Protein kinase C overactivity impairs prefrontal cortical regulation of working memory

被引:232
作者
Birnbaum, SG
Yuan, PX
Wang, M
Vijayraghavan, S
Bloom, AK
Davis, DJ
Gobeske, KT
Sweatt, JD
Manji, HK
Arnsten, AFT
机构
[1] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06520 USA
[2] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA
[3] NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA
关键词
D O I
10.1126/science.1100021
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal cortex, as seen for example during stress exposure, markedly impair behavioral and electrophysiological measures of working memory. These data suggest that excessive PKC activation can disrupt prefrontal cortical regulation of behavior and thought, possibly contributing to signs of prefrontal cortical dysfunction such as distractibility, impaired judgment, impulsivity, and thought disorder.
引用
收藏
页码:882 / 884
页数:3
相关论文
共 18 条
[1]   α-1 noradrenergic receptor stimulation impairs prefrontal cortical cognitive function [J].
Arnsten, AFT ;
Mathew, R ;
Ubriani, R ;
Taylor, JR ;
Li, BM .
BIOLOGICAL PSYCHIATRY, 1999, 45 (01) :26-31
[2]   Research: Neuroscience - The biology of being frazzled [J].
Arnsten, AFT .
SCIENCE, 1998, 280 (5370) :1711-1712
[3]   The alpha-1 adrenergic agonist, cirazoline, impairs spatial working memory performance in aged monkeys [J].
Arnsten, AFT ;
Jentsch, JD .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1997, 58 (01) :55-59
[4]   A role for norepinephrine in stress-induced cognitive deficits:: α-1-adrenoceptor mediation in the prefrontal cortex [J].
Birnbaum, S ;
Gobeske, KT ;
Auerbach, J ;
Taylor, JR ;
Arnsten, AFT .
BIOLOGICAL PSYCHIATRY, 1999, 46 (09) :1266-1274
[5]  
Blumberg HP, 1999, AM J PSYCHIAT, V156, P1986
[6]   Getting balance: Drugs for bipolar disorder share target [J].
Coyle, JT ;
Manji, HK .
NATURE MEDICINE, 2002, 8 (06) :557-558
[7]  
ELLICOTT A, 1990, AM J PSYCHIAT, V147, P1194
[8]   The role of the prefrontal cortex in self-consciousness: The case of auditory hallucinations [J].
Frith, C .
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 1996, 351 (1346) :1505-1512
[9]  
GOLDMANRAKIC PS, 1991, AM PSYCHOP, P1
[10]   Up-regulation of the D1 dopamine receptor-interacting protein, calcyon, in patients with schizophrenia [J].
Koh, PO ;
Bergson, C ;
Undie, AS ;
Goldman-Rakic, PS ;
Lidow, MS .
ARCHIVES OF GENERAL PSYCHIATRY, 2003, 60 (03) :311-319