Effects of hypocretin-1 in 192-IgG-saporin-lesioned rats.

Full Abstract

Hypocretin, also known as orexin, is a neuropeptide located in the perifornical region of the lateral hypothalamus; this region projects to all the major arousal centres including the basal forebrain. The basal forebrain contains a mixed population of neurons, some of which are cholinergic. To identify the relative contribution of the noncholinergic neurons to arousal, here we utilized 192-IgG-saporin to lesion the basal forebrain cholinergic neurons and determine whether microinjection of hypocretin-1 to the basal forebrain is still effective in inducing arousal. In Sprague-Dawley rats given 192-IgG-saporin (intraventricular, 6 microg; n=7) 92% of the basal forebrain cholinergic neurons were destroyed compared to nonlesioned rats (n=5). In the lesioned rats microinjection of hypocretin-1 (0.0625, 0.125 or 0.25 nmol in 250 nL) to the basal forebrain increased waking and suppressed sleep (both non-REM and REM) in a concentration-dependent manner and to the same extent as in nonlesioned rats. These results suggest that, in the absence of the basal forebrain cholinergic neurons, the basal forebrain noncholinergic neurons are able to convey hypocretin's arousal signal unabated.

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Author information

Author/s: Blanco-Centurion, Carlos A (CA); Shiromani, Anjelica (A); Winston, Elizabeth (E); Shiromani, Priyattam J (PJ);

Affiliation: Department of Neurology, West Roxbury VA Medical Center and Harvard Medical School, 1400 VFW Parkway, West Roxbury, MA 02132, USA.

Grants: MH55772 (Agency:NIMH NIH HHS) ; NS052287 (Agency:NINDS NIH HHS) ; NS30140 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.

Journal: The European journal of neuroscience (Eur J Neurosci), published in France. (Language: eng)

Reference: 2006-Oct; vol 24 (issue 7) : pp 2084-8

Dates: Created 2006/10/27; Completed 2006/12/21; Revised 2007/11/15;

PMID: 17067305, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Analysis of Variance
Animals
Antibodies, Monoclonal
Brain Injuries - chemically induced; metabolism; physiopathology
Choline O-Acetyltransferase - metabolism
Dose-Response Relationship, Drug
Immunohistochemistry - methods
Immunotoxins
Intracellular Signaling Peptides and Proteins - metabolism; pharmacology

Male
N-Glycosyl Hydrolases
Neuropeptides - metabolism; pharmacology
Rats
Rats, Sprague-Dawley
Reaction Time - drug effects; physiology
Ribosome Inactivating Proteins, Type 1
Sleep - drug effects; physiology
Walking - physiology

Associated Chemicals: 192 IgG-saporin (0) ; Antibodies, Monoclonal (0) ; Immunotoxins (0) ; Intracellular Signaling Peptides and Proteins (0) ; Neuropeptides (0) ; Ribosome Inactivating Proteins, Type 1 (0) ; orexins (0) ; Choline O-Acetyltransferase (EC 2.3.1.6) ; N-Glycosyl Hydrolases (EC 3.2.2.-)

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