TY - JOUR
T1 - Orexin/hypocretin and histamine
T2 - Distinct roles in the control of wakefulness demonstrated using knock-out mouse models
AU - Anaclet, Christelle
AU - Parmentier, Régis
AU - Ouk, Koliane
AU - Guidon, Gérard
AU - Buda, Colette
AU - Sastre, Jean Pierre
AU - Akaoka, Hidéo
AU - Sergeeva, Olga A.
AU - Yanagisawa, Masashi
AU - Ohtsu, Hiroshi
AU - Franco, Patricia
AU - Haas, Helmut L.
AU - Lin, Jian Sheng
PY - 2009/11/18
Y1 - 2009/11/18
N2 - To determine the respective role played by orexin/hypocretin and histamine (HA) neurons in maintaining wakefulness (W), we characterized the behavioral and sleep-wake phenotypes of orexin (Ox) knock-out (-/-) mice and compared them with those of histidine-decarboxylase (HDC, HA-synthesizing enzyme)-/- mice. While both mouse strains displayed sleep fragmentation and increased paradoxical sleep (PS), they presented a number of marked differences: (1) the PS increase in HDC-/- mice was seen during lightness, whereas that in Ox-/-mice occurred during darkness; (2) contrary to HDC-/-, Ox-/-mice had no W deficiency around lights-off, nor an abnormal EEG and responded to a new environment with increased W; (3) only Ox-/-, but not HDC-/-mice, displayed narcolepsy and deficient W when faced with motor challenge. Thus, when placed on a wheel, wild-type (WT), but not littermate Ox-/- mice, voluntarily spent their time in turning it and as a result, remained highly awake; this was accompanied by dense c-fos expression in many areas of their brains, including Ox neurons in the dorsolateral hypothalamus. The W and motor deficiency of Ox-/- mice was due to the absence of Ox because intraventricular dosing of orexin-A restored their W amount and motor performance whereas SB-334867 (Ox1-receptor antagonist, i.p.) impaired Wand locomotion of WT mice during the test. These data indicate that Ox, but not HA, promotes W through enhanced locomotion and suggest that HA and Ox neurons exert a distinct, but complementary and synergistic control of W: the neuropeptide being more involved in its behavioral aspects, whereas the amine is mainly responsible for its qualitative cognitive aspects and cortical EEG activation.
AB - To determine the respective role played by orexin/hypocretin and histamine (HA) neurons in maintaining wakefulness (W), we characterized the behavioral and sleep-wake phenotypes of orexin (Ox) knock-out (-/-) mice and compared them with those of histidine-decarboxylase (HDC, HA-synthesizing enzyme)-/- mice. While both mouse strains displayed sleep fragmentation and increased paradoxical sleep (PS), they presented a number of marked differences: (1) the PS increase in HDC-/- mice was seen during lightness, whereas that in Ox-/-mice occurred during darkness; (2) contrary to HDC-/-, Ox-/-mice had no W deficiency around lights-off, nor an abnormal EEG and responded to a new environment with increased W; (3) only Ox-/-, but not HDC-/-mice, displayed narcolepsy and deficient W when faced with motor challenge. Thus, when placed on a wheel, wild-type (WT), but not littermate Ox-/- mice, voluntarily spent their time in turning it and as a result, remained highly awake; this was accompanied by dense c-fos expression in many areas of their brains, including Ox neurons in the dorsolateral hypothalamus. The W and motor deficiency of Ox-/- mice was due to the absence of Ox because intraventricular dosing of orexin-A restored their W amount and motor performance whereas SB-334867 (Ox1-receptor antagonist, i.p.) impaired Wand locomotion of WT mice during the test. These data indicate that Ox, but not HA, promotes W through enhanced locomotion and suggest that HA and Ox neurons exert a distinct, but complementary and synergistic control of W: the neuropeptide being more involved in its behavioral aspects, whereas the amine is mainly responsible for its qualitative cognitive aspects and cortical EEG activation.
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U2 - 10.1523/JNEUROSCI.2604-09.2009
DO - 10.1523/JNEUROSCI.2604-09.2009
M3 - Article
C2 - 19923277
AN - SCOPUS:70949083914
SN - 0270-6474
VL - 29
SP - 14423
EP - 14438
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 46
ER -