Morphological response of axotomized septal neurons to nerve growth factor

Septal efferent fibers from, the neurons in the medial septal nucleus are destroyed by fimbria‐fornix aspirative lesion. In the present study we used quantitative morphometric techniques to evaluate the response of these axotomized septal neurons to a constant infusion of nerve growth factor (NGF). By 2 weeks following the lesion, approximately 75% of the cholinergic neurons had degenerated in the untreated rats. The remaining cholinergic neurons showed few signs of the effect of the lesion when stained for a polyclonal antibody to ChAT and examined in 40‐μm‐thick sections. In 1‐μm‐thick sections the remaining ChAT‐immunoreactive (IR) neurons also appeared no different from the intact ChAT neurons. However, non‐ChAT‐IR neurons had a shrunken nucleus, while all other morphometric parameters appeared normal. NGF infusion protected most of the ChAT‐IR neurons from degenerating. The saved neurons had the same parameters as the undamaged ChAT‐IR neurons when examined in either 40‐μm‐ or 1‐μm‐thick sections. In addition, the shrunken appearance of the non‐ChAT‐IR neurons' nuclei was avoided by the NGF infusions.

[1]  F. Gage,et al.  Response of septal cholinergic neurons to axotomy , 1987, The Journal of comparative neurology.

[2]  F. Gage,et al.  Loss of GABAergic neurons in medial septum after fimbria-fornix transection , 1987, Neuroscience Letters.

[3]  F. Gage,et al.  A small-gauge cannula device for continuous infusion of exogenous agents into the brain , 1987, Experimental Neurology.

[4]  G. Kreutzberg,et al.  The localization and distribution of high affinity β-nerve growth factor binding sites in the central nervous system of the adult rat. A light microscopic autoradiographic study using [125I]β-nerve growth factor , 1987, Neuroscience.

[5]  L. F. Kromer.  Nerve growth factor treatment after brain injury prevents neuronal death. , 1987, Science.

[6]  R. Loy,et al.  Basal forebrain magnocellular neurons stain for nerve growth factor receptor: Correlation with cholinergic cell bodies and effects of axotomy , 1987, Journal of neuroscience research.

[7]  F. Gage,et al.  Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria fornix transection. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[8]  L. Hersh,et al.  Choline acetyltransferase immunoreactivity in neuritic plaques of Alzheimer brain , 1986, Neuroscience Letters.

[9]  F. Gage,et al.  Retrograde cell changes in medial septum and diagonal band following fimbria-fornix transection: Quantitative temporal analysis , 1986, Neuroscience.

[10]  F. Hefti,et al.  Nerve growth factor promotes survival of septal cholinergic neurons after fimbrial transections , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  L. Reichardt,et al.  Studies on the expression of the beta nerve growth factor (NGF) gene in the central nervous system: level and regional distribution of NGF mRNA suggest that NGF functions as a trophic factor for several distinct populations of neurons. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[12]  S. Skaper,et al.  An automated colorimetric microassay for neuronotrophic factors. , 1986, Brain research.

[13]  J. Schweitzer,et al.  Nerve growth factor receptor molecules in rat brain. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[14]  L. Olson,et al.  Development and regional expression of beta nerve growth factor messenger RNA and protein in the rat central nervous system. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[15]  E. Johnson,et al.  Characterization of the binding properties and retrograde axonal transport of a monoclonal antibody directed against the rat nerve growth factor receptor , 1985, The Journal of cell biology.

[16]  L. Hersh,et al.  Immunoaffinity Purification of Human Choline Acetyltransferase: Comparison of the Brain and Placental Enzymes , 1985, Journal of neurochemistry.

[17]  H. Thoenen,et al.  Levels of nerve growth factor and its mRNA in the central nervous system of the rat correlate with cholinergic innervation. , 1985, The EMBO journal.

[18]  D. Price,et al.  A modified histochemical technique to visualize acetylcholinesterase-containing axons. , 1985, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[19]  M. Schwab,et al.  Specific retrograde transport of nerve growth factor (NGF) from neocortex to nucleus basalis in the rat , 1984, Brain Research.

[20]  F. Gage,et al.  Cells of origin of the ventral cholinergic septohippocampal pathway undergoing compensatory collateral sprouting following fimbria-fornix transection , 1984, Neuroscience Letters.

[21]  Fred H. Gage,et al.  Reinnervation of the partially deafferented hippocampus by compensatory collateral sprouting from spared cholinergic and noradrenergic afferents , 1983, Brain Research.

[22]  A. Levey,et al.  Distribution of cholinergic neurons in rat brain: Demonstrated by the immunocytochemical localization of choline acetyltransferase , 1983, The Journal of comparative neurology.

[23]  S H Appel,et al.  A unifying hypothesis for the cause of amyotrophic lateral sclerosis, parkinsonism, and alzheimer disease , 1981, Annals of neurology.

[24]  S. Hsu,et al.  Protein A, avidin, and biotin in immunohistochemistry. , 1981, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[25]  H. Thoenen,et al.  Nerve growth factor (NGF) in the rat CNS: Absence of specific retrograde axonal transport and tyrosine hydroxylase induction in locus coeruleus and substantia nigra , 1979, Brain Research.

[26]  T. Powell,et al.  STUDIES OF THE CONNEXIONS OF THE FORNIX SYSTEM , 1954, Journal of neurology, neurosurgery, and psychiatry.