Antisense knockdown of drebrin A, a dendritic spine protein, causes stronger preference, impaired pre-pulse inhibition, and an increased sensitivity to psychostimulant.
Drebrin located in dendritic spines regulates their morphological changes and plays a role in the synaptic plasticity via spine function. Reduced drebrin has been found in the brain of patients with Alzheimer's disease or Down's syndrome. To examine whether the down-regulation of drebrin protein levels causes deficits in higher brain function, such as memory or cognition, we performed antisense-induced knockdown of drebrin A expression in rat brain using an hemagglutinating virus of Japan (HVJ)-liposome gene transfer technique. We investigated the effects of drebrin in vivo knockdown on spatial memory in a water-maze task, sensorimotor gating in a pre-pulse-inhibition test, adaptive behaviors in an open-field test, and sensitivity to psychostimulant in an amphetamine-induced locomotor response. Rats with drebrin A in vivo knockdown displayed a stronger preference for a previous event due to perseverative behavior, impaired pre-pulse inhibition (PPI), increased locomotor activity, anxiety-like behavior, and an increased sensitivity to psychostimulant, suggesting behaviors related to schizophrenia. These findings indicated that decreased drebrin produces deficits in cognitive function but not in spatial memory, probably via hypofunction of dendritic spines.
Kobayashi
Rika
R
Division of Brain Science, Kitasato University Graduate School of Medical Sciences, Sagamihara 228-8555, Japan.
Sekino
Yuko
Y
Shirao
Tomoaki
T
Tanaka
Satoshi
S
Ogura
Taichi
T
Inada
Ken
K
Saji
Makoto
M
D000223:Adaptation, Psychological / Q000502:physiology; D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D022761:Gene Transfer, Horizontal; D005822:Genetic Vectors; D007276:Injections, Intraventricular / Q000379:methods; D008081:Liposomes / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000502:physiology; D029082:Sendai virus / Q000235:genetics; D013997:Time Factors
D000697:Central Nervous System Stimulants; D008081:Liposomes; D009479:Neuropeptides; D016376:Oligonucleotides, Antisense; C053386:drebrins; D000661:Amphetamine