Stereological analysis of the hypothalamic hypocretin/orexin neurons in an animal model of depression.

Affective disorders often occur in combination with disrupted sleep-wake cycles and abnormal fluctuations in hypothalamic neurotransmitters. Hypocretin (orexin) is a hypothalamic neuropeptide linked to narcolepsy, a sleep-related disorder characterized by profound disturbances in the normal sleeping pattern and variable degrees of depression. Wistar-Kyoto (WKY) rats exhibit depressive characteristics and patterns of sleep disruption similar to that observed in depressed human patients. In this study we sought to determine whether the total number or the size of hypothalamic hypocretin neurons in WKY rats differ from their control, Wistar (WIS) rats. Immunocytochemical and stereological methods were applied to quantify hypocretin-1 containing neurons in the hypothalamus. The study revealed 18% fewer hypocretin-1 positive neurons as well as a 15% decrease in average neuronal soma size of hypocretin-1 producing cells in the hypothalamus of WKY rats compared to WIS rats. These findings support the view that reduced number or size of hypothalamic hypocretinergic neurons may underlie the disrupted sleep pattern associated with depressive characteristics in WKY rats.