Original contributionEffects of lateral hypothalamic lesion with the neurotoxin hypocretin-2–saporin on sleep in Long–Evans rats
Section snippets
Animals and surgical preparation
The studies were conducted in accordance with the principles and procedures described in the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Twenty-three male Long–Evans rats (400–550 g) were housed singly in Plexiglas cages with wood shavings, and with food and water available ad libitum. The rats were housed in a room where the temperature (21°C) and the lights were controlled (7:00 a.m. to 7:00 p.m. lights on; 100 lux). The rats were implanted under anesthesia
Neuronal loss
Fig. 1 summarizes the lesioned area in rats treated with HCRT2–SAP (450 ng), HCRT2–SAP (90 ng) and SAP (450 ng). Little or no neuronal loss was apparent with the low concentration of unconjugated SAP. The higher concentration of unconjugated SAP produced a lesion but this was much smaller compared with the conjugated SAP (see Fig. 1). Loss of HCRT neurons and NeuN-positive neurons in the DMH, VMH, and perifornical area was assessed quantitatively. The HCRT neurons located laterally were
Discussion
Human narcolepsy has been linked to a loss of HCRT neurons Peyron et al., 2000, Thannickal et al., 2000 but it is not known to what extent loss of other neurons in the LH and surrounding posterior hypothalamus contribute to the disease and the variation in symptoms. The currently available models of narcolepsy cannot adequately answer this question, since in the murine model Chemelli et al., 1999, Hara et al., 2001, only the HCRT neurons are affected, whereas in the canine model, the disease is
Acknowledgements
We thank Jill Winston for expert technical assistance and Elizabeth Winston and Samara Shiromani for data analysis. Supported by National Institutes of Health grants NS30140, AG09975, AG15853, and MH55772, and Medical Research Service of the Department of Veterans Affairs.
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