In the rat brain there are about 1100-4000 (depending of the authors) immunoreactive cell bodies for hypocretins.34 These neurons are mainly localized in the tuberal region of the hypothalamus within the perifornical and dorsomedial hypothalamic (DMN) nuclei and the dorsal and lateral (LHA) hypothalamic areas in rat,6'7'35-39 mouse,35'40'41 hamster,42-44 guinea pig,45 the rodent Arvicanthis niloticus,46 cat,47-49 sheep,50 monkey,3951 human,52-54 frog55 and Xenopus.56
In contrast with the restricted localization of hypocretin cell bodies, hypocretin fibres are widely distributed throughout the brain and all levels of the spinal cord.35-4057 In the hypothalamus, hypocretin projections are found in the preoptic (PO), suprachiasmatic (SPN), supraoptic (SON), tuberomamillary, dorsomedial (DMN), paraventricular (PVN), periventricular (PeN), ventromedial (VMN) and arcuate (ARC) nuclei35,36,38,39,57 all of them with major roles in the control of the different endocrine axes.
Hypocretin receptors (Hcrtrs) show widespread distribution in the rat brain and spinal cord and their pattern of expression is consistent with the map of hypocretin containing projections. In the rat hypothalamus neurons expressing hypocretin receptor 1 (Hcrtr1) were observed in the preoptic, suprachiasmatic, periventricular, paraventricular (magno- and parvocellular divisions), supraoptic, arcuate, ventromedial, dorsomedial and tuberomamillary nuclei and the lateral hypothalamic area.58-61 In the rat, in all these hypothalamic nuclei Hcrtr1 co-localizes with another neuropeptide systems implicated in endocrine control. Thus, in magnocellular neurons of the paraventricular and supraoptic nuclei Hcrtr1 immunoreactivity is localized in arginine vasopressin (ADH) and oxytocin (OT) expressing neurons. Moreover, Hcrtr1 is present in vasopressin and vasoactive intestinal polypeptide (VIP) neurons in the suprachiasmatic nucleus, in somatostatin (SST) neurons in the periventricular nucleus, and in corticotropin-releasing hormone (CRH) neurons in the parvocellular part of the paraventricular nucleus.61 In the arcuate nucleus, Hcrtr1 is detected in neuropeptide Y (NPY) neurons of the ventromedial part and in proopiomelanocortin (POMC) neurons of the ventrolateral part.61 Moreover, Hcrtr1 is expressed in the septal and medial preoptic area of the rat brain586062 on LHRH neurons.63 These results suggest that Hcrtr1 signalling may play a role in the control of several endocrine systems such as the adrenal, the somatotrope and the reproductive axes.14,58,60,62
The central expression pattern of hypocretin receptor 2 (Hcrtr2) has been extensively studied in the rat 58-60 64 Therefore, in the rat hypothalamus, Hcrtr2 mRNA has been predominantly found in the medial parvocellular part of the paraventricular nucleus, in the arcuate nucleus, in the premammillary and tuberomamillary nuclei and in the lateral hypothalamic area. Moderate Hcrtr2 mRNA content is detected in the ventromedial, dorsomedial, periventricular hypothalamic nuclei and in the posterior and preoptic hypothalamic areas. Hcrtr2 mRNA levels are low in the supraoptic nucleus and in the dorsal and lateral parts of the paraventricular nucleus. No Hcrtr2 mRNA has been detected in the magnocellular neurons of the paraventricular nucleus.58-60 So far, only one study has described in detail Hcrtr2 protein distribution in the rat hypothalamus.64 However, there are no available results about the co-expression of this receptor with other neuropeptide systems implicated in endocrine regulation.
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