Hypothalamic proopiomelanocortin (POMC) neurons have a cholinergic phenotype

Eur J Neurosci. 2006 Nov;24(10):2731-40. doi: 10.1111/j.1460-9568.2006.05157.x.

Abstract

Neuronal networks originating in the hypothalamic arcuate nucleus play fundamental roles in the control of energy balance. Neuropeptide Y (NPY)-producing neurons in the arcuate nucleus stimulate food intake, whereas arcuate nucleus neurons that release the proopiomelanocortin (POMC)-derived peptide alpha-melanocyte-stimulating hormone (alpha-MSH) potently reduce food intake. Relatively little attention has been focused on classical neurotransmitters in regulation of food intake. Here, we have investigated the potential presence of acetylcholine (ACh) in NPY- and POMC-containing neuronal populations of the arcuate nucleus. Antisera to proteins required for cholinergic neurotransmission, including choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (VAChT), were employed in double-labeling immunohistochemical experiments. In colchicine-treated rats, ChAT- and VAChT-immunopositive cell bodies were located in the ventral aspect of the arcuate nucleus. ChAT and VAChT immunoreactivities were demonstrated in alpha-MSH- and cocaine- and amphetamine-regulated transcript (CART)-containing cell bodies of the arcuate nucleus, whereas cell bodies containing NPY or agouti-related peptide (AGRP) were distinct from VAChT-immunoreactive neuronal perikarya. VAChT immunoreactivity was also present in a large number of alpha-MSH-containing nerve fiber varicosities throughout the central nervous system. In the commissural part of the nucleus tractus solitarius, no alpha-MSH-containing cell bodies were found to have ChAT or VAChT immunoreactivity. The presence of markers for cholinergic neurotransmission in a subpopulation of hypothalamic POMC/CART neurons suggests co-release of ACh with peptides derived from the POMC precursor and CART. The results indicate a role for ACh in control of energy balance, mediating the effects of peripheral hormones such as leptin and insulin.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism*
  • Animals
  • Choline O-Acetyltransferase / metabolism
  • Hypothalamus / cytology*
  • Immunohistochemistry / methods
  • In Situ Hybridization / methods
  • Male
  • Microscopy, Confocal / methods
  • Nerve Tissue Proteins / metabolism
  • Neurons / metabolism*
  • Neuropeptide Y / metabolism
  • Phenotype*
  • Pro-Opiomelanocortin / genetics
  • Pro-Opiomelanocortin / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Vesicular Acetylcholine Transport Proteins / genetics
  • Vesicular Acetylcholine Transport Proteins / metabolism

Substances

  • Nerve Tissue Proteins
  • Neuropeptide Y
  • Slc18a3 protein, rat
  • Vesicular Acetylcholine Transport Proteins
  • cocaine- and amphetamine-regulated transcript protein
  • Pro-Opiomelanocortin
  • Choline O-Acetyltransferase
  • Acetylcholine