T cell deficiency leads to cognitive dysfunction: Implications for therapeutic vaccination for schizophrenia and other psychiatric conditions

被引:373
作者
Kipnis, J [1 ]
Cohen, H
Cardon, M
Ziv, Y
Schwartz, M
机构
[1] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel
[2] Ben Gurion Univ Negev, Fac Hlth Sci, Anxiety & Stress Res Unit, Minist Hlth Mental Hlth Ctr, IL-84105 Beer Sheva, Israel
关键词
D O I
10.1073/pnas.0402268101
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 effects of the adaptive immune system on the cognitive performance and abnormal behaviors seen in mental disorders such as schizophrenia have never been documented. Here, we show that mice deprived of mature T cells manifested cognitive deficits and behavioral abnormalities, which were remediable by T cell restoration. T cell-based vaccination, using glatiramer acetate (copolymer-1, a weak agonist of numerous self-reactive T cells), can overcome the behavioral and cognitive abnormalities that accompany neurotransmitter imbalance induced by (+)dizocilpine maleate (MK-801) or amphetamine. The results, by suggesting that peripheral T cell deficit can lead to cognitive and behavioral impairment, highlight the importance of properly functioning adaptive immunity in the maintenance of mental activity and in coping with conditions leading to cognitive deficits. These findings point to critical factors likely to contribute to age- and AIDS-related dementias and might herald the development of a therapeutic vaccination for fighting off cognitive dysfunction and psychiatric conditions.
引用
收藏
页码:8180 / 8185
页数:6
相关论文
共 48 条
[1]   Glatiramer acetate-specific T cells in the brain express T helper 2/3 cytokines and brain-derived neurotrophic factor in situ [J].
Aharoni, R ;
Kayhan, B ;
Eilam, R ;
Sela, M ;
Arnon, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (24) :14157-14162
[2]   Oral treatment of mice with copolymer 1 (glatiramer acetate) results in the accumulation of specific Th2 cells in the central nervous system [J].
Aharoni, R ;
Meshorer, A ;
Sela, M ;
Arnon, R .
JOURNAL OF NEUROIMMUNOLOGY, 2002, 126 (1-2) :58-68
[3]   A behavioral analysis of the spatial learning deficit induced by the NMDA receptor antagonist MK-801 (dizocilpine) in the rat [J].
Åhlander, M ;
Misane, I ;
Schött, PA ;
Ögren, SO .
NEUROPSYCHOPHARMACOLOGY, 1999, 21 (03) :414-426
[4]  
AMITAL H, 1993, ISRAEL J MED SCI, V29, P593
[5]   Therapeutic vaccine for acute and chronic motor neuron diseases: Implications for amyotrophic lateral sclerosis [J].
Angelov, DN ;
Waibel, S ;
Guntinas-Lichius, O ;
Lenzen, M ;
Neiss, WF ;
Tomov, TL ;
Yoles, E ;
Kipnis, J ;
Schori, H ;
Reuter, A ;
Ludolph, A ;
Schwartz, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (08) :4790-4795
[6]   Antigenic specificity of immunoprotective therapeutic vaccination for glaucoma [J].
Bakalash, S ;
Kessler, A ;
Mizrahi, T ;
Nussenblatt, R ;
Schwartz, M .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2003, 44 (08) :3374-3381
[7]   Fine mapping of the schizophrenia susceptibility locus on chromosome 1q22 [J].
Brzustowicz, LM ;
Hayter, JE ;
Hodgkinson, KA ;
Chow, EWC ;
Bassett, AS .
HUMAN HEREDITY, 2002, 54 (04) :199-209
[8]  
de Kloet E Ronald, 2003, Endocr Regul, V37, P51
[9]   A revised excitotoxic hypothesis of schizophrenia: Therapeutic implications [J].
Deutsch, SI ;
Rosse, RB ;
Schwartz, BL ;
Mastropaolo, J .
CLINICAL NEUROPHARMACOLOGY, 2001, 24 (01) :43-49
[10]   Schizophrenia, III [J].
Egan, MF ;
Weinberger, DR ;
Lu, B .
AMERICAN JOURNAL OF PSYCHIATRY, 2003, 160 (07) :1242-1242