Arcuate nucleus

Two distinct populations of neurons in the arcuate nucleus have been identified as the most relevant target cells of leptin (Fig. 1, [2, 4]). Leptin inhibits expression... 

Lesions of the lateral hypothalamic area (LHA) cause anorexia, whereas ablation of the paraventricular nucleus (PVN) cause a hyperphagic obesity syndrome. Consistent with these results, LHA neurons express the orexigenic neuropeptides MCH and orexin. PVN neurons produce several neuropeptides that are anorex-igenic when administered directly into the brain (CRH, TRH, oxytocin), in addition to their better known roles as endocrine regulators. LHA and PVN receive rich inputs from axons of NPY/AgRP and aMSH/CART-producing neurons in the arcuate nucleus. 

CART (cocaine- and amphetamine-regulated transcript) is a hypothalamic peptide that inhibits both normal and starvation-induced feeding when injected into cerebral ventricles of rats. CART is co-localized with the anorexigenic peptide a-melanocyte-stimulating hormone in neurons of the arcuate nucleus. Secretion of CART is stimulated by leptin and CART may be an endogenous inhibitor of food intake. 

Fig. 8.1 (continued) nucleus, (k, 1) Hi hippocampus, (m, n) So supraoptic nucleus, (o, p) Arc hypothalamic arcuate nucleus, (q, r) PH posterior hypothalamic area, (s, t) SN Substantia nigra. AU sections were observed with an Olympus fluorescent microscope (BX 61). Scale bars = 50 mm. (Unpubhshed data)... 

A further totally separate DA pathway arises from A12 in the arcuate nucleus and forms the tuberoinfundibular tract in the median eminence to the pituitary gland for controlling prolactin release. This is partly achieved by DA being released into capillaries of the hypothalamic-hypophyseal portal system and then inhibiting the prolactin releasing cells (lactotrophs) of the anterior pituitary. 

Control (inhibition) of prolactin release Tuberoinfundibular tract from A12 in the arcuate nucleus of the median eminence to pituitary Humans Hypoprolactaemia Humans Hyperprolactaemia Galactorrhoea Amenorrhoea D2 ... 

Rosier, O. Joh, T.H. and Beaudet, A. Ultrastmctural relationships between serotonin and dopamine neurons in the rat arcuate nucleus and medial zona incerta A combined radioautographic and immunocytochemical study. Neurosci Lett 48 279-285, 1984. 

FIGURE 14-2 The histaminergic system of the rat brain. (A) Frontal sections through the posterior hypothalamus showing the location of histaminergic neurons. Arc, arcuate nucleus DM, dorsomedial nucleus LM, lateral mammillary nucleus MM, medial mammillary nucleus MR, mammillary recess PM, premammillary nucleus 3V, third ventricle VMH, ventromedial hypothalamic nucleus. (Modified with permission from reference [5].)... 

Neuropeptide Y (NPY) and its receptors may also be important in the regulation of anxiety and stress. NPY is synthesized in the arcuate nucleus, which receives LC input. In a number of rodent models, NPY administration has anxiolytic and, at somewhat higher doses, sedative effects. Likewise, NPY antagonizes CRH-induced stress responses, and suppresses LC firing when injected... 

The leptin receptor is expressed primarily in regions of the brain known to regulate feeding behavior— neurons of the arcuate nucleus of the hypothalamus... 

The anorexigenic (appetite-suppressing) neurons in the arcuate nucleus produce a-melanocyte-stimulating hormone (a-MSH), formed from its polypeptide precursor pro-opiomelanocortin (POMC Fig. 23-6). Release of a-MSH causes the next neuron in the circuit to send the signal to the brain, Stop eating ... 

Insulin Acts in the Arcuate Nucleus to Regulate Eating and Energy Conservation... 

The signal-transduction mechanism for leptin involves phosphorylation of the JAK-STAT system. On phosphorylation by JAK, STATs can bind to regulatory regions in nuclear DNA and alter the expression of genes for the proteins that set the level of metabolic activity and determine feeding behavior. Insulin acts on receptors in the arcuate nucleus, with results similar to those caused by leptin. 

Ghrelin, a hormone produced in the stomach, acts on orexigenic neurons in the arcuate nucleus to produce hunger before a meal. PYY3 35, a peptide hormone of the intestine, acts at the same site to lessen hunger after... 

Recent results from our laboratory establish CaMKKp as a physiologically relevant AMPK in mice and suggest that it mediates the ghrelin-induced activation of AMPK and NPY in hypothalamic NPY neurons. In situ hybridization revealed that CaMKKp mRNA is expressed in the arcuate nucleus of the hypothalamus. Mice null for the CaMKKp gene show decreased hypothalamic AMPK phosphorylation and activity as well as NPY/AgRP mRNAs. The CaMKKp null mice fed... 

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