Studies on neurotransmitter markers and neuronal cell density in the cerebellar system in olivopontocerebellar atrophy and cortical cerebellar atrophy

doi:10.1016/0022-510X(85)90059-0

Journal of the Neurological Sciences

Volume 71, Issues 2–3, December 1985, Pages 193-208

https://doi.org/10.1016/0022-510X(85)90059-0 Get rights and content

Abstract

Glutamate, aspartate and γ-aminobutyrate (GABA) concentrations and choline acetyltransferase (ChAT) activity were measured in postmortem cerebellar cortical areas and brainstem nuclei of 10 normal controls, 5 patients of olivopontocerebellar atrophy (OPCA) with multiple system atrophy (MSA) and 2 patients of cortical cerebellar atrophy (CCA). In addition, the neuronal cell density in the cerebellar cortex and the brainstem nuclei was determined, and the correlation between neurotransmitter markers and the neuronal cell densities were investigated. Glutamate and aspartate concentrations in the cerebellar cortical tissues were markedly varied from case to case of MSA (OPCA) and CCA patients. However, glutamate concentration in the anterior vermis showed a positive correlation coefficient with the density of granule cells (r = 0.554, 0.05 < P < 0.10) and, those in the posterior vermis and in the cerebellar hemisphere were positively correlated with cells in the inferior olive (r = 0.707 and 0.607, P < 0.05, respectively). Aspartate concentration in the anterior vermis also has a positive correlation coefficient (r = 0.571, 0.05 < P < 0.10) with the density of cells in the inferior olive. GABA concentrations in the dentate nucleus were decreased in all cases of MSA (OPCA) and CCA, and were positively correlated with the degree of loss of Purkinje cells (r = 0.765, P < 0.01). ChAT activities were decreased in certain cases of MSA (OPCA), but conversely, increased in CCA patients. ChAT activity in the posterior vermis has a positive correlation coefficient (r = 0.613, 0.05 < P0.10) with the cell density in the pontine nucleus. A possibility of a compensatory increase of ChAT activity in CCA patients was discussed.

References (23)

L.T. Graham et al.
Fluorometric determination of aspartate, glutamate and γ-aminobutyrate in nerve tissue using enzymic methods
Analyt. Biochem.
(1966)
J.T. Hackett et al.
Glutamate and synaptic depolarization of Purkinje cells evoked by parallel fibers and by climbing fibers
Brain Res.
(1979)
S. Hunt et al.
Some observations on the binding patterns of α-bungarotoxin in the central nervous system of the rat
Brain Res.
(1978)
K.S.K. Kan et al.
Immunohistochemical localization of choline acetyltransferase in rabbit spinal cord and cerebellum
Brain Res.
(1978)
S.J. Kish et al.
Increased GABA receptor binding in dominantly-inherited cerebellar ataxias
Brain Res.
(1983)
E.G. Spokes et al.
Multiple system atrophy with autonomic failure
Clinical, histological and neurochemical observations on four cases
J. Neurol. Sci.
(1979)
A.B. Young et al.
Glutamic acid — Selective depletion by viral induced granule cell loss in hamster cerebellum
Brain Res.
(1974)
K.E. Asin et al.
Regional cerebellar choline acetyltransferase activity following peduncular lesions
Exp. Brain Res.
(1984)
R. Bannister et al.
Degenerative diseases of the nervous system associated with autonomic failure
Brain
(1972)
F. Fonnum
Radiochemical microassays for the determination of choline acetyltransferase and anti-cholinesterase activities
Biochem. J.
(1969)

F. Fonnum

Application of microchemical analysis of subcellular fractionation techniques to the study of neurotransmitters in discrete areas of mammalian brain

Adv. Biochem. Psychopharmacol.

(1972)

Cited by (46)

Gabapentin treatment improves motor coordination in a mice model of progressive ataxia
2009, Brain Research
Citation Excerpt :
GABA content is significantly reduced in HCN1−/− compared to WT mice, such as the expression level of GAD67 mRNA. A reduction in gamma-aminobutyric acid (GABA) content in cerebellar tissue related to the loss of Purkinje cells has been described in cortical cerebellar atrophy (CCA) (Kanazawa et al., 1985). In the mice used in this study, no evident loss of Purkinje cells was observed.
No causal treatment of ataxias is available at the moment, and so symptomatic and disease-modifying therapies are regarded as a reliable possibility for this complex group of movement disorders. In order to explore possible pharmacological strategies aimed at interfering with ataxia development or progression, we used HCN1−/− mice. Mice carrying the deletion of the gene encoding for the voltage-dependent K-channel (HCN1−/−) have a normal basic motor function, but impaired learning of the motor skills that enable mice to balance on the rotating rod. In this study we showed that the motor coordination impairment observed in HCN1−/− mice is paralleled by a decline of GABA content in the cerebellum. Treatment with the GABA mimetic gabapentin at prenatal age prevents full development of the ataxia symptom. This result could have implications for possible therapeutic strategies aimed at more effective coupling with ataxia in several neurological diseases in which this symptom develops and is prominent over time. In view of its long-lasting effect, it could be also considered as a disease-modifying drug.
Reduced brain electric activities of frontal lobe in cortical cerebellar atrophy
2003, Clinical Neurophysiology
Objective: To assess the relationship between cerebellum and brain cortical activity without motor factors, we recorded the mid-latency auditory evoked responses (MLRs) with simultaneous recording of the electroencephalography (EEG) at rest in patients with ‘pure cortical cerebellar atrophy (CCA)’.
Methods: We studied 12 normal control subjects and non-demented ‘pure CCA’ patients determined by quantitative magnetic resonance imaging analysis. A comprehensive neuropsychological test battery assessed intelligence, frontal lobe function and word fluency. Spontaneous eyes-closed resting EEG and MLRs were recorded from 20 scalp electrodes and analysed with low-resolution electromagnetic tomography (LORETA) to compute the 3-dimensional intracerebral distribution of electric activity.
Results: Neuropsychological tests revealed no differences between CCA and the control. Analysis of EEG and MLRs using classical methods also did not reveal any differences. LORETA analysis indicated significant decrease of alpha2 activity in the left inferior frontal gyrus in CCA. On MLRs, the most significant difference was observed at P1 component, and CCA patients showed significant decrease at the right superior frontal gyrus.
Conclusions: Our results indicated that the frontal lobe and ascending reticular activating system are inhibited in CCA patients, and suggested the involvement of the cerebellum in cortical electric activities irrespective of motor adjunct.
Significance: Quantitative EEG and MLR measurements with LORETA pointed out frontal lobe hypoactivities in pure CCA patients.
Myoclonus-dystonia and cerebellar ataxia in association with anti-glutamic acid decarboxylase autoimmunity
2020, Neurologia
Idiopathic Late Onset Cerebellar Ataxia (ILOCA), and Cerebellar Plus Syndrome
2021, Handbook of the Cerebellum and Cerebellar Disorders: Second Edition: Volume 3
Olivopontocerebellar atrophy
2019, Functional Imaging in Movement Disorders
Characteristic diffusion tensor tractography in multiple system atrophy with predominant cerebellar ataxia and cortical cerebellar atrophy
2016, Journal of Neurology

View all citing articles on Scopus

^☆: This work was supported in part by the research grant for the Ataxic Disorders from the Ministry of Health and Welfare of Japan.

View full text

Studies on neurotransmitter markers and neuronal cell density in the cerebellar system in olivopontocerebellar atrophy and cortical cerebellar atrophy☆

Abstract

Analyt. Biochem.

Brain Res.

Brain Res.

Brain Res.

Brain Res.

J. Neurol. Sci.

Brain Res.

Regional cerebellar choline acetyltransferase activity following peduncular lesions

Exp. Brain Res.

Degenerative diseases of the nervous system associated with autonomic failure

Brain

Radiochemical microassays for the determination of choline acetyltransferase and anti-cholinesterase activities

Biochem. J.

Application of microchemical analysis of subcellular fractionation techniques to the study of neurotransmitters in discrete areas of mammalian brain

Adv. Biochem. Psychopharmacol.