Antisense oligodeoxynucleotide effects on the hypothalamic-neurohypophysial system and the hypothalamic-pituitary-adrenal axis

被引:3
作者
Neumann, ID [1 ]
机构
[1] Max Planck Inst Psychiat, Dept Behav Neuroendocrinol, D-80804 Munich, Germany
关键词
D O I
10.1006/meth.2000.1074
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The possibility of sequence-dependent, transient, and local inhibition of neuropeptide or neuropeptide receptor expression within the brain makes antisense targeting an attractive approach for those interested in the involvement of brain neuropeptide systems in behavioral and neuroendocrine regulation, Here, I describe our attempts to manipulate the synthetic activity of peptidergic systems of the hypothalamic-neurohypophysial system, i.e., oxytocin and vasopressin, and the hypothalamic-pituitary-adrenal (HPA) axis by antisense oligodeoxynucleotides. Detailed experimental protocols including different approaches for intracerebral antisense application in anesthetized or conscious rats are provided. As a consequence of local oxytocin or vasopressin antisense treatment within the hypothalamic supraoptic nucleus, various aspects of the neuronal activity are already altered after a few hours. Thus, we monitored electrophysiological parameters of oxytocinergic and vasopressinergic neurons, stimulus-induced expression of the Fos protein in oxytocin neurons, and stimulated release of oxytocin or vasopressin into blood as well as within the hypothalamus by dendrites and cell bodies as measured by simultaneous microdialysis in blood and brain, shortly after a single acute antisense infusion. We also employed chronic antisense infusion via osmotic minipumps or by repeated local infusion into the targeted brain region; for example, septal vasopressin receptor downregulation impairs the ability of male rats to discriminate between juvenile rats. Further, reduction of the amount of available CRH, vasopressin, and oxytocin within the hypothalamic paraventricular nuclei alters the neuroendocrine stress response of the HPA axis. (C) 2000 Academic Press.
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页码:227 / 237
页数:11
相关论文
共 40 条
[1]  
[Anonymous], **NON-TRADITIONAL**
[2]  
BOURQUE CW, 1990, FRONT NEUROENDOCRIN, V11, P183
[3]   SOCIAL DISCRIMINATION PROCEDURE - AN ALTERNATIVE METHOD TO INVESTIGATE JUVENILE RECOGNITION ABILITIES IN RATS [J].
ENGELMANN, M ;
WOTJAK, CT ;
LANDGRAF, R .
PHYSIOLOGY & BEHAVIOR, 1995, 58 (02) :315-321
[4]   Behavioral consequences of intracerebral vasopressin and oxytocin: Focus on learning and memory [J].
Engelmann, M ;
Wotjak, CT ;
Neumann, I ;
Ludwig, M ;
Landgraf, R .
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, 1996, 20 (03) :341-358
[5]   OXYTOCIN NEURON ACTIVATION AND FOS EXPRESSION - A QUANTITATIVE IMMUNOCYTOCHEMICAL ANALYSIS OF THE EFFECT OF LACTATION, PARTURITION, OSMOTIC AND CARDIOVASCULAR STIMULATION [J].
FENELON, VS ;
POULAIN, DA ;
THEODOSIS, DT .
NEUROSCIENCE, 1993, 53 (01) :77-89
[6]   IN-VIVO ANTISENSE INHIBITION OF PRODYNORPHIN EXPRESSION IN RAT STRIATUM - DOSE-DEPENDENCE AND SEQUENCE SPECIFICITY [J].
GEORGIEVA, J ;
HEILIG, M ;
NYLANDER, I ;
HERRERAMARSCHITZ, M ;
TERENIUS, L .
NEUROSCIENCE LETTERS, 1995, 192 (01) :69-71
[7]   ELECTRICAL ACTIVATION AND C-FOS MESSENGER-RNA EXPRESSION IN RAT NEUROSECRETORY NEURONS AFTER SYSTEMIC ADMINISTRATION OF CHOLECYSTOKININ [J].
HAMAMURA, M ;
LENG, G ;
EMSON, PC ;
KIYAMA, H .
JOURNAL OF PHYSIOLOGY-LONDON, 1991, 444 :51-63
[8]   DETAILED ANALYSIS OF BLOOD OXYTOCIN LEVELS DURING SUCKLING AND PARTURITION IN THE RAT [J].
HIGUCHI, T ;
TADOKORO, Y ;
HONDA, K ;
NEGORO, H .
JOURNAL OF ENDOCRINOLOGY, 1986, 110 (02) :251-256
[9]   CORTICOTROPIN-RELEASING FACTOR-IMMUNOREACTIVE NEURONS OF THE PARAVENTRICULAR NUCLEUS BECOME VASOPRESSIN POSITIVE AFTER ADRENALECTOMY [J].
KISS, JZ ;
MEZEY, E ;
SKIRBOLL, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (06) :1854-1858
[10]   ACTION OF ENDOGENOUS OXYTOCIN WITHIN THE PARAVENTRICULAR OR SUPRAOPTIC NUCLEI - A POWERFUL LINK IN THE REGULATION OF THE BURSTING PATTERN OF OXYTOCIN NEURONS DURING THE MILK-EJECTION REFLEX IN RATS [J].
LAMBERT, RC ;
MOOS, FC ;
RICHARD, P .
NEUROSCIENCE, 1993, 57 (04) :1027-1038