Hypothalamic cocaine- and amphetamine-regulated transcript (CART) neurons: histochemical relationship to thyrotropin-releasing hormone, melanin-concentrating hormone, orexin/hypocretin and neuropeptide Y

Dec 29, 1999Brain research

Chemical relationships between specific hypothalamus neurons and hormones controlling thyroid, appetite, and wakefulness

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Abstract

CART peptides are significantly co-expressed with TRH in hypothalamic neurons.

CART peptides show a high degree of overlap with thyrotropin-releasing hormone (TRH) in the paraventricular nucleus of the hypothalamus.
Melanin-concentrating hormone (MCH) mRNA co-localizes with CART in neurons of the dorsomedial hypothalamic nucleus/lateral hypothalamic area, while orexin/hypocretin does not.
CART peptide-immunoreactive cell bodies in the arcuate nucleus and medial posterodorsal nucleus of the amygdala are closely associated with neuropeptide Y (NPY) nerve terminals.
Treatment with monosodium glutamate, a neurotoxin, resulted in a near-total loss of CART peptide-immunoreactive cell bodies in the arcuate nucleus and reduced CART peptide staining in several hypothalamic regions.
These observations suggest that hypothalamic CART neurons are integrated within the brain circuitry that regulates energy balance.

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Recent demonstrations of the feeding-inhibitory properties of putative peptides derived from cocaine- and amphetamine-regulated transcript (CART) raise the question of interactions between CART peptides and other messenger molecules implicated in the control of food intake. The present study investigated the histochemical relationship of CART to the neuropeptides thyrotropin-releasing hormone (TRH), melanin-concentrating hormone (MCH), orexin/hypocretin and neuropeptide Y (NPY) in the hypothalamus. Double-label in situ hybridization showed that CART to a great extent is co-expressed with TRH in hypothalamic paraventricular nucleus neurons. This technique was also used to demonstrate that MCH, but not orexin/hypocretin, mRNA colocalized with CART in neurons of the dorsomedial hypothalamic nucleus/lateral hypothalamic area. CART-peptide immunoreactive cell bodies in this region, as well as in the arcuate nucleus and the medial posterodorsal nucleus of the amygdala, were all seen to have close appositions formed by NPY-immunoreactive nerve terminals. Lastly, in a study of mice treated with the neurotoxin, monosodium glutamate, which targets the arcuate nucleus, a near-total ablation of CART peptide immunoreactive cell bodies in this nucleus was accompanied by decreased terminal staining for CART peptide in the paraventricular hypothalamic nucleus, the arcuate nucleus itself and in the dorsomedial hypothalamic nucleus. These findings further define the position of hypothalamic CART neurons within the hierarchy of brain circuitries regulating energy balance, demonstrating the presence of CART peptide in several cell populations that form putative down-stream targets of NPY terminals, including hypophysiotropic TRH neurons and lateral hypothalamic MCH neurons.

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Hypothalamic cocaine- and amphetamine-regulated transcript (CART) neurons: histochemical relationship to thyrotropin-releasing hormone, melanin-concentrating hormone, orexin/hypocretin and neuropeptide Y

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