Regional CNS uptake of blood‐borne nerve growth factor

Nerve growth factor (NGF), in addition to being a neurotrophic substance, has effects on the endocrine and immune systems. For example, intravenous injection of NGF results in a cascade of events leading to an increase in glucocorticoid secretion. While this response appears to be mediated centrally, there has been no evidence that circulating NGF has access to the CNS. Using intravenous injections of 125I‐NGF, we find specific uptake at 1 hr but none at 6 hr, into homogenates of the basal forebrain, cerebellum, frontal cortex, hippocampus, and olfactory bulb. By autoradiography, uptake is localized to circumventricular organs, deep layers of the cerebellum, and all layers of the hippocampal region CA1, but not the dentate gyrus. Thus, uptake of blood‐borne NGF could affect the hypothalamic‐pituitary‐adrenal axis via binding to NGF receptors present in the hippocampus. However, the sources of endogenous NGF, the mechanism of access through the blood‐brain barrier, the eventual fate of NGF entering from the blood, and the physiological significance of this uptake remain to be elucidated. © 1994 Wiley‐Liss, Inc.

[1]  R. Simone,et al.  Nerve growth factor released into the bloodstream following intraspecific fighting induces mast cell degranulation in adult male mice , 1990, Brain, Behavior, and Immunity.

[2]  M. Goedert,et al.  Stimulation of the pituitary-adrenocortical axis and induction of tyrosine hydroxylase by nerve growth factor are not dependent on mouse submaxillary gland isorenin , 1981, Brain Research.

[3]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[4]  V. M. Pickel,et al.  Electron microscopic immunocytochemical localization of tyrosine hydroxylase in the area postrema of rat , 1982, The Journal of comparative neurology.

[5]  U. Otten,et al.  Stimulation of the pituitary-adrenocortical axis by nerve growth factor , 1979, Nature.

[6]  Q. Yan,et al.  An immunohistochemical study of the nerve growth factor receptor in developing rats , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[7]  S. Soinila,et al.  Biological demonstration of nerve growth factor in the rat pituitary gland , 1989, Neuroscience.

[8]  R. Simone,et al.  Social status and nerve growth factor serum levels after agonistic encounters in mice , 1990, Physiology & Behavior.

[9]  E. Shooter,et al.  Characterization and isolation of proteolytically modified nerve growth factor. , 1976, Biochemistry.

[10]  J. Lakshmanan,et al.  Intraventricular administration of nerve growth factor induces ornithine decarboxylase in peripheral tissues of the rat. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[11]  R. Stach,et al.  Sequestration of 125I-labeled beta nerve growth factor by sympathetic neurons. , 1980, The Journal of biological chemistry.

[12]  M. Salcman,et al.  Transcytotic pathway for blood-borne protein through the blood-brain barrier. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[13]  E. Pioro,et al.  Distribution of nerve growth factor receptor-like immunoreactivity in the adult rat central nervous system. Effect of colchicine and correlation with the cholinergic system—II. Brainstem, cerebellum and spinal cord , 1990, Neuroscience.

[14]  C. Hulsebosch,et al.  Penetration of IgGs into the neuraxis of the neonatal rat , 1989, Neuroscience Letters.

[15]  G. Higgins,et al.  Localization of nerve growth factor receptor messenger RNA and protein in the adult rat brain , 1989, Experimental Neurology.

[16]  J. Lakshmanan,et al.  Epidermal Growth Factor in Synaptosomal Fractions of Mouse Cerebral Cortex , 1986, Journal of neurochemistry.

[17]  J. Lakshmanan.  β‐Nerve Growth Factor Measurements in Mouse Serum , 1986 .

[18]  G. Taglialatela,et al.  Nerve growth factor modulates the activation of the hypothalamo-pituitary-adrenocortical axis during the stress response. , 1991, Endocrinology.

[19]  P. Distefano,et al.  Developmental regulation of human truncated nerve growth factor receptor , 1991, Annals of neurology.

[20]  K. Nagaiah,et al.  The permissive effect of cortical steroids on the induction of brain ornithine decarboxylase by nerve growth factor. , 1978, Biochemical and biophysical research communications.

[21]  J. Kordower,et al.  Nerve growth factor receptor immunoreactivity in the nonhuman primate (Cebus apella): Distribution, morphology, and colocalization with cholinergic enzymes , 1988, The Journal of comparative neurology.

[22]  D. Marchetti,et al.  Nerve Growth Factor Receptors in Human Neuroblastoma Cells , 1987, Journal of neurochemistry.

[23]  L. Greene.  A quantitative bioassay for nerve growth factor (NGF) activity employing a clonal pheochromocytoma cell line , 1977, Brain Research.

[24]  E. Alleva,et al.  Aggressive behavior induces release of nerve growth factor from mouse salivary gland into the bloodstream. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[25]  A. Prochiantz,et al.  Lipopolysaccharide-stimulated rat brain macrophages release NGF in vitro. , 1989, Developmental biology.

[26]  F. Keller,et al.  Nerve growth factor increases in adult rat brain after hypoxic injury , 1989, Neuroscience Letters.

[27]  U. Stephani,et al.  Nerve growth factor (NGF) in serum: Evaluation of serum NGF level with a sensitive bioassay employing embryonic sensory neurons , 1987, Journal of neuroscience research.

[28]  P. Claude,et al.  Expression of NGF receptor in the developing and adult primate central nervous system , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[29]  R. Loy,et al.  Localization and development of nerve growth factor-sensitive rat basal forebrain neurons and their afferent projections to hippocampus and neocortex , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[30]  G. Lynch,et al.  A comparison of the role of the motor cortex in recovery from cerebellar damage in young and adult rats. , 1974, Behavioral biology.