Gene/Protein Disease Symptom Drug Enzyme Compound
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Narcolepsy is a disabling sleep disorder of unknown aetiology. In humans, the disease is mostly sporadic, with a few familial cases having been reported. In 1973 a sporadic case of narcolepsy was reported in a poodle, and in 1975 familial cases of narcolepsy occurred in dobermanns. As with human narcoleptics, these narcoleptic dogs exhibited excessive daytime sleepiness and cataplexy. A colony of narcoleptic dogs was established at Stanford University in 1976 to study the pathophysiology of the disease. Between 1976 and 1995, a total of 669 animals of various breeds were born, of which 487 survived. Dobermanns accounted for 78 per cent of the total. The narcolepsy genotype in dobermanns had no significant influence on puppy mortality rate (numbers of stillborn and survival rate). The sex, maternal parity or the age of the sire or dam had no significant effect. The percentage of stillborn puppies increased from 6.1 per cent in outbred litters to 15.4 per cent in inbred litters (P = 0.10). Birth season also had a significant effect, and the highest survival rate (P = 0.02), and the lowest percentage of stillborn puppies (P = 0.09) occurred between April and June.
Vet Rec 1998 Jan 10
PMID:Breeding history of the Stanford colony of narcoleptic dogs. 948 25

A two-year-old male chihuahua suffered attacks of muscle weakness and immobility, although it had no family history of paroxysmal attacks. No neurological or blood biochemical abnormalities were recorded when it was first examined. The attacks were typically elicited by stimulation, such as feeding, and a case of sporadic narcolepsy-cataplexy was therefore suspected. Treatment orally three times a day with 1 mg/kg imipramine, was effective in reducing the attacks. The concentration of hypocretin-1/orexin A in the dog's cerebrospinal fluid was less than 80 pg/ml (22.5 pmol/litre), compared with normal canine levels of 250 to 350 pg/ml (70.0 to 98.3 pmol/litre), supporting a diagnosis of hypocretin-deficient narcolepsy.
Vet Rec 2003 Jun 21
PMID:Narcolepsy in a hypocretin/orexin-deficient chihuahua. 1284 89

Narcolepsy is a chronic sleep disorder that affects human beings and animals. Up to 17 breeds of dogs are affected sporadically, and familial forms occur in dobermanns, labrador retrievers and dachshunds. These dogs display characteristics strikingly similar to those of human narcolepsy, including cataplexy (a sudden loss of muscle tone in response to emotional stimulation) and a shorter sleep latency. It has recently been shown that the aetiology of both the familial form (receptor null mutation) and the sporadic form (loss of ligand production) of canine narcolepsy is associated with a deficit in hypocretin/orexin neurotransmission. Hypocretin deficiency can be detected by the measurement of hypocretin-1 in cerebrospinal fluid, and this could be used to diagnose hypocretin ligand deficient cases in clinical practice. Narcolepsy is neither progressive nor life-threatening, but the clinical signs persist throughout life, and lifelong treatment and care are required. This article reviews the recent progress in narcolepsy research in dogs, and describes the diagnosis and treatment of the disease.
Vet Rec 2007 Sep 15
PMID:Review of pathophysiology and clinical management of narcolepsy in dogs. 1787 67

The cat ventral oral pontine reticular nucleus (vRPO) is responsible for the generation and maintenance of rapid eye movement (REM) sleep. Hypothalamic neurons containing the peptide hypocretin-1 (also called orexin-A) which will be herewith defined as orexinergic (Orx) neurons, occupy a pre-eminent place in the integration and stabilization of arousal networks as well as in the physiopathology of narcolepsy/cataplexy. In the previous investigations, low-volume and dose microinjections of hypocretin-1 in cat vRPO produced a specific and significant suppression of REM sleep. The aim of this study is to map the hypothalamic Orx neurons that project to the vRPO and suppress REM sleep generation in the cat. Five adult cats received microinjections of the retrograde tracer cholera toxin (CTb) into the vRPO. Brains were processed employing both CTb staining and antiorexin-A immunocytochemistry techniques. A large number of double-labeled neurons (Orx-CTb) intermingled with the single CTb-positive and single Orx neurons were detected in the ipsilateral lateral, perifornical, dorsal, anterior, perimammillothalamic, and posterior hypothalamic areas but were very scarce in the paraventricular, dorsomedial, ventromedial, and periventricular hypothalamic nuclei. A considerable number of double-labeled neurons were also observed in both the dorsal and the lateral hypothalamic areas in the contralateral hypothalamus. Our results suggest that the widely distributed Orx neuronal hypothalamic groups could physiologically inhibit REM sleep generation in vRPO.
Anat Rec (Hoboken) 2013 May
PMID:Hypothalamic hypocretinergic/orexinergic neurons projecting to the oral pontine rapid eye movement sleep inducing site in the cat. 2356 22