Levels of trkA and BDNF mRNA, but not NGF mRNA, fluctuate across the estrous cycle and increase in response to acute hormone replacement

被引:201
作者
Gibbs, RB [1 ]
机构
[1] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA
基金
美国国家科学基金会;
关键词
Alzheimer's disease; aging; estrogen; progesterone; NGF receptor;
D O I
10.1016/S0006-8993(97)01511-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Recent studies suggest that hormone replacement therapy can help to reduce the risk and severity of Alzheimer's-related dementia in postmenopausal women. We have hypothesized that these effects are due, in part, to the ability for estrogen and progesterone to enhance hippocampal function, as well as the functional status of cholinergic projections to the hippocampus and cortex, by influencing the expression of specific neurotrophins and neurotrophin receptors. In the present study, quantitative in situ hybridization techniques were used to determine whether the levels of trkA mRNA in the basal forebrain, and nerve growth factor (NGF) mRNA and brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus, are significantly affected by physiological changes in circulating gonadal steroids. Gonadally intact animals were sacrificed at different stages of the estrous cycle and ovariectomized animals were sacrificed at different times following the administration of either estrogen or estrogen plus progesterone. In gonadally intact animals, significant fluctuations in the levels of trkA mRNA in the medial septum (MS), and BDNF mRNA in regions CA1 and CA3/4 of the hippocampus, were detected across the estrous cycle. In animals that received hormone replacement, a significant increase (30.4%) in trkA mRNA was detected in the MS of animals sacrificed 24 h following estrogen administration. Levels of trkA mRNA in the MS declined to control levels over the next 48 h; however, a single injection of progesterone administered 48 h after estradiol appeared to prevent any further decline in trkA mRNA over the next 24 h. In addition, significant increases in BDNF mRNA were detected in the dentate granule cell layer (73.4%), region CA1 (28.1%), and region CA3/4 (76.9%) of animals sacrificed 53 h after receiving estrogen and 5 h after receiving progesterone. No significant changes in trkA mRNA were detected in the nucleus basalis magnocellularis, and no significant changes in NGF mRNA were detected in the hippocampus. These data demonstrate that levels of trkA mRNA in the MS, and BDNF mRNA in the hippocampus, are affected by physiological changes in the levels of circulating gonadal steroids and are elevated in response to acute hormone replacement. The relevance of these effects to the ability for estrogen replacement to enhance cholinergic activity and hippocampal function, and thereby reduce the risk and severity of Alzheimer's-related dementia in postmenopausal women, is discussed. (C) 1998 Elsevier Science B.V.
引用
收藏
页码:259 / 268
页数:10
相关论文
共 46 条
[1]  
BOTHWELL M, 1995, ANNU REV NEUROSCI, V18, P223, DOI 10.1146/annurev.ne.18.030195.001255
[2]   REDUCED TRANSPORT OF [I-125] NERVE GROWTH-FACTOR BY CHOLINERGIC NEURONS AND DOWN-REGULATED TRKA EXPRESSION IN THE MEDIAL SEPTUM OF AGED RATS [J].
COOPER, JD ;
LINDHOLM, D ;
SOFRONIEW, MV .
NEUROSCIENCE, 1994, 62 (03) :625-629
[3]  
Courtney MJ, 1997, J NEUROSCI, V17, P4201
[4]   COEXISTENCE OF CHOLINE-ACETYLTRANSFERASE AND NERVE GROWTH-FACTOR RECEPTORS IN THE RAT BASAL FOREBRAIN [J].
DAWBARN, D ;
ALLEN, SJ ;
SEMENENKO, FM .
NEUROSCIENCE LETTERS, 1988, 94 (1-2) :138-144
[5]   CHOLINERGIC MECHANISMS IN LEARNING, MEMORY AND DEMENTIA - A REVIEW OF RECENT-EVIDENCE [J].
FIBIGER, HC .
TRENDS IN NEUROSCIENCES, 1991, 14 (06) :220-223
[6]   Effects of estrogen on potassium-stimulated acetylcholine release in the hippocampus and overlying cortex of adult rats [J].
Gibbs, RB ;
Hashash, A ;
Johnson, DA .
BRAIN RESEARCH, 1997, 749 (01) :143-146
[7]   EFFECTS OF ESTROGEN AND FIMBRIA FORNIX TRANSECTION ON P75(NGFR) AND CHAT EXPRESSION IN THE MEDIAL SEPTUM AND DIAGONAL BAND OF BROCA [J].
GIBBS, RB ;
PFAFF, DW .
EXPERIMENTAL NEUROLOGY, 1992, 116 (01) :23-39
[8]   EFFECTS OF ESTROGEN REPLACEMENT ON THE RELATIVE LEVELS OF CHOLINE-ACETYLTRANSFERASE, TRKA, AND NERVE GROWTH-FACTOR MESSENGER-RNAS IN THE BASAL FOREBRAIN AND HIPPOCAMPAL-FORMATION OF ADULT-RATS [J].
GIBBS, RB ;
WU, DH ;
HERSH, LB ;
PFAFF, DW .
EXPERIMENTAL NEUROLOGY, 1994, 129 (01) :70-80
[9]   Effects of estrogen on basal forebrain cholinergic neurons vary as a function of dose and duration of treatment [J].
Gibbs, RB .
BRAIN RESEARCH, 1997, 757 (01) :10-16
[10]  
Gibbs RB, 1996, J NEUROSCI, V16, P1049