Suppression of BDNF-induced expression of neuropeptide Y (NPY) in cortical cultures by oxygen-glucose deprivation: A model system to study ischemic mechanisms in the perinatal brain

被引:3
作者
Barnea, A [1 ]
Roberts, J [1 ]
机构
[1] Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Dallas, TX 75390 USA
关键词
hypoxia; fetal; cell death; neuron; MAP-2;
D O I
10.1002/jnr.10191
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The aim of this study was to establish a culture system that can serve as a model to study hypoxic-ischemic mechanisms regulating the functional expression of NPY neurons in the perinatal brain. Using an aggregate culture system derived from the rat fetal cortex, we defined the effects of oxygen and glucose deprivation on NPY expression, using BDNF-induced production of NPY as a functional criterion. NPY neurons exhibited a differential susceptibility to oxygen and glucose deprivation. Although the neurons could withstand oxygen deprivation for 16 hr, they were dramatically damaged by 8 hr of glucose deprivation and by 1-4 hr of deprivation of both oxygen and glucose (N+Glu-). One-hour exposure to N+Glu- led to a transient inhibition (approximate to50%) of NPY production manifesting within 24 hr and recovering by 5 days thereafter, a 2-hr exposure to N+Glu- led to a sustained inhibition (50-75%) manifesting 1-5 days thereafter, and a 4-hr exposure to N+Glu- led to a total irreversible suppression of BDNF-induced production of NPY manifesting within 24 hr and lasting 8 days after re-supply of oxygen and glucose. Moreover, 1-hr exposure to N+Glu- led to a substantial and 4-hr exposure led to a total disappearance of immunostaining for MAP-2 and NPY but not for GFAP; indicating that neurons are the primary cell-type damaged by oxygen-glucose deprivation. Analysis of cell viability (LDH, MTT) indicated that progressive changes in cell integrity take place during the 4-hr exposure to N+Glu- followed by massive cell death 24 hr thereafter. Thus, we defined a culture system that can serve as a model to study mechanisms by which ischemic insult leads to suppression and eventually death of NPY neurons. Importantly, changes in NPY neurons can be integrated into the overall scheme of ischemic injury in the perinatal brain. (C) 2002 Wiley-Liss, Inc.
引用
收藏
页码:199 / 212
页数:14
相关论文
共 83 条
[1]   Does the onset of neonatal seizures correlate with the timing of fetal neurologic injury? [J].
Ahn, MO ;
Korst, LM ;
Phelan, JP ;
Martin, GI .
CLINICAL PEDIATRICS, 1998, 37 (11) :673-676
[2]   NEUROCHEMICAL CHANGES FOLLOWING OCCLUSION OF THE MIDDLE CEREBRAL-ARTERY IN RATS [J].
ALLEN, GV ;
CHEUNG, RTF ;
CECHETTO, DF .
NEUROSCIENCE, 1995, 68 (04) :1037-1050
[3]   NEUROPEPTIDE-Y DISTRIBUTION IN THE RAT-BRAIN [J].
ALLEN, YS ;
ADRIAN, TE ;
ALLEN, JM ;
TATEMOTO, K ;
CROW, TJ ;
BLOOM, SR ;
POLAK, JM .
SCIENCE, 1983, 221 (4613) :877-879
[4]   A thorny question: how does activity maintain dendritic spines? [J].
Andersen, P ;
Soleng, AF .
NATURE NEUROSCIENCE, 1999, 2 (01) :5-7
[5]   Predictive factors of early seizures after acute cerebrovascular disease [J].
Arboix, A ;
GarciaEroles, L ;
Massons, JB ;
Oliveres, M ;
Comes, E .
STROKE, 1997, 28 (08) :1590-1594
[6]   Relevance of early seizures for in-hospital mortality in acute cerebrovascular disease [J].
Arboix, A ;
Comes, E ;
Massons, J ;
Garcia, L ;
Oliveres, M .
NEUROLOGY, 1996, 47 (06) :1429-1435
[7]   Knock-out mice reveal a critical antiepileptic role for neuropeptide Y [J].
Baraban, SC ;
Hollopeter, G ;
Erickson, JC ;
Schwartzkroin, PA ;
Palmiter, RD .
JOURNAL OF NEUROSCIENCE, 1997, 17 (23) :8927-8936
[8]   Comparison of neurotrophin regulation of human and rat neuropeptide Y (NPY) neurons: Induction of NPY production in aggregate cultures derived from rat but not from human fetal brains [J].
Barnea, A ;
AguilaMansilla, N ;
Chute, HT ;
Welcher, AA .
BRAIN RESEARCH, 1996, 732 (1-2) :52-60
[9]   BRAIN-DERIVED NEUROTROPHIC FACTOR INDUCES FUNCTIONAL EXPRESSION AND PHENOTYPIC DIFFERENTIATION OF CULTURED FETAL NEUROPEPTIDE Y-PRODUCING NEURONS [J].
BARNEA, A ;
CHO, G ;
LU, G ;
MATHIS, M .
JOURNAL OF NEUROSCIENCE RESEARCH, 1995, 42 (05) :638-647
[10]   Induction of functional and morphological expression of neuropeptide Y (NPY) in cortical cultures by brain-derived neurotrophic factor (BDNF): evidence for a requirement for extracellular-regulated kinase (ERK)-dependent and ERK-independent mechanisms [J].
Barnea, A ;
Roberts, J .
BRAIN RESEARCH, 2001, 919 (01) :57-69