSTRACT
Astrocytes participate in neuroendocrine functions partially through modulation of synaptic input density in the hypothalamus. Indeed, glial ensheathing of neurons is modified by specific hormones, thus determining the availability of neuronal membrane space for synaptic inputs, with the loss of this plasticity possibly being involved in pathological processes. Leptin modulates synaptic inputs in the hypothalamus, but whether astrocytes participate in this action is unknown. Here we report that astrocyte structural proteins, such as glial fibrillary acidic protein (GFAP) and vimentin, are induced and astrocyte morphology modified by chronic leptin administration (intracerebroventricular, 2 wk), with these changes being inversely related to modifications in synaptic protein densities. Similar changes in glial structural proteins were observed in adult male rats that had increased body weight and circulating leptin levels due to neonatal overnutrition (overnutrition: four pups/litter vs. control: 12 pups/litter). However, acute leptin treatment reduced hypothalamic GFAP levels and induced synaptic protein levels 1 h after administration, with no effect on vimentin. In primary hypothalamic astrocyte cultures leptin also reduced GFAP levels at 1 h, with an induction at 24 h, indicating a possible direct effect of leptin. Hence, one mechanism by which leptin may affect metabolism is by modifying hypothalamic astrocyte morphology, which in turn could alter synaptic inputs to hypothalamic neurons. Furthermore, the responses to acute and chronic leptin exposure are inverse, raising the possibility that increased glial activation in response to chronic leptin exposure could be involved in central leptin resistance.

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Effect of chronic central leptin exposure on glial proteins and activation in the hypothalamus. Relative levels of GFAP (A), vimentin (B), and actin (C) in the hypothalamus of adult male Wistar rats treated icv for 14 d with either leptin (Lep; 15 μg/d) or vehicle (Ct; n = 6/group). Representative Western blots are shown for each protein. #, P < 0.05; *, P < 0.01. Results are represented as mean ± sem. Immunohistochemistry for vimentin in the arcuate nucleus of control (D and F) and leptin-treated rats (E and G) are shown. Quantitative analysis demonstrated a significant increase (***, P < 0.0001) in the number of vimentin fibers in the arcuate nucleus of leptin-treated rats (H). Vimentin-labeled astrocytes are clearly visible in leptin-treated rats (arrows). Scale bar, 40 μm (D and E); 20 μm (F and G).
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Figure 2: Effect of chronic central leptin exposure on glial proteins and activation in the hypothalamus. Relative levels of GFAP (A), vimentin (B), and actin (C) in the hypothalamus of adult male Wistar rats treated icv for 14 d with either leptin (Lep; 15 μg/d) or vehicle (Ct; n = 6/group). Representative Western blots are shown for each protein. #, P < 0.05; *, P < 0.01. Results are represented as mean ± sem. Immunohistochemistry for vimentin in the arcuate nucleus of control (D and F) and leptin-treated rats (E and G) are shown. Quantitative analysis demonstrated a significant increase (***, P < 0.0001) in the number of vimentin fibers in the arcuate nucleus of leptin-treated rats (H). Vimentin-labeled astrocytes are clearly visible in leptin-treated rats (arrows). Scale bar, 40 μm (D and E); 20 μm (F and G).

Mentions: As observed in overweight rats, there was a significant increase in both GFAP (Fig. 2A; P < 0.05) and vimentin (Fig. 2B; P < 0.01) in the hypothalamus of leptin-treated rats. In contrast, actin levels were decreased (Fig. 2C; P < 0.001). In leptin-treated rats (Fig. 2, E and G), there were visibly more vimentin-labeled fibers and astrocytes in the arcuate nucleus (Fig. 2, D and F), with quantitative analysis showing a significant increase in the number of vimentin-positive fibers in response to leptin (Fig. 2H; P < 0.0001).


Differential acute and chronic effects of leptin on hypothalamic astrocyte morphology and synaptic protein levels.

García-Cáceres C, Fuente-Martín E, Burgos-Ramos E, Granado M, Frago LM, Barrios V, Horvath T, Argente J, Chowen JA - Endocrinology (2011)

Effect of chronic central leptin exposure on glial proteins and activation in the hypothalamus. Relative levels of GFAP (A), vimentin (B), and actin (C) in the hypothalamus of adult male Wistar rats treated icv for 14 d with either leptin (Lep; 15 μg/d) or vehicle (Ct; n = 6/group). Representative Western blots are shown for each protein. #, P < 0.05; *, P < 0.01. Results are represented as mean ± sem. Immunohistochemistry for vimentin in the arcuate nucleus of control (D and F) and leptin-treated rats (E and G) are shown. Quantitative analysis demonstrated a significant increase (***, P < 0.0001) in the number of vimentin fibers in the arcuate nucleus of leptin-treated rats (H). Vimentin-labeled astrocytes are clearly visible in leptin-treated rats (arrows). Scale bar, 40 μm (D and E); 20 μm (F and G).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3860256&req=5

Figure 2: Effect of chronic central leptin exposure on glial proteins and activation in the hypothalamus. Relative levels of GFAP (A), vimentin (B), and actin (C) in the hypothalamus of adult male Wistar rats treated icv for 14 d with either leptin (Lep; 15 μg/d) or vehicle (Ct; n = 6/group). Representative Western blots are shown for each protein. #, P < 0.05; *, P < 0.01. Results are represented as mean ± sem. Immunohistochemistry for vimentin in the arcuate nucleus of control (D and F) and leptin-treated rats (E and G) are shown. Quantitative analysis demonstrated a significant increase (***, P < 0.0001) in the number of vimentin fibers in the arcuate nucleus of leptin-treated rats (H). Vimentin-labeled astrocytes are clearly visible in leptin-treated rats (arrows). Scale bar, 40 μm (D and E); 20 μm (F and G).
Mentions: As observed in overweight rats, there was a significant increase in both GFAP (Fig. 2A; P < 0.05) and vimentin (Fig. 2B; P < 0.01) in the hypothalamus of leptin-treated rats. In contrast, actin levels were decreased (Fig. 2C; P < 0.001). In leptin-treated rats (Fig. 2, E and G), there were visibly more vimentin-labeled fibers and astrocytes in the arcuate nucleus (Fig. 2, D and F), with quantitative analysis showing a significant increase in the number of vimentin-positive fibers in response to leptin (Fig. 2H; P < 0.0001).

Bottom Line: Astrocytes participate in neuroendocrine functions partially through modulation of synaptic input density in the hypothalamus.Indeed, glial ensheathing of neurons is modified by specific hormones, thus determining the availability of neuronal membrane space for synaptic inputs, with the loss of this plasticity possibly being involved in pathological processes.However, acute leptin treatment reduced hypothalamic GFAP levels and induced synaptic protein levels 1 h after administration, with no effect on vimentin.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Avenida Menéndez Pelayo, 65, 28009 Madrid, Spain.

ABSTRACT
Astrocytes participate in neuroendocrine functions partially through modulation of synaptic input density in the hypothalamus. Indeed, glial ensheathing of neurons is modified by specific hormones, thus determining the availability of neuronal membrane space for synaptic inputs, with the loss of this plasticity possibly being involved in pathological processes. Leptin modulates synaptic inputs in the hypothalamus, but whether astrocytes participate in this action is unknown. Here we report that astrocyte structural proteins, such as glial fibrillary acidic protein (GFAP) and vimentin, are induced and astrocyte morphology modified by chronic leptin administration (intracerebroventricular, 2 wk), with these changes being inversely related to modifications in synaptic protein densities. Similar changes in glial structural proteins were observed in adult male rats that had increased body weight and circulating leptin levels due to neonatal overnutrition (overnutrition: four pups/litter vs. control: 12 pups/litter). However, acute leptin treatment reduced hypothalamic GFAP levels and induced synaptic protein levels 1 h after administration, with no effect on vimentin. In primary hypothalamic astrocyte cultures leptin also reduced GFAP levels at 1 h, with an induction at 24 h, indicating a possible direct effect of leptin. Hence, one mechanism by which leptin may affect metabolism is by modifying hypothalamic astrocyte morphology, which in turn could alter synaptic inputs to hypothalamic neurons. Furthermore, the responses to acute and chronic leptin exposure are inverse, raising the possibility that increased glial activation in response to chronic leptin exposure could be involved in central leptin resistance.

Show MeSH
Related in: MedlinePlus