Hostname: page-component-77c89778f8-m8s7h Total loading time: 0 Render date: 2024-07-16T09:26:50.672Z Has data issue: false hasContentIssue false
  • English
  • Français

The Cerebellar Serotoninergic System and its Possible Involvement in Cerebellar Ataxia

Published online by Cambridge University Press:  18 September 2015

P. Trouillas
P. Trouillas*
Affiliation:
Neurology Service and Ataxia Research Center, Hopital Neurologique, 59 Bd Pinel, Lyon, France 69003
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

A review concerning the characteristics of the cerebellar serotoninergic system is presented. In rat, cat and oppossum, the perikarya of origin are located in the brain stem raphe nuclei and in other brainstem structures. The projections to the cerebellar layers and deep nuclei include synaptic connections, but also non synaptic terminals, espedaily in a diffuse cortical plexus. Serotoninergic receptors have been described: 5-HT1B in the molecular layer and 5-HT2 in the inferior olive. Serotonin exerts neurophysiological effects on several target cells, directly or indirectly, presynaptically or postsynaptically. A modulatory effect on Purkinje cells is well documented. In thiamine deprived animals, a specific serotoninergic cerebellar syndrome includes a selective degeneration of the serotoninergic cerebellar system, an increase of the 5-HIAA cerebellar values and an exaggerated serotoninergic turnover. In human here-doataxias (Friedreich’s ataxia and cerebellar cortical atrophy), serotoninergic disturbances have been observed in the CSF, including low 5-HIAA values and an increased serotoninergic turnover. Therapeutic results have been obtained with L-5-HTP, a precursor of serotonin, in several conditions presenting cerebellar ataxia. L-5-HTP resistance of olivo-pontocerebellar atrophies may be explained by the destruction of serotonin-sensitive target cells, especially Purkinje cells.

Type
Abstract
Information
Canadian Journal of Neurological Sciences , Volume 20 , Issue S3 , May 1993 , pp. S78 - S82
Copyright
Copyright © Canadian Neurological Sciences Federation 1993

References

REFERENCES

1.Trouillas, P, Garde, A, Robert, JM, et al.Régression du syndrome cérébelleux sous traitement à long terme par le 5-HTP ou l’assodation 5-HTP-Bensérazide: vingt-cinq observations quantifiées et traitées par ordinateur. Rev Neurol 1980, 136: 891.Google Scholar
2.Trouillas, P, Garde, A, Robert, JM, Adeleine, P.Régression de l’ataxie cérébelleuse humaine sous administration à long terme de 5-hydroxytryptophane. CR Acad Sci 1981; 292: 119–122.Google Scholar
3.Trouillas, P, Garde, A.Regression of cerebellar ataxia with long term 5-HTP therapy assessed by computerized data processing. In: Abstracts of the 12th World Congress of Neurology, Kyoto, Japan, Sept 20–25, 1981. Princeton, NJ, Excerpta Medica International Congress Series, 548, 1981, 382.Google Scholar
4.Trouillas, P, Garde, A, Robert, JM, et al.Régression du syndrome cérébelleux sous administration à long terme de 5-HTP ou de l’association 5-HTP-benzérazide: vingt-six observations quantifiées et traitées par ordinateur. Rev Neurol 1982; 138: 415–435.Google Scholar
5.Hokfelt, T, Fuxe, K.Cerebellar monoamine nerve terminals, a new type of afferent fibers to the cortex cerebelli. Exp Brain Res 1969; 9: 63–72.CrossRefGoogle Scholar
6.Fuxe, K, Jonsson, G.Further mapping of cerebral 5-hydroxy-tryptamine neurons: studies with the neurotoxic dihydroxy-tryptamines. In: “Advances in Biochemical Psycho-pharmacology, New-York: Raven Press, 1974, 1–12.Google Scholar
7.Shinnar, S, Maciewicz, RJ, Shofer, RJ.A raphe projection to cat cerebellar cortex. Brain Res 1975; 97: 139–143.CrossRefGoogle ScholarPubMed
8.Sato, Y, Kanasaki, T, Karashi, K.Afferent projections from the brain-stem to the three floccular zones in cats II. Mossy fiber projections. Brain Res 983; 272: 37–48.Google Scholar
9.Batini, C., Corvisier, J, Hardy, O.Projections des noyaux réticulaires bulbaires et des noyaux du raphé sur les lobules Vl et VII du cortex cérébelleux du chat. CR Acad Sci 1977; 284: 1805–1806.Google Scholar
10.Bobillier, P, Seguin, S, Petitjean, F, et al.The raphe nuclei of the cat brain stem: a topographical atlas of their afferent projections as revealed by autoradiography. Brain Res 1976; 113: 449–486.CrossRefGoogle Scholar
10.Bishop, GA, HO, RH.The distribution and origin of serotoninimmunoreactivity in the rat cerebellum. Brain Res 1985.CrossRefGoogle Scholar
12.Chan-Palay, V.Fine structure of labeled axons in the cerebellar cortex and nuclei of rodents and primates after intraventricular infusions with tritiated serotonin. Anat Embryol 1975; 148: 235–265.CrossRefGoogle ScholarPubMed
13.Chan-Palay, V.Cerebellar Dentate Nucleus Organization, Cytology and Transmitters. New York, Springer Verlag NY Inc, 1977.CrossRefGoogle Scholar
14.Chan-Palay, V.Indoleamine neurons and their processes in the normal rat brain and in chronic diet-induced thiamine deficiency, demonstrated by 3H-serotonin. J Comp Neurol 1979; 176: 467–494.CrossRefGoogle Scholar
15.Beaudet, A, Sotelo, C.Synaptic remodeling of serotonin axon terminals in rat agranular cerebellum. Brain Res; 331: 195–207.Google Scholar
16.Takeuchi, Y, Kimura, H, Sano, Y.Immunohistochemical demonstrations of serotonin-containing nerve fibers in the cerebellum. Cell Tiss Res 1982; 26: 1–12.Google Scholar
17.Bishop, GA, Ho, RH, King, JG.Localization of serotonin immunore-activity in the oppossum cerebellum. J Comp Neurol 1985; 235: 301–321.CrossRefGoogle Scholar
18.Wiklund, L, Bjorklund, A, Sjolund, B.The indolaminergic innervation of the inferior olive: I. Convergence with direct spinal afferents in the areas projecting to the cerebellar anterior lobe. Brain Res 1977; 131: 1–21.CrossRefGoogle Scholar
19.Sjolund, B, Bjorklund, A, Wiklund, L.The indolaminergic innervation of the inferior olive: II. Relations to harmaline-induced tremor. Brain Res 1977; 131: 23–27.CrossRefGoogle Scholar
20.Wiklund, L, Descarries, L, Mollgard, K.Serotonergic axon terminais in the rat dorsal accessory olive: normal ultrastructure and light microscopic demonstration of regeneration after 5,6-dihydroxytryptamine lesioning. J Neurocytol 1981; 10: 1009–1102.CrossRefGoogle Scholar
21.Pare, M, Descarries, L, Wiklund, L.Innervation and reinnervation of rat inferior olive by neurons containing serotonin and substance P: an immunohistochemical study after 5,6-dihydroxytryptamine lesioning. J Neurocytol 1987; 16: 155–160.CrossRefGoogle ScholarPubMed
22.Tsang, D, Lai, G.Accumulation of cyclic adenosine 3’5-monophosphate in human cerebellar cortex slices: effects of monoamine receptor agonists and antagonists. Brain Res 1978; 140: 307–313.CrossRefGoogle ScholarPubMed
23.Headley, PM, Lodge, D.Studies on field potentials and on single cells in the inferior olivary complex of the rat. Brain Res 1976; 101: 445–459.CrossRefGoogle ScholarPubMed
24.Palacios, JM, Pompeiano, M, Pompeiano, O, Mengod, G.Visualization of 5-HT receptors in the cerebellum and related brain stem areas. In: Trouillas, P, Fuxe, K, eds. Serotonin, the Cerebellum and Ataxia. Raven Press, New-York, 1993: 167–177.Google Scholar
25.Saudou, F, Maroteaux, L, Amlaiky, N, et al.The mouse 5-HT1B serotonin receptor: cloning, functional expression and localization in motor control centers. In: Trouillas, P, Fuxe, K, eds. Serotonin, the Cerebellum and Ataxia. Raven Press, New-York, 1993: 201–209.Google Scholar
26.Chan-Palay, V, Höchli, M, Jentsch, B., et al.A quantitative study of the raphe serotonin neurons in the normal human brain stem. In: Trouillas, P, Fuxe, K, eds. Serotonin, the Cerebellum and Ataxia. Raven Press, New-York, 1993: 37–49.Google Scholar
27.Bloom, FC, Hoffer, BJ, Sigrins, GR, Barker, JL, Nicoli, RA.Effects of serotonin on central neurons: microiontophoretic administration. Fed Proc 1972; 31:97–106.Google ScholarPubMed
28.Strahlendorf, JC, Lee, M, Strahlendorf, HK.Effects of serotonin on cerebellar Purkinje cells are dependent on the baseline firing rate. Exp Brain Res 1984; 56: 50–59.CrossRefGoogle ScholarPubMed
29.Strahlendorf, JC, Strahlendorf, HK, Lee, M.Enhancement of cerebellar Purkinje cell complex discharge activity by microiontophoretic serotonin. Exp Brain Res 1986; 61: 614–624.CrossRefGoogle ScholarPubMed
30.Lee, M, Strahlendorf, JC, Strahlendorf, HK.Picrotoxin but not bicu-culline antagonizes 5-hydroxy-tryptamine-induced inhibition of cerebellar Purkinje neurons. Exp Neurol 1987; 97: 577–591.CrossRefGoogle ScholarPubMed
31.Strahlendorf, JC, Strahlendorf, HK, Barnes, CD.Modulation of cerebellar neuronal activity by raphe stimulation. Brain Res 1979; 169: 565–569.CrossRefGoogle ScholarPubMed
32.Gardette, R, Krupa, M, Crepel, F.Differential effects of serotonin on the spontaneous discharge and on the excitatory aminoacid-induced responses of deep cerebellar nuclei neurons in rat cerebellar slices. Neuroscience 1987; 23: 491–500.CrossRefGoogle Scholar
33.Gardette, R, Crepel, F.Differential modulation by serotonin of the responses induced by excitatory amino-acids in cerebellar nuclei neurons and Purkinje cells. In: Trouillas, P, Fuxe, K, eds. Serotonin, the Cerebellum and Ataxia. Raven Press, New-York, 1993: 225–236.Google Scholar
34.Raiteri, M, Maura, G, Bonanno, G, Pittaluga, A.Differential pharma cology and function of two 5-HT1 receptors modulating transmitter release in rat cerebellum. J Pharmacol Exp Ther 1986; 237: 644–648.Google Scholar
35.Raiteri, M, Maura, G, Lottero, P, Gastaldo, L.Serotonergic control of glutamatergic systems in the cerebellum. In: Trouillas, P, Fuxe, K, eds. Serotonin, the Cerebellum and Ataxia. Raven Press, New-York, 1993: 155–166.Google Scholar
36.Weiss, M, Pellet, J.Raphe-cerebellum interactions. II Effects of mid-brain raphe stimulations and harmaline administration on simple unit activity of cerebellar cortical cells in the rat. Exp Brain Res 1982; 68: 171–76.CrossRefGoogle Scholar
37.Chan-Palay, V, Plaitakis, A, Nicklas, N., Beri, S.Autoradiographic demonstration of loss of labeled indoleamine axons of the cerebellum in chronic diet-induced thiamine deficiency. Brain Res 1977; 138: 380–384.CrossRefGoogle ScholarPubMed
38.Plaitakis, A, Van Woert, MH, Hwang, EC, Beri, S.Thiamine deficiency: selective impairment of the cerebellar serotonergic system. J Neurochem 1978; 31: 1087–1089.CrossRefGoogle Scholar
39.Plaitakis, A, Nicklas, JN, Beri, S.Thiamine deficiency: selective impairment of the cerebellar serotonergic system. Neurology 1978; 28: 691–698.CrossRefGoogle ScholarPubMed
40.Plaitakis, A, Hwang, EC, Van Woert, MH, Szilagui, PA, Beri, S.Effect of thiamine deficiency on brain neurotransmitter systems. Ann N YA cad Sci 1982: 367–381.CrossRefGoogle Scholar
41.Kuhar, MJ, Roth, RH, Aghajamian, GK.Synaptosomes from fore-brains of rats with midbrain raphe lesions: selective reduction of serotonin uptake. J Pharmacol Exp Ther 1972; 181: 36–45.Google ScholarPubMed
42.Ghetti, B., Perry, KW, Fuller, RW.Serotonin concentration and turnover in cerebellum and other brain regions of pcd mutant mice. Brain Res 1988; 457: 367–371.CrossRefGoogle Scholar
43.Oshugi, K, Adachi, K, Ando, K.Serotonin metabolism in the CNS in cerebellar ataxia mice. Experientia 1986; 42: 1245–1247.Google Scholar
44.Ichikawa, N.Study on monoamine metabolite contents of cere brospinal fluid in patients with neurodegenerative diseases. Tohoku J Exp Med 1986; 150: 435–446.CrossRefGoogle Scholar
45.Trouillas, P., Charles, N., Renaud, B., Eynard, P.CSF serotonergi cabnormalities in acquired and hereditary ataxias. In: Trouillas, P, Fuxe, K, eds. Serotonin, the Cerebellum and Ataxia. Raven Press, New-York, 1993: 311–322.Google Scholar
46.Baron, DN, Dent, CE, Harris, H, Jepson, JB.Hereditary pellagra like skin rash with temporary cerebellar ataxia, constant renal amino-aciduria, and other bizarre biochemical features. Lancet 1956; 2: 421–428.CrossRefGoogle Scholar
47.Southren, AL, Warner, RRP, Christoff, N, et al.An unusual neuro logic syndrome associated with hyperserotoninemia. N Engl J Med 1959: 260 1265–1268.CrossRefGoogle Scholar
48.Trouillas, P, Brudon, F, Adeleine, P.Improvement of cerebellar ataxia with levorotary form of 5-hydroxytryptophan. A double-blind study with quantified data processing. Arch Neurol 1988; 45; 1217–1222.CrossRefGoogle Scholar
49.Rascol, A, Clanet, M, Monstrastruc, JL, et al.L-5-hydroxytryptophan in the cerebellar syndrome treatment. Biomedicine 1981; 35; 112–113.Google Scholar
50.Wessel, K., Diener, HC, Dichgans, J.Vorläufige, Therapieergebnisse mit 5-hydroxy-tryptophan bei Friedreich’s ataxie und zerebelläre atrophie. Psycho 1985; 11; 436–437.Google Scholar
51.Wessel, K, Diener, HC, Dichgans, J.Long-loop reflexes and posturalataxia: follow-up study with and without treatment by 5-HTP in patients with Friedreich ataxia. In: Amblard, V, Berthoz, A, Clarac, F, eds. Posture and Gait, Development Adaptation and Modulation. Elsevier, (Amsterdam) 1988: 237–244.Google Scholar
52.Mertens, HG, Kohlepp, W.Spino-cerebelläre Atrophien - Diagnose und Therapie. Verh Dtsch Ges Neurol 1987; 4: 294–300.Google Scholar
53.Trouillas, P.L-5-Hydroxytryptophan treatment in hereditary and acquired ataxia. Movement Disorders 1990; 5, suppi 1: 6.Google Scholar
54.Trouillas, P.The serotonergic hypothesis of cerebellar ataxia and its pharmacological consequences. In: Trouillas, P, Fuxe, K, eds. Serotonin, the Cerebellum and Ataxia. Raven Press (New York) 1993: 323–334.Google Scholar