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PubMed1995

Localization and pharmacological characterization of somatostatin sst2 sites in the rat cerebellum.

Radioligand binding studies were performed in membranes of rat cerebellum using [125I]-[Tyr3]octreotide ([125I]204-090) to characterize the nature of cerebellar somatostatin receptors. Saturation experiments suggest the presence of a single class of binding sites with high affinity, pKd = 9.53 +/- 0.11, but low receptor density, Bmax = 12.7 +/- 1.0 fmol/mg protein. The pharmacological profile of [125I]204-090 sites in cerebellar membranes was established using a range of ligands known to interact with SSTR-2 (now called sst2) and other somatostatin (SRIF) receptors. SRIF analogues such as octreotide (SMS 201-995), seglitide (MK 678) and somatuline (BIM 23014) displayed very high affinity for cerebellar [125I]204-090 binding sites. The data were compared to results obtained using the same ligand in rat cerebral cortex membranes known to represent sst2 binding. The pharmacological characteristics of the cerebellar sites were in close correlation with those of the cerebral cortex (r = 0.976, n = 19, p < 0.001) and CHO-cells expressing human recombinant sst2 receptor (r = 0.977, n = 19, p < 0.001). By contrast, there was very little correlation between cerebellar binding and published affinities for rat sst5 receptors (r = 0.465), for which octreotide has also high affinity. In vitro autoradiographic studies performed in cerebellar slices using [125I]204-090 demonstrated the presence of binding sites in the molecular layer of the rat cerebellum. In situ hybridization studies using sst2 receptor mRNA selective oligoprobes confirmed the presence of sst2 receptor mRNA in the rat cerebellum. Together, the present data demonstrate the presence of a low density of SRIF receptors in the molecular layer of the adult rat cerebellum which are best characterized as sst2. This is the first pharmacological characterization and localization of sst2 receptors in the adult rat cerebellum.

Amino Acid Sequence↗
PubMed1995

Development of calretinin-immunoreactive unipolar brush-like cells and an afferent pathway to the embryonic and early postnatal mouse cerebellum.

In the developing mouse hindbrain, immunoreactivity for calretinin, a calcium-binding protein, was first observed at embryonic day 10, and was localized to neuronal cell bodies in the reticular formation. By embryonic day 12, fibers emanated rostrally from the calretinin-immunoreactive neurons, extended dorsally and then caudally in the uncinate fasciculus to reach the developing cerebellar plate. These fibers crossed the cerebellar midline and were distributed to the contralateral side of the cerebellum. The number and intensity of staining of cell bodies in the reticular formation was reduced in postnatal mice. After postnatal day 1, it was no longer possible to discern the calretinin-immunoreactive fiber bundle in the brainstem, although fibers were still visible at the level of the uncinate fasciculus and in the cerebellum. We also observed intensely calretinin-immunoreactive, smaller cells in the cerebellum (embryonic day 14) and dorsal cochlear nuclei (embryonic day 18), most of which we believe are destined to become the "unipolar brush", (also known as "pale" or "monodendritic") cells observed in the adult mammalian brain. An immature form of these cells exists in the developing mouse cerebellum. Thus, using calretinin antiserum as a marker, an afferent neuronal system was described which projects to the cerebellar primordium. It is suggested that the calretinin-containing hook bundle is an afferent projection which provides a feed-forward neuronal system to the cerebellum which, in turn, projects afferent fibers to the calretinin-containing and other cells of the reticular formation.

Animals↗
PubMed1996

Bergmann glial development in the mouse cerebellum as revealed by tenascin expression.

Tenascin, an astroglia-derived extracellular matrix molecule, is also expressed by radial glia of the embryonic mouse cerebellum. Expression of tenascin can thus be applied as a marker of astroglial development from an early stage, especially prior to the expression of the glial fibrillary acidic protein (GFAP) that can be detected in the postnatal cerebellum. The development of Bergmann glia, specialized cerebello-cortical astroglia with radial processes, was examined by tenascin immunohistochemistry and non-radioactive in situ hybridization histochemistry for tenascin mRNA in the developing mouse cerebellum. Tenascin-immunopositive radial glial processes extending from the ventricular zone to the pia mater retracted toward the cortex in the embryonic cerebellum and occupied a position corresponding to the Bergmann glial processes at the perinatal stage. Tenascin gene-expressing cells were generated in the ventricular zone of the cerbellar primordium and migrated radially toward the cortex. They were stratified in the layer of Bergmann glial somata at the early postnatal stage. They extended GFAP-immunopositive radial processes from the somata to the pia mater as revealed by double-labeling employing tenascin in situ hybridization histochemistry and GFAP-immunostaining. Bergmann glia are therefore considered to develop from cerebellar radial glia by migration of their somata and retraction of their processes. The tenascin gene-expressing cells displayed mitotic activity after alignment in the cortex as revealed by double-labeling by tenascin in situ hybridization histochemistry and immunohistochemical detection of the incorporated bromodeoxyuridine. The above findings suggest that the Bergmann glia in the cortex represent one of the origins of the astroglia in the developing cerebellum.

Age Factors↗
PubMed1992

Parvalbumin immunoreactive neurons and fibres in the teleost cerebellum.

The distribution of parvalbumin- (PV) immunopositive cell bodies and fibres in the cerebellum of two species of freshwater teleosts (Salmo gairdneri and Barbus meridonalis) was studied using a monoclonal antibody and the avidin-biotin immunoperoxidase technique. A clear laminated pattern of PV immunoreactivity was observed. After PV-immunostaining, Purkinje cells were strongly labelled in their cell bodies, the initial segments of the axons and the dendritic trees. In the molecular layer, only the dendritic branches of the Purkinje cells were PV-positive. In the granule cell layer, extensive axonal plexuses and scattered cell bodies were observed. Most of the immunopositive perikarya were unequivocally identified as displaced Purkinje cells, whereas a reduced number of smaller neurons with unstained dendrites was also found. Eurydendroid cells, the efferent neurons of the teleost cerebellum, were negative; however, they were impinged upon by numerous PV-positive boutons, corresponding to terminals of Purkinje cell axons. Parallel fibres and climbing fibres, as well as stellate cells and granule cells were negative. Basket cells (or deep stellate cells) whose existence in the teleost cerebellum is discussed, were also not observed. The immunoreactivity distribution pattern for PV in the teleost cerebellum differs from previous observations on the localization of this protein in the cerebellum of amniotes.

Animals↗
PubMed1996

Developmental analysis of GFAP immunoreactivity in the cerebellum of the meander tail mutant mouse.

It is thought that Bergmann glial fibers assist in the inward migration of granule cells. Model systems in which there is a perturbation of either the migrating cells or the glial cell population have been useful in understanding the migratory process. In the meander tail mutant mouse, the anterior cerebellar region is agranular, whereas the posterior cerebellum is relatively unaffected by the mutation. This study presents a qualitative analysis of the development of cerebellar radial glia in mea/mea and +/mea mice aged from postnatal day 0 to adult, using an antibody against the glia specific antigen, glial fibrillary acidic protein. The results indicate a slight delay in the onset of immunoreactivity in the mea/mea cerebellum and abnormal glial formation in the anterior and posterior regions by postnatal day 5. At postnatal day 11, the full complement of labeled fibers appears to be present and although they appear abnormal in formation, they eventually reach the surface and terminate in oddly shaped and irregularly spaced endfeet. In adult mea/mea and +/mea mice, as compared to the early postnatal stages, there is a significant reduction in GFAP immunoreactive fibers. Cresyl violet stained adult mea/mea sections revealed the presence of ectopic granule cells in radial columns and small clumps at the surface of and within the molecular layer of the caudal cerebellum. Quantitative analyses revealed a 4- to 5-fold increase in the number of ectopic granule cells in lobule VIII of the mea/mea when compared with the +/mea cerebellum. These results suggest that the radial glia in the mea/mea cerebellum exhibit some uncharacteristic morphologies, but that these abnormalities are most likely the consequence of environmental alterations produced by the mutant gene.

Age Factors↗
PubMed1982

Ultrastructural studies on the ventricular surface of the frog cerebellum.

Ultrastructural studies of the ventricular surface of the frog cerebellum showed regional differences. In the midline region of the adult cerebellum was found a band of profusely ciliated squamous ependymal cells. In the rest of the cerebellum the ependymal cells were columnar and each had a single cilium. In the cerebellum of the premetamorphic tadpole, the squamous ependymal cells of the midline region also were monociliated. During metamorphosis they gradually became multiciliated. Additionally, supraependymal cells and synaptic elements were present on the ventricular surface of the cerebellum of adult frogs as well as in late metamorphic tadpoles. In contrast, supraependymal cells were rarely observed in premetamorphic tadpoles, and it was concluded that the supraependymal system develops during metamorphosis. It is postulated that the band of cilia may be associated with the circulation of cerebrospinal fluid, and supraependymal synaptic elements function in neuroendocrine regulation.

Animals↗
PubMed1982

Enzyme histochemical studies on acid phosphatase in the cerebellum of young Gunn rats.

Cerebella from 20-day-old homozygous (jj) and heterozygous (j+) Gunn rats were tested histochemically for the presence of acid phosphatase. The j+ rat cerebellum as well as the jj rat cerebellum with wet weights over 120 mg showed a strong acid phosphatase activity in the pia mater and in endothelial cells. A strong acid phosphatase activity was also recognized in small cells with a diameter of about 8 micrometers and large cells with a diameter of about 25 micrometers in the hypoplastic cerebellum of jj rats. The small cells were present in the lingula, centralis, culmen, declive, tuber, pyramis, and dorsal part of the uvula of the jj rat cerebellum with wet weight below 120 mg. The large cells were observed only in severely damaged lobes. Neither small cells nor large cells were found in the nodulus even in a cerebellum with a high degree of hypoplasia. Slightly damaged cerebella with wet weight of 100 to 150 mg showed hypoplasia mainly in the anterior lobe including the lingula, centralis, and culmen as well as in the declive and tuber, where no small cells were detected.

Acid Phosphatase↗
PubMed1987

Visuo-motor tracking during reversible inactivation of the cerebellum.

Two monkeys were trained to track a continuously moving target using a joystick. One then had a cooling probe implanted in nucleus interpositus of the cerebellum ipsilateral to his tracking arm. The other had a cannula implanted in the ipsilateral cortex of the lateral cerebellum through which local anaesthetic could be infused. Both monkeys showed similar tracking deficits during temporary inactivation of the cerebellum. The main effects seen were an increase in the peak velocity of their intermittent corrective tracking movements, and a decrease in the accuracy of these movements. Linear regression analyses were undertaken of the peak velocity and amplitude of each corrective movement against a number of possible control signals (target velocity, target position, error, error velocity etc.). The initially strong correlation of the amplitude of each movement made with target velocity was severely reduced during cerebellar inactivation, and movement amplitude became better predicted by the error between target and joystick positions. The peak velocity of movements became more strongly correlated with movement amplitude and less correlated with target velocity than in the intact animal. These results are consistent with the hypothesis that intermittent tracking is achieved by the production of 'primitive' movements, that are then adjusted to the correct amplitude and velocity required to catch up with the moving target. Our findings suggest that the cerebellum may normally be responsible for these adjustments, using visual and memorised cues about the target. The velocity of each movement may be reduced, and its amplitude adjusted, by combining measures of the current error with estimates of target speed and direction. We conclude that the cerebellum has an inhibitory role in tuning movements during visuo-motor tasks and that optimal tuning using feedforward measurements of target motion cannot be made without it.

Anesthesia, Local↗
PubMed1978

On the development of the cerebellum of the trout, Salmo gairdneri. I. Patterns of cell migration.

Patterns of cell migration in the cerebellum of Salmo gairneri RICHARDSON, 1836 were studied in fish ranging in length from 4.5 to 230 mm. Sagittal and transverse series were stained with haematoxylin-eosin or according to Nissl or Golgi. The cerebellum of the trout comprises three main parts, i.e. the massive corpus cerebelli, the folded valvula cerebelli and the transversely oriented lobus vestibulolateralis. The early cerebellar anlage is a simple plate, which is delimited from the tectum mesencephali by the fissura rhombo-mesencephalica. The histogenesis may be divided into three phases. During the first phase the matrix layer produces the mantle layer. During the second phase the three typical cerebellar layers are formed. The third phase is characterized by growth. As regards the first phase, the mantle layer develops throughout almost the entire extent of the cerebellar anlage. Only in a narrow paramedian strip (matrix zone M) this layer does fail to appear. In regions where the mantle layer is formed, the matrix no longer occupies the whole width of the wall and is termed the ventricular matrix. The largest part of the ventricular matrix is gradually exhausted. However, in some places this matrix persists as a layer of proliferating cells. This holds for the matrices of the caudal border of the cerebellum; matrix zone L, surrounding the lateral recesses of the fourth ventricle, and matrix zone P, connecting the matrix zones L. The mantle layer produced in the first phase of histogensis mainly develops into the ganglionic layer. The second phase of histogenesis is characterized by the formation of a secondary matrix. Newly produced cells of the matrix zones M, L and P migrate away from their sites of origin towards the regions where a mantle layer prevsiously has been formed. The majority of these cells develops into granule cells. Migration of the cells produced in the first phase of histogenesis occurs in the radial direction. Because of the curvature of the cerebellum this direction changes with respect to the main longitudinal axis of the brain from region to region. The migration paths of granule cells show variable directions, namely (a) tangential followed by radial, for granule cells in the corpus cerebelli and in the medial parts of the valvula cerebelli and the lobus vestibulolaterialis, (b) tangential, for granule cells in the lateral parts of the valvula and (c) radial, for granule cells in the lateral parts of the lobus vestibulolateralis. The analysis of these migration patterns elucidates both the histogenesis and the morphogenesis of the cerebellum of the trout.

Animals↗
PubMed2005

Binding kinetics of 11C-N-methyl piperidyl benzilate (11C-NMPB) in a rhesus monkey brain using the cerebellum as a reference region.

The binding kinetics of 11C-N-methyl piperidyl benzilate (11C-NMPB) in rhesus monkey brain were studied using animal positron emission tomography (PET) (SHR2000). This study is intended to assess the validity of the method using the cerebellum as a reference region, and to evaluate the effects of anesthesia on 11C-NMPB binding. Two monkeys, anesthetized with ketamine, received intravenous 11C-NMPB alone (370-760 MBq, < 1 microg/kg) or mixed with varying doses of nonradioactive NMPB (3 microg/kg, 10 microg/kg, 30 microg/kg) and were subjected to PET scans for 60 minutes. Regions of interest (ROI) were drawn on reconstructed PET images and a time-activity curve was obtained for each region. 11C-NMPB accumulated densely in the striatum and cerebral cortex with time. In contrast, the tracer accumulation significantly decreased with increased doses of nonradioactive NMPB. In the cerebellum, on the other hand, the accumulation of 11C-NMPB remained low and the tracer was slowly eliminated from the brain following the injection. 11C-NMPB binding in the cerebellum was barely affected by the increased dose of nonradioactive NMPB. We thus concluded that the specific 11C-NMPB binding was negligible in the cerebellum, and performed simplified evaluation of 11C-NMPB binding in each brain region by a graphical method using the cerebellum as a reference region. PET was conducted 26 times, in total both in ketamine-anesthetized and awake monkeys (n = 3 each). Measurements of 11C-NMPB binding showed good run-to-run reproducibility within individual animals. When 11C-NMPB binding was compared between ketamine-treated and awake animals, a significant increase in 11C-NMPB binding was observed in the striatum but not in other brain regions of ketamine-treated animals.

Animals↗
PubMed2006

Structural and functional alterations of cerebellum following fluid percussion injury in rats.

Cerebellum was shown to be vulnerable to traumatic brain injury (TBI) in experimental animals. However, the detailed pathological and functional changes within the cerebellum following TBI are not known. Using our established cerebellum fluid percussion injury (FPI) model, we characterized the temporal pattern and the nature of structural damage following FPI, as well as the functional changes of Purkinje cells in response to climbing fiber activation. Our results showed that 60% of Purkinje cells died within the first 24 h following moderate FPI. In contrast, clusters of densely stained shrunken granule cells were stained positive for terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL) in 1, 3 or 7 days following FPI animals. We also observed an accompanying structural damage to the cerebellar white matter tract. Disconnected axonal fibers appeared 1 day post-FPI, and loss of white matter fibers were visible 3 and 7 days post-FPI. Massive accumulation of beta-amyloid precursor protein (betaAPP) was found in the white matter tracts and molecular layer in the cerebellum of 1, 3 or 7 days FPI animals. Our functional study showed that the majority of Purkinje cells from 1 day and all cells from 3 to 7 days post-FPI had distorted membrane potential and synaptic responses to climbing fiber activation. These results suggested that there is a co-related structural and functional deterioration with a specific temporal pattern in the cerebellum following FPI. These observations provide a basis for future mechanistic investigations aiming to realize neuroprotection from cerebellar neuronal death and loss of cerebellar functionality.

Amyloid beta-Peptides↗
PubMed2004

Occurrence of alpha-synuclein pathology in the cerebellum of Guamanian patients with parkinsonism-dementia complex.

Amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a progressive neurodegenerative disease affecting the indigenous Chamorro population of Guam. Neuropathologically, PDC is characterized by neuronal loss in the substantia nigra pars compacta with severe widespread neurofibrillary tangles (NFTs) similar to those observed in Alzheimer's disease (AD), and is thus considered a tauopathy. Following reports of alpha-synuclein pathology in PDC patients of Guam, PDC has also been neuropathologically classified as a synucleinopathy. Recently, the presence of alpha-synuclein-positive bodies has been reported in the cerebellum of some patients with Parkinson's disease (PD), diffuse Lewy body disease (DLBD), or multiple system atrophy (MSA). Using immunohistochemical techniques, we investigated the deposition of alpha-synuclein in the cerebellum of Guamanian PDC patients. Numerous alpha-synuclein-immunoreactive spherical structures were found in the molecular layer of the cerebellum of 63.6% of PDC patients. These structures were only seen in patients showing alpha-synuclein pathology in the amygdala. The average density of alpha-synuclein-immunoreactive structures in the cerebellum of Guamanian PDC patients was almost an order of magnitude higher than in non-Guamanian PD patients, and this alpha-synuclein pathology was much more pronounced in the hemisphere than in the vermis. In addition, double immunohistochemistry revealed that cerebellar alpha-synuclein is co-localized with the neuronal marker calbindin and with glial-fibrillary acidic protein, suggesting the involvement of Purkinje cells and Bergmann glia. These findings demonstrate that the alpha-synuclein pathology in PDC of Guam affects not only the amygdala, but also the cerebellum, where it appears to involve both Purkinje cells and specialized astrocytes.

Aged↗
PubMed2003

Development and developmental disorders of the human cerebellum.

The human cerebellum develops over a long time, extending from the early embryonic period until the first postnatal years. This protracted development makes the cerebellum vulnerable to a broad spectrum of developmental disorders. The development of the cerebellum occurs in four basic steps: 1) characterization of the cerebellar territory at the midbrain-hindbrain boundary; 2) formation of two compartments for cell proliferation: first, the Purkinje cells and the deep cerebellar nuclei arise from the ventricular zone of the metencephalic alar plate; second, granule cell precursors are formed from a second compartment of proliferation, i. e. the upper rhombic lip; 3) inward migration of the granule cells: granule precursor cells form the external granular layer, from which (and continuing into the first postnatal year), granule cells migrate inwards to their definite position in the internal granular layer, and 4) formation of cerebellar circuitry and further differentiation. The precerebellar nuclei, i. e. the pontine nuclei and the inferior olive, arise from the lower rhombic lip. Developmental disorders of the cerebellum are often accompanied by malformations of the precerebellar nuclei. In this review the development of the cerebellum and some of its more frequent developmental disorders, such as the Dandy-Walker and related midline malformations, and the pontocerebellar hypoplasias, are discussed.

Cerebellar Diseases↗
PubMed2003

Immunolocalization of the acid-sensing ion channel 2a in the rat cerebellum.

The acid-sensing ion channels (ASICs) are members of the DEG/ENaC superfamily of Na+ channels. Acid-gated cation currents have been detected in neurons from multiple regions of the brain including the cerebellum, but little is known about their molecular identity and function. Recently, one of ASICs (ASIC1a) was implicated in synaptic plasticity. In this study we examined the subcellular distribution of ASIC2a in rat cerebellum by immunostaining and confocal microscopy. Monoclonal antibodies for labeling of defined brain structures, for example, astroglia, Purkinje cell dendrites, nuclei, and presynaptic terminals were used for colocalization analyses. In the gray matter, the anti-ASIC2a antibody intensively stained dendrite branches of Purkinje cells evenly distributed throughout the entire molecular layer (ML). In the granule cell layer (GL), anti-ASIC2a antibody stained synaptic glomeruli. Neuronal localization of ASIC2a was confirmed by lack of co-staining with glial fibrillary acidic protein. Anti-ASIC2a staining in the ML colocalized with metabotropic glutamate receptor 1alpha (mGluR1alpha) in Purkinje cell dendrites and dendritic spines. Both proteins, mGluR1alpha and ASIC2a, were enriched in a crude synaptic membrane fraction prepared from cerebellum, suggesting synaptic expression of these proteins. Dual staining with anti-syntaxin 1A and anti-ASIC2a antibodies demonstrates characteristic complementary distribution of two proteins in both ML and GL. Because syntaxin 1A localized in presynaptic membranes and synaptic vesicles, complementary distribution with ASIC2a suggests postsynaptic localization of ASIC2a in these structures. This study shows specific localization of ASIC2a in both Purkinje and granule cell dendrites of the cerebellum and enrichment of ASIC2a in a crude cerebellar synaptic membrane fraction. The study is the first report of synaptic localization of ASIC2a in the CNS. The synaptic localization of ASIC2a in the cerebellum makes this channel a candidate for a role in motor coordination and learning.

Acid Sensing Ion Channels↗
PubMed2006

Developmental changes in the expression pattern of the JNK activator kinase MUK/DLK/ZPK and active JNK in the mouse cerebellum.

JNK is one of the key molecules regulating cell differentiation and migration in a variety of cell types, including cerebral cortical neurons. MUK/DLK/ZPK belongs to the MAP kinase-kinase-kinase class of protein kinases for the JNK pathway and is expressed predominantly in neural tissue. We have determined the expression pattern of MUK/DLK/ZPK and active JNK in the cerebellum at different stages of postnatal development. Quantitative analysis by Western blotting has showed that high expression levels of MUK/DLK/ZPK and active JNK are maintained during the postnatal development of the cerebellum, and that these levels decrease in the adult cerebellum. Immunohistochemical staining has revealed, however, that their distribution in the developing cerebellum is considerably different. Although active JNK is highly concentrated in the premigratory zone of the external germinal layer (EGL), high expression of MUK/DLK/ZPK has been observed in the molecular layer and in the premigratory zone. Neither the active JNK nor MUK protein has been detected in the proliferative zone of the EGL. These observations suggest that during the postnatal development of the cerebellum, the MUK-JNK signaling pathway contributes to the regulation of granule cell differentiation and migration; further, the activity of MUK/DLK/ZPK is tightly regulated by posttranslational mechanisms and by its expression level.

Animals↗
PubMed2003

Activation of cerebellum and basal ganglia on volitional swallowing detected by functional magnetic resonance imaging.

Although regions of the sensorimotor cortex, insula, and anterior cingulate gyrus are reported to be activated during swallowing, findings concerning contributions of the cerebellum and basal ganglia have been contradictory. We investigated cerebellar and basal ganglionic activation using functional magnetic resonance imaging (fMRI). In 11 subjects, single-shot gradient-echo echoplanar image volumes sensitive to BOLD contrast were acquired in block design fashion using an oblique orientation covering both cerebrum and cerebellum. Using statistical parametric mapping, regional activation upon swallowing was observed in the sensorimotor cortex, insula, cerebellum, putamen, globus pallidus, thalamus, anterior cingulate gyrus, supplementary motor area, superior temporal gyrus, and substancia nigra. The cerebellum was activated bilaterally, especially on the left; activation of the putamen and globus pallidus was also found bilaterally. Thus, volitional swallowing involves the cerebellum and basal ganglia as well as cortical structures. The method used was well tolerated by normal subjects and should also be applicable to patients with dysphagia.

Adult↗
PubMed1977

Impairment of DNA synthesis in Gunn rat cerebellum.

Brain DNA synthesis was developmentally investigated in Gunn rat with marked cerebellar hypoplasia due to hereditary hyperbilirubinemia. In this mutant rat, the Purkinje cell was nearly selectively affected in the cerebellar cortex by bilirubin. The impaired DNA synthesis was observed in homozygous (jj) Gunn rat cerebellum, in which the DNA content and [3H]thymidine incorporation rate into DNA decreased after 10 days of age compared to those in the heterozygous (Jj)littermate. In contrast, these impairments were not found in the non-cerebellar parts of the brain and liver of jj Gunn rat. The activity of cerebellar thymidine kinase in jj Gunn rat decreased from a very early stae, being 80% of Jj rat at 6 days, and 50% at 10 days of age. The enzyme activity was not affected in the non-cerebellar parts of the brain. Although bilirubin competitively inhibited cerebellar thymidine kinase activity in vitro (15% at 10(-5) M), such bilirubin level was found to be about 1000-fold that in vivo. Moreover, photo-degradation of bilirubin in jj cerebellum exhibited no improvement in thymidine kinase activity, and the presence of an enzyme inactivator was not suggested in jj cerebellum. These results seem to indicate that the induction of thymidine kinase might be affected in jj Gunn rat cerebellum. The possibility that the impaired DNA synthesis in the external granular cells in jj cerebellum may be due to Purkinje cell damage is discussed.

Animals↗
PubMed1978

A chemical study on the development of the human forebrain and cerebellum during the brain 'growth spurt' period. I. Gangliosides and plasmalogens.

Following upon previous studies on the lipid composition of the developing human brain, a further study is presented with the main object of tracing the chemical changes underlying the period of brain 'growth spurt'. Gangliosides and plasmalogens were selected as approximate markers of synaptogenesis and myelination, respectively, and these lipids were compared in cerebrum and cerebellum to establish the time, if any, at which their rate of accretion increases in a significant way. In the forebrain the rate of increase in concentration of these lipids accelerated at about the 32nd week of gestational age. Although there were too few postnatal cases to draw very firm conclusions, it seemed that the ganglioside concentration levelled off at about two months postnatal age and that the plasmalogen concentration reached a plateau between the 4th and the 6th postnatal months. In the cerebellum the concentration of gangliosides was clearly lower than that in the forebrain until about one year of age, the maximum rate of increase occurring between the last weeks of gestation and the second postnatal month. The plasmalogen concentration was somewhat higher in the cerebellum than in the forebrain but the concentration profile was similar to that followed by the gangliosides. In clear contrast with the concentration profiles in the cerebrum, in the cerebellum both lipids apparently continued to increase up to the second postnatal year. A mainly perinatal period of vulnerability is suggested for the forebrain, and a more prolonged one (probably until the second year of life) for the cerebellum.

Cerebellum↗