Increased locomotor activity in mice lacking the low-density lipoprotein receptor.
While the low-density lipoprotein receptor (LDLR) is best known for its role in regulating serum cholesterol, LDLR is expressed in brain, suggesting that it may play a role in CNS function as well. Here, using mice with a null mutation in LDLR (LDLR-/-), we investigated whether the absence of LDLR affects a series of behavioral functions. We also utilized the fact that plasma cholesterol levels can be regulated in LDLR-/- mice by manipulating dietary cholesterol to investigate whether elevated plasma cholesterol might independently affect behavioral performance. LDLR-/- mice showed no major deficits in general sensory or motor function. However, LDLR-/- mice exhibited increased locomotor activity in an open field test without evidence of altered anxiety in either an open field or a light/dark emergence test. By contrast, modulating dietary cholesterol produced only isolated effects. While both C57BL/6J and LDLR-/- mice fed a high cholesterol diet showed increased anxiety in a light/dark task, and LDLR-/- mice fed a high cholesterol diet exhibited longer target latencies in the probe trial of the Morris water maze, no other findings supported a general effect of cholesterol on anxiety or spatial memory. Collectively these studies suggest that while LDLR-/- mice exhibit no major developmental defects, LDLR nevertheless plays a significant role in modulating locomotor behavior in the adult.
Elder
Gregory A
GA
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.
Ragnauth
Andre
A
Dorr
Nathan
N
Franciosi
Sonia
S
Schmeidler
James
J
Haroutunian
Vahram
V
Buxbaum
Joseph D
JD
D000161:Acoustic Stimulation; D000223:Adaptation, Psychological / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D049628:Body Size / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D005106:Exploratory Behavior / Q000502:physiology; D007266:Inhibition, Psychological; D008124:Locomotion / Q000235:genetics*; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency*; D013216:Reflex, Startle / Q000235:genetics
D011973:Receptors, LDL; D002784:Cholesterol