Orexin (hypocretin) neurons contain dynorphin.

T. C. Chou, C. E. Lee, J. Lu, J. K. Elmquist, J. Hara, J. T. Willie, C. T. Beuckmann, R. M. Chemelli, T. Sakurai, M. Yanagisawa, C. B. Saper, T. E. Scammell

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Abstract

Orexins (also called hypocretins) are peptide neurotransmitters expressed in neurons of the lateral hypothalamic area (LHA). Mice lacking the orexin peptides develop narcolepsy-like symptoms, whereas mice with a selective loss of the orexin neurons develop hypophagia and severe obesity in addition to the narcolepsy phenotype. These different phenotypes suggest that orexin neurons may contain neurotransmitters besides orexin that regulate feeding and energy balance. Dynorphin neurons are common in the LHA, and dynorphin has been shown to influence feeding; hence, we studied whether dynorphin and orexin are colocalized. In rats, double-label in situ hybridization revealed that nearly all (94%) neurons expressing prepro-orexin mRNA also expressed prodynorphin mRNA. The converse was also true: 96% of neurons in the LHA containing prodynorphin mRNA also expressed prepro-orexin mRNA. Double-label immunohistochemistry confirmed that orexin-A and dynorphin-A peptides were highly colocalized in the LHA. Wild-type mice and orexin knock-out mice showed abundant prodynorphin mRNA-expressing neurons in the LHA, but orexin/ataxin-3 mice with a selective loss of the orexin neurons completely lacked prodynorphin mRNA in this area, further confirming that within the LHA, dynorphin expression is restricted to the orexin neurons. These findings suggest that dynorphin-A may play an important role in the function of the orexin neurons.

Original languageEnglish (US)
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume21
Issue number19
StatePublished - 2001

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Dynorphins
Lateral Hypothalamic Area
Neurons
Messenger RNA
Narcolepsy
Peptides
Neurotransmitter Agents
Orexins
Phenotype
Morbid Obesity
Knockout Mice
In Situ Hybridization
Immunohistochemistry

Cite this

Chou, T. C., Lee, C. E., Lu, J., Elmquist, J. K., Hara, J., Willie, J. T., ... Scammell, T. E. (2001). Orexin (hypocretin) neurons contain dynorphin. The Journal of neuroscience : the official journal of the Society for Neuroscience, 21(19).

Orexin (hypocretin) neurons contain dynorphin. / Chou, T. C.; Lee, C. E.; Lu, J.; Elmquist, J. K.; Hara, J.; Willie, J. T.; Beuckmann, C. T.; Chemelli, R. M.; Sakurai, T.; Yanagisawa, M.; Saper, C. B.; Scammell, T. E.

In: The Journal of neuroscience : the official journal of the Society for Neuroscience, Vol. 21, No. 19, 2001.

Research output: Contribution to journalArticle

Chou, TC, Lee, CE, Lu, J, Elmquist, JK, Hara, J, Willie, JT, Beuckmann, CT, Chemelli, RM, Sakurai, T, Yanagisawa, M, Saper, CB & Scammell, TE 2001, 'Orexin (hypocretin) neurons contain dynorphin.', The Journal of neuroscience : the official journal of the Society for Neuroscience, vol. 21, no. 19.
Chou, T. C. ; Lee, C. E. ; Lu, J. ; Elmquist, J. K. ; Hara, J. ; Willie, J. T. ; Beuckmann, C. T. ; Chemelli, R. M. ; Sakurai, T. ; Yanagisawa, M. ; Saper, C. B. ; Scammell, T. E. / Orexin (hypocretin) neurons contain dynorphin. In: The Journal of neuroscience : the official journal of the Society for Neuroscience. 2001 ; Vol. 21, No. 19.
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AU - Lee, C. E.

AU - Lu, J.

AU - Elmquist, J. K.

AU - Hara, J.

AU - Willie, J. T.

AU - Beuckmann, C. T.

AU - Chemelli, R. M.

AU - Sakurai, T.

AU - Yanagisawa, M.

AU - Saper, C. B.

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