Summary
In an attempt to determine the conditions which permit central 5-HT neurons to respond to a chemical injury of their axons by sprouting and regeneration, the pattern and time-course of recovery of 5-HT concentrations and regrowth of bulbospinal 5-HT axons were evaluated in rats subjected to intraventricular treatment with either 75 μg 5,6- or 150 μg 5,7-DHT. While 5,6-DHT treatment is followed by a significant recovery of 5-HT concentrations in the telodiencephalon, brainstem and upper part of the spinal cord within 3 months, there is no significant restoration of the severely depleted 5-HT levels in the telodiencephalon and spinal cord, and only limited recovery in 5-HT content of the brainstem preparation after 5,7-DHT.
These differences conform to the observation of widespread and effective regrowth and regeneration of the bulbospinal 5-HT neurons in the 5,6-DHT treated lower brainstem and upper spinal cord but restricted and localized sprouting efforts in the 5,7-DHT treated lower medulla oblongata. This could be explained by a cell body near lesion of the non-terminal indoleamine axons by 5,7-DHT which results in a late retrograde, irreversible degeneration of most of the indoleamine pericarya from group B1 and many of group B3.
It is concluded that the preservation of a critical length of the main axon and part of its collaterals is necessary for the neuron's survival, and that the individual pattern of the neuropil architecture of brain centres which are invaded by the axonal sprouts may significantly influence their growth characteristics and thus either favour or impede their chance to reestablish connections with their original effector. Aberrant, localized, intense sprouting of drug-damaged axons may in itself reflect the need of the neuron—deprived of most of its axonal tree—to reestablish its original total axonal length by multiple branching.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Baumgarten, H. G.: Biogenic monoamines in the cyclostome and lower vertebrate brain. Progr. Histochem. Cytochem. 4, 1 (1972)
Baumgarten, H. G., Björklund, A., Holstein, A. F., Nobin, A.: Chemical degeneration of indoleamine axons in the rat brain by 5,6-dihydroxytryptamine. An ultrastructural study. Z. Zellforsch. 129, 256–271 (1972a)
Baumgarten, H. G., Björklund, A., Horn, A. S., Schlossberger, H. G.: Studies on the neurotoxic properties of hydroxylated tryptamines. In: Dynamics of degeneration and regeneration in neurons (K. Fuxe, L. Olson, Y. Zotterman, eds.), p. 153–167. Oxford, New York: Pergamon Press 1974
Baumgarten, H. G., Björklund, A., Lachenmayer, L., Nobin, A.: Evaluation of the effects of 5,7-dihydroxytryptamine on serotonin and catecholamine neurons in the rat CNS. Acta physiol. scand. Suppl. 391 (1973a)
Baumgarten, H. G., Björklund, A., Lachenmayer, L., Nobin, A., Stenevi, U.: Long-lasting selective depletion of brain serotonin by 5,6-dihydroxytryptamine. Acta physiol. scand Suppl. 373 (1971)
Baumgarten, H. G., Evetts, K. D., Holman, R. B., Iversen, L. L., Vogt, M., Wilson, G.: Effects of 5,6-dihydroxytryptamine on monoaminergic neurons in the central nervous system of the rat. J. Neurochem. 19, 1587–1597 (1972b)
Baumgarten, H. G., Lachenmayer, L.: Chemically induced degeneration of indolamine containing neurons in rat brain. Brain Res. 38, 228–232 (1972a)
Baumgarten, H. G., Lachenmayer, L.: 5,7-dihydroxytryptamine: Improvement in chemical lesioning of indoleamine neurons in the mammalian brain. Z. Zellforsch. 135, 399–414 (1972b)
Baumgarten, H. G., Lachenmayer, L., Björklund, A., Nobin, A., Rosengren, E.: Long-term recovery of serotonin concentrations in the rat CNS following 5,6-dihydroxytryptamine. Life Sci. 12, I, 357–364 (1973b)
Baumgarten, H. G., Lachenmayer, L., Schlossberger, H. G.: Evidence for a degeneration of indoleamine-containing nerve terminals in rat brain induced by 5,6-dihydroxytryptamine. Z. Zellforsch. 115, 553–569 (1972c)
Baumgarten, H. G., Victor, S. J., Lovenberg, W.: Effect of intraventricular injection of 5,7-dihydroxytryptamine on regional tryptophan hydroxylase of rat brain. J. Neurochem. 21, 251–253 (1973c)
Bertler, A.: Effect of reserpine on the storage of catecholamines in brain and other tissues. Acta physiol. scand. 51, 75–83 (1961)
Björklund, A., Falck, B., Owman, Ch.: Fluorescence microscopic and microspectrofluorimetric techniques for the cellular localization and characterization of biogenic amines. In: Methods of investigative and diagnostic endocrinology (S. A. Berson, ed.) vol. 1, The thyroid and biogenic amines (J. E. Rall, I. J. Kopin, eds.), p. 318–368. Amsterdam: North-Holland Publ. Co. 1972
Björklund, A., Nobin, A., Steveni, U.: Effects of 5,6-dihydroxytryptamine on nerve terminal serotonin and serotonin uptake in the rat brain. Brain Res. 53, 117–127 (1973a)
Björklund, A., Nobin, A., Steveni, U.: Regeneration of central serotonin neurons after axonal degeneration induced by 5,6-dihydroxytryptamine. Brain Res. 50, 214–220 (1973b)
Breese, G. R., Traylor, T. D.: Effect of 6-hydroxydopamine on brain norepinephrine and dopamine: Evidence for selective degeneration of catecholamine neurons. J. Pharmacol. exp. Ther. 174, 413–420 (1970)
Clemente, C. D.: Regeneration in the vertebrate central nervous system. Int. Rev. Neurobiol. 6, 258–302 (1964)
Dahlström, A., Fuxe, K.: Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta physiol. scand. 62, Suppl. 232 (1964)
Dahlström, A., Fuxe, K.: Evidence for the existence of monoamine-containing neurons in the central nervous system. II. Experimentally induced changes in the intraneuronal amine levels of bulbospinal neuron systems. Acta physiol. scand. 64, Suppl. 247, 1–36 (1965)
Nobin, A., Baumgarten, H. G., Björklund, A., Lachenmayer, L., Steveni, U.: Axonal degeneration and regeneration of the bulbospinal indoleamine neurons after 5,6-dihydroxytryptamine treatment. Brain Res. 56, 1–24 (1973)
Noble, E. P., Wurtman, R. J., Axelrod, J.: A simple and rapid method for injecting 3-Hnorepinephrine into the lateral ventricle of the rat brain. Life Sci. 6, 281–291 (1967)
Ungerstedt, U.: Histochemical studies on the effects of intracerebral and intraventricular injection of 6-hydroxydopamine on monoamine neurons in the rat brain. In: 6-Hydroxydopamine and catecholamine neurons (T. Malmfors, H. Thoenen, eds.), p. 101–127. Amsterdam, London: North Holland Publ. Co. 1971
Uretsky, N. J., Iversen, L. L.: Effects of 6-hydroxydopamine on noradrenaline containing neurons in the rat brain. Nature (Lond.) 221, 557–559 (1969)
Uretsky, N. J., Iversen, L. L.: Effects of 6-hydroxydopamine on catecholamine containing neurons in the rat brain. J. Neurochem. 17, 268–278 (1970)
Victor, S. J., Baumgarten, H. G., Lovenberg, W.: Depletion of tryptophan hydroxylase by 5,6-dihydroxytryptamine in rat brain, time course and regional differences. J. Neurochem. 22, 541–546 (1974)
Author information
Authors and Affiliations
Additional information
Supported by grants from the Deutsche Forschungsgemeinschaft. The authors are indebted to Rolf Franck for his technical assistance.
Supported by grants from the Swedish Medical Research Council (No. 04 X-3874 and 04 X-56).
Rights and permissions
About this article
Cite this article
Baumgarten, H.G., Björklund, A., Lachenmayer, L. et al. De- and regeneration of the bulbospinal serotonin neurons in the rat following 5,6-or 5,7-Dihydroxytryptamine treatment. Cell Tissue Res. 152, 271–281 (1974). https://doi.org/10.1007/BF00223949
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00223949