Endocannabinoids and CB1 receptors stimulate food deprivation by acting on hypothalamic neurons. We have focused our study on the endocannabinoid/orexin-1 interactions in ob/ob mice and littermates in order to investigate, in obesity, the inhibitory role of cannabinoids on orexinergic neurons as yet suggested in physiological conditions. The immunodetection of orexin-1 (OX-1), CB1, DAGL-α and NAPE-PLD (the endocannabinoid biosynthesising enzymes) and vescicular GABA or glutamate transporters as markers of GABAergic or glutamatergic fibers was performed in single and double immunostaining by immunoperoxidase, immunofluorescence and immunogold techniques. The immunoperoxidase staining was followed by quantitative analysis of each immunoreactive signal using a digital densitometric system. Lateral hypothalamus orexinergic neurons exhibited DAGL-α immunoreactivity (IR) in the somatodendritic compartment and were immersed in a meshwork of CB1-positive fibers. Increased DAGL-α , but not NAPE-PLD, was observed both in the LH and arcuate nucleus of obese vs. lean mice. CB1-IR was localized on both glutamatergic and GABAergic axon terminals surrounding orexinergic neurons. A significant increase of 2-AG, but not of AEA, levels was also found in the hypothalamus of obese vs. lean mice. These results suggest a model of retrograde control by CB1 over OX-1 release. In obese mice, the increase of DAGL-α and 2-AG in orexinergic neurons might cause a postsynaptic disinhibition of orexin release by 2-AG acting on presynaptic CB1-expressing GABAergic neurons and contribute to hyperphagia.

Immunocytochemical study on the endocannabinoid and Orexin-1 interactions in the hypothalamus / Ferrandino, Ida; R., Imperatore; R., Favorito; V., Di Marzo; L., Cristino. - In: EUROPEAN JOURNAL OF HISTOCHEMISTRY. - ISSN 1121-760X. - STAMPA. - 53:(2009), pp. 21-21.

Immunocytochemical study on the endocannabinoid and Orexin-1 interactions in the hypothalamus.

FERRANDINO, IDA;
2009

Abstract

Endocannabinoids and CB1 receptors stimulate food deprivation by acting on hypothalamic neurons. We have focused our study on the endocannabinoid/orexin-1 interactions in ob/ob mice and littermates in order to investigate, in obesity, the inhibitory role of cannabinoids on orexinergic neurons as yet suggested in physiological conditions. The immunodetection of orexin-1 (OX-1), CB1, DAGL-α and NAPE-PLD (the endocannabinoid biosynthesising enzymes) and vescicular GABA or glutamate transporters as markers of GABAergic or glutamatergic fibers was performed in single and double immunostaining by immunoperoxidase, immunofluorescence and immunogold techniques. The immunoperoxidase staining was followed by quantitative analysis of each immunoreactive signal using a digital densitometric system. Lateral hypothalamus orexinergic neurons exhibited DAGL-α immunoreactivity (IR) in the somatodendritic compartment and were immersed in a meshwork of CB1-positive fibers. Increased DAGL-α , but not NAPE-PLD, was observed both in the LH and arcuate nucleus of obese vs. lean mice. CB1-IR was localized on both glutamatergic and GABAergic axon terminals surrounding orexinergic neurons. A significant increase of 2-AG, but not of AEA, levels was also found in the hypothalamus of obese vs. lean mice. These results suggest a model of retrograde control by CB1 over OX-1 release. In obese mice, the increase of DAGL-α and 2-AG in orexinergic neurons might cause a postsynaptic disinhibition of orexin release by 2-AG acting on presynaptic CB1-expressing GABAergic neurons and contribute to hyperphagia.
2009
Immunocytochemical study on the endocannabinoid and Orexin-1 interactions in the hypothalamus / Ferrandino, Ida; R., Imperatore; R., Favorito; V., Di Marzo; L., Cristino. - In: EUROPEAN JOURNAL OF HISTOCHEMISTRY. - ISSN 1121-760X. - STAMPA. - 53:(2009), pp. 21-21.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/356365
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