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Mice Heterozygous for Cathepsin D Deficiency Exhibit Mania-Related Behavior and Stress-Induced Depression

Mice Heterozygous for Cathepsin D Deficiency Exhibit Mania-Related Behavior and Stress-Induced Depression

Rui Zhou, Yi Lu, Yong Han, Xia Li, Huifang Lou, Liya Zhu, Xuechu Zhen, Shumin Duan

Prog Neuropsychopharmacol Biol Psychiatry. 2015 Dec 3;63:110-8.

PMID: 26092248

Abstract:

Mutations in cathepsin D (CTSD), an aspartic protease in the endosomal-lysosomal system, underlie congenital neuronal ceroid-lipofuscinosis (cNCL, also known as CLN10), a devastating neurodegenerative disease. CLN10 patients die within the first few days of life, and in the few patients who live into adulthood psychopathological symptoms have not been reported. Extensive neuropathology and altered neurotransmission have been reported in CTSD-deficient mice; however signs of neuropsychiatric behavior in these mice are not well characterized due to the severe movement disorder and premature death of the animal. In the present study, we show that heterozygous CTSD-deficient (CTSD HET) mice display an overall behavioral profile that is similar to human mania, including hyperlocomotion, d-amphetamine-induced hyperactivity, sleep-disturbance, and reduced anxiety-like behavior. However, under stressful conditions CTSD HET mice manifest depressive-like behavior, including anhedonia, behavioral despair, and enhanced learned helplessness. Chronic administration of lithium chloride or valproic acid, two clinically effective mood stabilizers, reverses the majority of these behavioral abnormalities. In addition, CTSD HET mice display stress-induced hypersecretion of corticosterone. These findings suggest an important role for CTSD in the regulation of mood stabilization.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP62391995	Valproic Acid Related Compound B		62391-99-5	Price

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