Altered emotionality, spatial memory and cholinergic function in caveolin-1 knock-out mice.
Neurological phenotypes associated with loss of caveolin 1 (cav-1) (the defining structural protein in caveolar vesicles, which regulate signal transduction and cholesterol trafficking in cells) in mice have been reported recently. In brain, cav-1 is highly expressed in neurons and glia. We investigated emotional and cognitive behavioural domains in mice deficient in cav-1 (CavKO mice). CavKO mice were more anxious and spent more time in self-directed grooming behaviour than wild-type (wt) mice. In a spatial/working memory task, CavKO mice failed to recognize the object displacement, thus showing a spatial memory impairment. CavKO mice showed higher locomotor activity than wt mice, thus suggesting reduced inhibitory function by CNS cholinergic systems. Behavioural response to the cholinergic muscarinic antagonist, scopolamine (2 mg/Kg), was decreased in CavKO mice. Few behavioural sex differences emerged in mice; whereas the sex differences were generally attenuated or even reverted in the null genotype. Our data confirm a distinct behavioural phenotype in CavKO mice and indicate a selective alteration in central cholinergic function.
Gioiosa
Laura
L
Department Cell Biology and Neuroscience, Sect of Behavioural Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, Roma, Italy.
Raggi
Carla
C
Ricceri
Laura
L
Jasmin
Jean-François
JF
Frank
Philippe G
PG
Capozza
Franco
F
Lisanti
Michael P
MP
Alleva
Enrico
E
Sargiacomo
Massimo
M
Laviola
Giovanni
G
D000109:Acetylcholine / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D051242:Caveolin 1 / Q000172:deficiency*; D002540:Cerebral Cortex / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004644:Emotions / Q000502:physiology*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D008297:Male; D008569:Memory Disorders / Q000235:genetics*; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018727:Muscarinic Antagonists / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology; D012737:Sex Factors
D051242:Caveolin 1; D018727:Muscarinic Antagonists; D012601:Scopolamine; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine