NGF and Anti-NGF: Evidence against Effects on Fiber Growth in Locus coeruleus from Cultures of Perinatal CNS Tissues

Olson, Lar̀s; Ebendal, Ted; Seiger, Åke

doi:10.1159/000112451

Cited by 51 publications

(7 citation statements)

References 26 publications

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“…Nerve growth factor, which strongly increased the density of cholinergic fibres and elevated the levels of cholinergic enzymes in septo-hippocampal co-cultures (G3hwiler et al, 1987, 1989), had no apparent morphological effect on the development of TH-positive cells in co-cultures of brainstem and hippocampus. This observation is consistent with previous studies on central noradrenergic cells in situ (Schwab et al, 1979) and in vitro (Dreyfus et al, 1980;Olson et al, 1979;Victorov et al, 1979). In variance to cholinergic fibres in septo-hippocampal co-cultures (Gahwiler et al, 1989;Gahwiler and Knopfel, unpublished observations), following several weeks in vitro TH-positive fibres originating in cultures of the LC were still present in the outgrowth areas where they formed whirl-like endings.…”

Section: Discussionsupporting

confidence: 94%

Organotypic Co‐Cultures of Rat Locus Coeruleus and Hippocampus

Knöpfel

Rietschin

Gähwiler

1989

Eur J of Neuroscience

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Slices from the brainstem at the level of the locus coeruleus and from the hippocampus of 5 - 7 day old rats were co-cultured using the roller tube technique. After 2 - 6 weeks in vitro the co-cultures were examined with antibodies raised against tyrosine-hydroxylase (TH). The cultures derived from the brainstem consistently contained a bilateral cluster of TH-positive neurons with 3 - 5 long slender dendrites. These neurons typically gave rise to several fine varicose fibres reminiscent of catecholaminergic axons. A morphologically distinct group of TH-positive neurons was detected in the hippocampal slices. The vast majority of them were located in the subicular region and a smaller number in the CA1/CA3 region of the hippocampal explant. TH-positive neurons were also present in mono-cultures of hippocampus or brainstem. In the vast majority of co-cultures, a variable number of TH-immunoreactive fibres of neurons derived from the locus coeruleus grew over considerable distances to terminate finally within the co-cultured hippocampus where they branched to form a diffuse innervation plexus with club-like endings. Even after several weeks in vitro, TH-positive fibres could still be seen exploring sites which were not related to their target, including the cell-free areas surrounding the cultures. Fibres in these outgrowth areas formed whirl-like endings. TH-positive fibres arising from neurons located in the hippocampus, on the other hand, did not branch extensively and never projected over long distances. Nerve growth factor had no apparent trophic effect on TH-positive cells in the hippocampus, the locus coeruleus, or in the co-cultures.

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Section: Discussionsupporting

confidence: 94%

Organotypic Co‐Cultures of Rat Locus Coeruleus and Hippocampus

Knöpfel

Rietschin

Gähwiler

1989

Eur J of Neuroscience

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“…About the same time that it was demonstrated that central catecholaminergic neurons do not respond to NGF (Konkol et al 1978;Schwab et al 1979;Olson et al 1979;Dreyfus et al 1980) and do not express NGF receptors (Schwab et al 1979), but that NGF is transported specifically from the hippocampus to septal cholinergic neurons (Schwab et al 1979), several laboratories reported that lesioning the septo-hippocampal pathway resulted in an ingrowth of perivascular sympathetic fibers into the hippocampus (Loy and Moore 1977;Stenevi and BjOrklund 1978;Crutcher et al 1979;Crutcher and Davis 1981). It was also demonstrated that only a fimbrial transection could trigger this reactive ingrowth of peripheral sympathetic nerve fibers.…”

Section: The Role Played By Fimbria Lesion Experiments In the Elucidamentioning

confidence: 99%

The physiological function of nerve growth factor in the central nervous system: Comparison with the periphery

Thoenen¹,

Bandtlow²,

Heumann³

1987

Reviews of Physiology, Biochemistry and Pharmacology

507

175

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“…However, both the presence and potential physiological function of NGF in the central nervous system (CNS) has remained elusive (3). The characteristic responses of peripheral adrenergic neurons following NGF or anti-NGF antibody injection have not been observed after similar application into the CNS (4)(5)(6)(7)(8)(9)(10)(11).…”

mentioning

confidence: 99%

Development and regional expression of beta nerve growth factor messenger RNA and protein in the rat central nervous system.

Whittemore¹,

Ebendal²,

Lärkfors³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

381

171

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The presence of nerve growth factor (NGF) mRNA and protein in the rat central nervous system is documented. Blot-hybridization analysis showed an abundance of NGF mRNA in the hippocampus, cerebral cortex, and olfactory bulb. Enzyme immunoassay confirmed significant levels of a NGF-like protein in the hippocampus and cerebral cortex. Bioassay of a NGF-like immunoaffinity-purified protein from these regions was physiologically indistinguishable from NGF. Immunohistochemistry revealed a widespread distribution of NGF-like reactivity in the adult brain, preferentially in fiber tracts. NGF mRNA accumulation began at birth, with adult levels reached 3 weeks postnatally. Enzyme immunoassay detected the presence of a NGF-like protein in the embryonic rat brain. Postnatally, the level of NGF-like protein reached a maximum at 3 weeks. Additionally, a distinct fetal form of NGF may exist.,B nerve growth factor (NGF) is essential for the development and maintenance of sensory and sympathetic neurons in the peripheral nervous system (PNS) (1, 2). However, both the presence and potential physiological function of NGF in the central nervous system (CNS) has remained elusive (3). The characteristic responses of peripheral adrenergic neurons following NGF or anti-NGF antibody injection have not been observed after similar application into the CNS (4-11).In the PNS, NGF is taken up by adrenergic terminals and also retrogradely transported to the cell body (2). In the CNS, injected NGF was specifically retrogradely transported from the hippocampus to the medial septum and the diagonal band of Broca (9) and also from the neocortex to the nucleus basalis (12), presumably in cholinergic neurons. NGF induced choline acetyltransferase in neonatal rat cortex, hippocampus, septum (10), and striatum (11), but not in adult hippocampus (13).Thus, NGF may have a physiological function in the CNS, and affect cholinergic neurons. Initial indication of endogenous NGF in the CNS was obtained by immunohistochemistry in the fetal rat (14, 15). NGF cDNA clones have been isolated from male mouse submaxillary glands (16,17), and Shelton and Reichardt (18) recently detected NGF mRNA in the rat brain. Subsequently, NGF mRNA and an NGF-like protein have been described in some regions of the adult rat brain (19).In the present study, we demonstrate the developmental time course as well as the adult regional distribution of both NGF mRNA and protein in the adult rat brain. Finally, using a bioassay, we show that the adult brain contains nerve growth-stimulating activity typical of purified NGF. Our results demonstrate that NGF is expressed in the adult rat CNS with regional specificity and suggests the existence of a fetal form of NGF. MATERIALS AND METHODSPreparation of RNA and Blot-Hybridization Analysis. Total RNA from the brains of Sprague-Dawley rats (Alab, Stockholm, Sweden) was prepared (20), and poly(A)+ RNA, isolated by oligo(dT) chromatography (21), was separated on 1% agarose gels containing 0.7% formaldehyde and transferred to nitrocel...

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NGF and Anti-NGF: Evidence against Effects on Fiber Growth in Locus coeruleus from Cultures of Perinatal CNS Tissues

Cited by 51 publications

References 26 publications

Organotypic Co‐Cultures of Rat Locus Coeruleus and Hippocampus

Organotypic Co‐Cultures of Rat Locus Coeruleus and Hippocampus

The physiological function of nerve growth factor in the central nervous system: Comparison with the periphery

Development and regional expression of beta nerve growth factor messenger RNA and protein in the rat central nervous system.

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