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PubMed2005

Cognitive and emotional functions of the teleost fish cerebellum.

Increasing experimental and neuropsychological evidence indicates that the cerebellum of humans and other mammals, traditionally associated with motor control, is implicated in a variety of cognitive and emotional functions. For example, the cerebellum has been identified as an essential structure in different learning processes, ranging from simple forms of associative, sensory-motor learning and emotional conditioning, to more complex, higher-order processes such as spatial cognition. Although neuroanatomical and neurophysiological data indicate that the organization of the cerebellum is notably well conserved in vertebrates, little is actually known about the cerebellar contribution to processes besides the motor domain in non-mammals. In this work, we analyzed the involvement of the teleost fish cerebellum on classical conditioning of motor and emotional responses and on spatial cognition. Cerebellum lesions in goldfish impair the classical conditioning of a simple eye-retraction response analogous to the eyeblink conditioning described in mammals. Single unit extracellular electrophysiological recording and cytochrome oxidase histochemistry also reveal the involvement of the teleost fish cerebellum in classical conditioning. Autonomic emotional responses (e.g., heart rate classical conditioning) are also impaired by cerebellum lesions in goldfish. Furthermore, goldfish with cerebellum lesions present a severe impairment in spatial cognition. In contrast, cerebellum lesions do not produce any observable motor deficit as indicated by the swimming activity or obstacle avoidance and do not interfere with the occurrence of unconditioned motor or emotional responses. These data indicate that the functional involvement of the teleost cerebellum in learning and memory is strikingly similar to mammals and suggest that the cognitive and emotional functions of the cerebellum may have evolved early in vertebrate evolution, having been conserved along the phylogenetic history of the extant vertebrate groups.

Animals↗
PubMed2002

Neural network models for the gaze shift system in the superior colliculus and cerebellum.

We investigate the role that the superior colliculus (SC) and the cerebellum might play in generating gaze shifts. The discharge of cells in the intermediate layers of the SC is tightly linked to the occurrence of saccades. Many studies have demonstrated that the cerebellum is involved in both eye and head movements. When the head is unrestrained, large amplitude gaze shifts are composed of coordinated eye and head movements. In this study, we propose that the gaze saccades system is controlled by a feedback loop between the SC and the cerebellum. The SC only encodes retinal coordinates and controls the eye displacement (to move the fovea to the target), while the cerebellum deals with the gaze programming and controls the head displacement. When a target appears in space, the buildup cells within the SC decode the target signal in the retina before the saccade onset, and input the signal of the gaze displacement to the cerebellum. The cells in the cerebellum vermis encode the initial position of the eye in the orbit. The gaze displacement is decomposed into the head amplitude and the eye amplitude within the cerebellum. There are two output signals from the cerebellum. One signal controls the head movement. The other is projected back to the SC, and forms a component of the saccade vector to control the eye movement. The sum of the vectors provided by the cerebellum and the vector provided by the burst cells in the SC indicates the direction and the amplitude of the desired movement of the eye during the saccade. We propose a cerebellum model to predict the displacements of the eye and head under the condition that the position of the target signal in the retina and the initial position of the eye in the orbit are known. The results from the model are close to that observed physiologically. We conclude that before gaze shift onset, the cerebellum may play an important role in decomposing the gaze displacement into an eye amplitude and head amplitude signal.

Animals↗
PubMed2000

Revised T3 uptake and T4-to-T3 conversion in brain and cerebellum of 10-day-old rats: a compartment analysis.

The peripheral and cerebral metabolism of thyroid hormones in 10-day-old rats was evaluated by measuring the kinetics of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) fluxes. Labeled iodo-compounds were measured in the plasma, cerebellum and brain (without cerebellum) for 24 hours after the intravenous injection of [125I]T4 plus [131I]T3. Data were interpreted by compartment analysis. T4 was produced at 8.93 pmol x h(-1) and T3 at 2.26 pmol x h(-1) for 22.7 g body weight. The T4 and T3 distribution volumes were 4.26 and 22.7 ml, whereas the extra-cellular fluid volume was 9.42 ml. T4 was therefore considered to be mostly extra-cellular and T3 mostly intracellular. This was confirmed in the brain and cerebellum, where the extra-cellular fluid (ECF) fraction was 0.021 ml/g organ and the tissue-to-plasma ratio of labeled and endogenous hormones was 0.54-6.54 ml plasma/g tissue for T3 and 0.048-0.136 ml plasma/g tissue for T4. The T3 in the brain and cerebellum was distributed in several pools. The first, representing 11% of the cerebellum and 8% of the brain (without cerebellum) T3, was quickly exchanged with circulating T3. The second pool, derived from the local T4 5'-deiodination, represented 48% of the cerebellum and 94% of the brain (without cerebellum) hormone; a possible third pool (41% of the hormonal content) in the cerebellum appeared to be unlabeled by radioactive T3, and motionless. The in vivo T4 to T3 conversion, as a function of weight, accounted for 21% of cerebellum needs and 43% of brain needs. The rest was provided by T3 uptake.

Animals↗
PubMed1984

Evidence that a cerebellum-enriched, synaptic junction glycoprotein is related to fodrin and resists extraction with triton in a calcium-dependent manner.

Subcellular fractions from rat cerebellum and other tissues were examined for the presence of a 240K glycoprotein, designated GP-A. Previous results have shown that GP-A is enriched in cerebellum synaptic junction (SJ) fractions when compared to parent synaptic plasma membrane (SPM) fractions and is not detected in forebrain SPM or SJ fractions. In the present studies, GP-A was not detected in myelin, mitochondria, purified nuclei, or cytosolic fractions from cerebellum, but was present in microsomal fractions. GP-A is partially soluble in the non-ionic detergent Triton X-100 and is completely soluble when cerebellum SPMs are treated with the ionic detergent N-lauryl sarcosinate. The solubilization of GP-A from cerebellum membranes was shown to be a function of bound calcium ions, e.g., pretreating SPMs with 100 microM-1mM Ca2+ decreased the solubility of GP-A in Triton by approximately threefold. GP-A is a major concanavalin A (Con A)-binding glycoprotein in cerebellum SJ fractions and migrates on sodium dodecyl sulfate (SDS) gels with a slower relative mobility than the 235K/230K fodrin doublet. Comparisons between purified fodrin and the 235K/230K doublet in cerebellum and forebrain synaptic fractions by two-dimensional peptide mapping indicated that they were identical. The Con A-binding property of GP-A was exploited to purify it by affinity chromatography with agarose-Con A. Peptide mapping comparisons between affinity-purified GP-A and GP-A in SPM and SJ fractions indicated that GP-A in synaptic fractions is apparently homogeneous. Peptide map comparisons between GP-A and 235K fodrin poly-peptide indicated that these two synaptic components are highly related (50% of their respective peptides are shared). The 235K fodrin polypeptide in SJs reacted with anti-fodrin antisera on Western blots; however, GP-A failed to cross-react. These observations, together with results from previous studies, indicate that GP-A is highly enriched in cerebellum compared to other neuronal and nonneural tissues. Moreover, GP-A is enriched in SJs relative to SPM fractions, is related to fodrin, and is most likely a cell-surface glycoprotein at asymmetric synapses in cerebellum. GP-A may be involved in neuronal recognition or synaptic transmission in the cerebellum. The important role of calcium in synaptic transmission, together with the decreased solubility of GP-A in Triton that results from micromolar concentrations of calcium, suggest that GP-A may play a role in stabilizing cerebellar synaptic junctions.

Animals↗
PubMed2003

Dose- and duration-dependent alterations by tellurium on lipid levels: differential effects in cerebrum, cerebellum, and brain stem of mice.

The effect of various doses of sodium tellurite (1/50 LD50=0.4 mg/kg, 1/25 LD50=0.8 mg/kg, and 1/10 LD50=2.0 mg/kg body weight orally) on the lipid levels (cholesterol, triglycerides, phospholipids, esterified fatty acids, gangliosides, and total lipids) in the cerebrum, cerebellum, and brainstem of male albino mice was studied after 7 and 15 d of treatment. Sodium tellurite (2.0 mg/kg body weight) for 7 d has an apparent effect on the depletion of cholesterol, triglycerides, phospholipids, esterified fatty acids, and total lipids. The cholesterol content was decreased significantly in the cerebrum, cerebellum, and brainstem after 7 d of treatment with a 2.0-mg/kg dose compared to the control. On the other hand, treatment for 15 d with doses of 0.4, 0.8, and 2.0 mg/kg body weight resulted in a significant and dose-dependent increment in cholesterol level in the cerebrum, cerebellum, and brainstem. The triglycerides content was decreased significantly in the cerebrum, cerebellum, and brainstem with the 2.0-mg/kg dose after 7 d of treatment. The doses of 0.4, 0.8, and 2.0 mg/kg orally for 15 d resulted in a significant and dose-dependent depletion of triglycerides in the cerebrum, cerebellum, and brainstem. All the doses of tellurium (0.4, 0.8, and 2.0 mg/kg) both for 7 and 15 d have depleted the level of phospholipids in varying degrees of significance in the cerebrum, cerebellum, and brainstem. However, the level of esterified fatty acids was decreased significantly with the 2.0-mg/kg dose of tellurium for 7 d but increased with the 0.4-mg/kg dose for 15 d in the cerebrum and cerebellum. The level of gangliosides was depleted in the cerebrum but elevated in the cerebellum and brainstem after receiving a 2.0-mg/kg dose of sodium tellurite for 7 d. The content of gangliosides was increased with doses of 0.4 and 0.8 mg/kg but decreased with 2.0 mg/kg for 15 d in the cerebrum, cerebellum, and brainstem. The total lipids content was depleted significantly and dose dependently after 7 and 15 d of treatment in the cerebrum, cerebellum, and brainstem. These results suggest that sodium tellurite affects the lipids content differentially in various parts of the mice brain.

Animals↗
PubMed2005

Afferent projections from motoneurons innervating extraocular muscles to the cerebellum demonstrated by the retrograde double-labeling technique.

The objective of this study was to investigate the characteristics and distributions of neuronal origin of cerebellar afferents from motor cranial nerve nuclei innervating extraocular muscles by the method of retrograde transport of two fluorescence tracers in rats. Under deep anesthesia and aseptic conditions, 5 microl of 3% solution of Fluoro-Gold (FG) in phosphate buffer solution (PBS) was injected into the bellies of the six extraocular muscles to study the labeling of motoneurons innervating corresponding extraocular muscles. The cerebellum was exposed by craniotomy, and 0.3 microl of 10% solution of Dextran Tetramethyl Rhodamine Biotin (Micro Ruby: or MR) in PBS was injected into many regions of the anterior vermis (lobule I, II) and the posterior vermis (lobule VI, VII, IX, X), the flocculus, the paraflocculus and the deep cerebellar nuclei. Multiple injections were made to cover the entire cerebellum in order to obtain a near maximum labeling of cerebellar afferent neurons. In other cases, only small single or a few injections were made in specific areas of the cerebellum to study specific distributions and topographic organization. In one group of rats, injections were made both in the extraocular muscles with FG and in the cerebellum with MR to study the double labeling of neurons, which project their axons to both the extraocular muscle and the cerebellum. Another group of rats were injected in both sites with only PBS and served as the control for auto-fluorescence background. After 3 days postoperative survival time, all animals were deeply reanesthetized and perfused with heparinized normal saline solution, followed by 4% paraformaldehyde in 0.1 M phosphate buffer, pH 7.4, and 30% sucrose solution in PBS. The brainstem and the cerebellum were removed immediately, and stored in sucrose solution in PBS at 4 degrees C. Serial transverse sections of the brainstem and sagittal sections of the cerebellum were obtained by a freezing microtome at 40 microm thickness, collected on uncoated glass slides, and immediately dried. All sections were examined under an epifluorescence or confocal microscope equipped with filter systems for FG and MR. The presence of both single and double retrograde labeled neurons in the Oculomotor (CN 3), Trochlear (CN 4) and Abducens (CN 6) nuclei was recorded, photographed, stored as computer images files and printed out as hard copies. The labeling neurons in the vicinity of the CN 3, 4, 6 from all sections were plotted onto diagrams and counted Neurons labeled only with MR retrogradely transported from injection sites in the cerebellum were found bilaterally and scattered throughout in the Oculomotor, Trochlear and Abducens nuclei. These neurons labeled only with MR were small and medium-sized interneurons and represented only a small proportion of the entire population. Neurons labeled only with FG retrogradely transported from injection sites in the extraocular muscles were the most numerous, and distributed almost throughout the entire population of small, medium-sized and large motoneurons, which innervate the extraocular muscles. A smaller proportion of small and medium-sized FG labeled neurons within these nuclei were also double labeled with MR, indicating that they project their axon collaterals to both extraocular muscles and the cerebellum. In conclusion, the present findings provide clear anatomical evidence that a small population of motoneurons in the Oculomotor, Trochlear and Abducens nuclei of the rat project their axon collaterals directly to the cerebellum and the extraocular muscle, in addition to the cerebellar afferents from other interneurons within these nuclei. The findings also indicate that cerebellar neuronal circuits play more direct roles in monitoring and controlling eye movements than previously known.

Afferent Pathways↗
PubMed1984

Architectonic and hodological organization of the cerebellum in reeler mutant mice.

The architectonic and hodologic organization of the reeler cerebellum has been studied by means of immunohistochemistry, general cell and fiber stains and by horseradish peroxidase and autoradiographic tracing methods. Malposition of Purkinje cells, which varies in degree, is the most salient architectonic anomaly of the mutant cerebellum. Mapping the distribution of Purkinje cells is facilitated by a monoclonal antibody which selectively stains neurons of this class in the cerebellum. Although some Purkinje cells form a normal monolayer, most lie in heterotopic positions within or below the granule cell layer. The major contingent is segregated in subcortical masses in the depths of the cerebellum. Fiber bundles continuous with the cerebellar peduncles run in septa between the subcortical Purkinje cell masses. The distribution of Purkinje cell masses as well as the roof nuclei and areas of normal cortex and fiber bundles are identical from animal to animal. These consistent architectonic variations serve to partition the reeler cerebellum into 7 sagittally oriented compartments: one medial, two intermediate, two lateral and two additional lateral lobular appendages which may correspond to paraflocculus and/or flocculus of the normal cerebellum. The topography of the reeler olivocerebellar, or climbing fiber, system is normal in that the caudal-to-rostral axis of the olivary complex maps onto the medial-to-lateral axis of the contralateral hemicerebellum. The climbing fiber projection in reeler, like that of the normal animal, appears to be organized in parasagittal strips. In the mutant, mossy fibers from the pons and spinal cord project respectively to the lateral and medial cerebellar fields, and overlap in the intermediate compartment. They thus invest different and to a large extent complementary cerebellar territories, which approximate the architectonic divisions. This segregation of the two principal mossy fiber systems is not so marked in the normal cerebellum. In terms of laminar distribution, the pontine projection is distributed principally to the granule cell stratum in the mutant. The reeler spinocerebellar afferents, by contrast, project not only to the granule cell layer but also to the heterotopic Purkinje cells. The present observations suggest that the primary defect in the reeler cerebellum is malposition of Purkinje cells. As appears to be the case during development of the forebrain in reeler, the mutation may affect the terminal phase of migration of Purkinje cells in the cerebellum.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2004

Cadherin-2 and cadherin-4 in developing, adult and regenerating zebrafish cerebellum.

Cadherins are cell adhesion molecules that regulate development of a variety of tissues and maintenance of adult structures. In this study, we examined expression of two zebrafish classical cadherins, cadherin-2 and cadherin-4, in the cerebellum of developing, normal adult, and regenerating adult zebrafish using in situ hybridization and immunohistochemical methods. Cadherin-2 was widely expressed by the cerebellum of embryonic (24-50-h post fertilization) and larval zebrafish (3-14 days). Cadherin-2 expression became much reduced in the adult cerebellum, but it was greatly up-regulated in the regenerating adult cerebellum. Cadherin-4 was not detected in the embryonic cerebellum, but it was expressed in the Purkinje cells of the larval and adult cerebellum. To gain insight into cadherin-2 role in the formation of the cerebellum, we analyzed embryos injected with a specific cadherin-2 antisense morpholino oligonucleotide (cdh2MO1), and found that the cerebellar development of the cdh2MO1-injected embryos was severely disrupted. This phenotype was confirmed by examining a cadherin-2 mutant, glass onion. Our results suggest that cadherins are crucial for the normal development of the zebrafish cerebellum, and they may also be involved in the regeneration of injured fish cerebellum.

Animals↗
PubMed2000

Mechanisms of motor learning in the cerebellum.

How the elaborate neuronal circuit in the cerebellum operates and is involved in motor learning is a question addressed in earnest in studies on the cerebellum. During the past four decades, experimental studies have revealed circuit and module structures of the cerebellum, established long-term depression (LTD) as a unique and characteristic type of synaptic plasticity in the cerebellum, and analysed signal contents of activates of cerebellar neurons related to motor learning. In the 1990s, these studies were developed to detailed analyses of the signal transduction underlying LTD, and to uncovering the involvement of the cerebellum in cognitive function. On the other hand, theoretical studies yielded epochal Marr-Albus network models of the cerebellum around 1970, and introduced control system principles explaining the essential roles of the cerebellum in motor learning as providing internal models, both forward and inverse. The author maintains the hypothesis that reorganisation of the neuronal circuit by error-driven induction of LTD constitutes the major memory and learning mechanisms of the cerebellum. In this article, we examine the validity of the hypothesis in light of currently available data in recent studies of the cerebellum.

Animals↗
PubMed2002

Evolution of cerebellum-like structures.

All vertebrate brains have a cerebellum, and most of them have one or more additional structures that are histologically similar to the cerebellum. The cerebellum-like structures include the medial octavolateral nucleus in most aquatic vertebrates; the dorsal octavolateral nucleus in many aquatic vertebrates with an electrosensory system; the marginal layer of the optic tectum in ray-finned fishes; electrosensory lobes in the few groups of advanced bony fish with an electrosensory system; the rostrolateral nucleus of the thalamus in a few widely scattered groups of bony fish; and the dorsal cochlear nucleus in all mammals except monotremes. All of these structures receive topographically organized sensory input in their deep layers. Purkinje-like cells receive the sensory input near their cell bodies. These cells extend apical dendrites up into the molecular layer where they receive synaptic input from parallel fibers. The cerebellum itself can be included within this characterization by considering the climbing fiber as at least in part a conveyor of sensory information and by recalling that climbing fibers in more basal vertebrates terminate on smooth dendrites close to the soma. Physiological findings from three different systems suggest the hypothesis that cerebellum-like structures remove predictable features from the sensory inflow. Phylogenetic homology can explain the similarities across different taxa for some types of cerebellum-like structures, but similarities within other types cannot be explained in this way. Moreover, phylogenetic homology cannot explain the similarities among different types of cerebellum-like structures. Evolutionary convergence provides the best explanation for all these similarities that cannot be explained by homology. The convergence is almost surely constrained by the availability of a genetic-developmental program for creating cerebellum-like circuitry and by the need within many different systems for the type of information processing that cerebellum-like circuitry can provide.

Animals↗
PubMed2002

[The cerebellum: anatomy, distribution of mediators and their receptors, communication with hypothalamic structures and comparison with the hypothalamic paraventricular nucleus under conditions of stress].

Cerebellum is a profound structure of the central nervous system. Human cerebellum weighs about 150 g which represents around 10% of the total weight of the brain. It receives main input from sensory systems but the cerebellum functions as a part of the motor system. The cerebellum contributes by only few direct connections to motoneurons (therefore it cannot initiate any motor activity) but it projects profusely to all major motor control regions of the cerebral cortex. The cerebellum acts as a controller and coordinator. It compares movement intention with, performance and coordinates the equilibrium, posture and muscle tone necessary for the smooth coordinated motor activity. The number of input projections which exceed considerably the output ones (40:1) speaks out of an enormous analytical and synthetic capacity of the cerebellum. Interneuronal transmission of informations and carriage of afferent and efferent signals are provided by wide variety of chemical messengers (amino acids, biogenic amines and neuropeptides) of the local origin or delivered from the precerebellar nuclei. Direct and reciprocal connections between the hypothalamus and cerebellum have anatomically been well documented but monosynaptic contacts between the cerebellum and the hypothalamic paraventricular nucleus have not been approved yet. Cerebellum can respond to stress, however, this response may not be related only to the primary effect of the stressor but also to its consequences.

Afferent Pathways↗
PubMed1991

Nerve growth factor receptor immunoreactivity in the new world monkey (Cebus apella) and human cerebellum.

The present study used the NGFR-5 monoclonal antibody raised against human nerve growth factor receptor (NGFR) to determine the extent of NGFR immunoreactivity within the embryonic and young adult Cebus apella cerebellum as well as the human cerebellum. Immunohistochemically processed tissue revealed NGFR expressing Purkinje cell somata, axons, and dendrites, the latter being observed within the molecular layer of both adult species. Within all regions of the cerebellum we observed both darkly and lightly immunostained Purkinje cells. The proximal axons of these cells, which were visualized for short distances within the granular cell layer, appeared to contain bulbous aggregates of reaction product. In sagittal sections, the full extent of the Purkinje cell dendritic tree was observed in the more lightly stained portions of the cerebellum. In situ hybridization experiments revealed NGFR mRNA within Purkinje cells in a pattern similar to that seen with immunohistochemistry. The distribution of NGFR immunoreactivity within the cerebellum exhibits a general topographic organization with the heaviest and most consistent staining occurring within the archi- and neocerebellum and weaker staining within the paleocerebellum. In fetal Cebus monkey cerebellum obtained at gestational day 50 and 70, NGFR immunoreactivity was observed as a band composed of developing Purkinje cell neurites. These profiles were seen in the paleo- and neocerebellum, but not the archicerebellum. The present investigation is the first demonstration of NGFR immunoreactive profiles in the adult monkey and human cerebellum. These findings suggest that nerve growth factor may influence locomotor and vestibular behaviors that are mediated by cerebellar circuity. The precise mode of action for the NGF/NGFR system within the cerebellum remains to be determined.

Aged↗
PubMed1985

Effects of glycoprotein synthesis inhibitor on myelination in rat cerebellum.

Effects of a glycoprotein synthesis inhibitor on myelination were investigated in rat cerebellum. The glycoprotein synthesis inhibitor, tunicamycin (TM), was injected intracranially into newborn rats. The activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the cerebellum was significantly reduced in 2-week-old animals and was restored to the normal level by age 3 weeks. When TM was injected into newborn rats every 3-4 days for a total of 6 times, CNPase activity was still low at 3 and 4 weeks. Immunohistochemical stainings for CNPase and myelin-associated glycoprotein (MAG) were performed on paraffin sections of multiple-TM-injected cerebellum at 3 weeks. The intensity of the staining with MAG antiserum in the white matter was clearly decreased in TM-treated cerebellum compared with the control. The myelin in the granule cell layer was poorly stained with CNPase antiserum in TM-treated cerebellum. Subcellular fractionation was carried out and the CNPase activity in each fraction was measured. The CNPase activity in the myelin fraction (P2A) from the TM-treated cerebellum was significantly lower than that in the control. In contrast, the activity in the synaptosomal (P2B) and microsomal (P3) fractions from the multiple-TM-injected cerebellum was higher than in those from the controls. Polyacrylamide gel electrophoretic patterns of the P2A fractions were analyzed. The P2A fraction from TM-treated cerebellum contained less Wolfgram protein than the control. These results suggest that glycoprotein synthesis plays certain roles in myelination in the central nervous system.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1990

Expression of smg p25A, a ras p21-like small GTP-binding protein, during postnatal development of rat cerebellum.

Changes in expression and localization of smg p25A, a ras p21-like small GTP-binding protein, in developing rat brain were analyzed in comparison with those of synaptophysin, a well-known synaptic vesicle-specific protein. The smg 25A mRNA was detected in whole brain of rat fetus at 14 days of gestation and its level was increased along with the age and reached the maximum level at postnatal day (P) 20. In postnatal cerebellum, the smg25A mRNA level was also increased age-dependently and the maximum level was observed at P30. Immunoblot analysis with an anti-smg p25A monoclonal antibody (MAb SG-11-7) and an anti-synaptophysin monoclonal antibody (SY 38) showed that expression of both smg p25A and synaptophysin was increased age-dependently in postnatal rat cerebellum. By immunofluorescent cytochemical study with the anti-smg p25A antibody, bright fluorescence was observed in the molecular layer of cerebellum and it was increased in accordance with the cerebellar development. In early postnatal cerebellum, the perikarya of Purkinje cells and the white matter were brightly stained with the antibody, but the fluorescence of these portions was faint in adult cerebellum. The anti-synaptophysin monoclonal antibody also stained the molecular layer of cerebellum but the perikarya of Purkinje cells and the white matter had only a weak immunoreactivity with the antibody irrespective of the age. These results indicate that smg p25A is predominantly present in the nerve terminals and that its amount is increased along with the development of postnatal rat cerebellum. Our results also suggest that smg p25A and synaptophysin have the different kinetics of synthesis, transport, and/or turnover in developing rat cerebellum.

Aging↗
PubMed1982

Experimental and immunohistochemical studies on the cerebellar substance P of the rat: localization, postnatal ontogeny and ways of entry to the cerebellum.

With the indirect immunofluorescence technique, the localization (including the postnatal ontogeny) of substance P in the cerebellum, and the ways of entry of substance P-containing fibers into the cerebellum were explored. In the newborn rat cerebellum, dense fiber bands of axons with substance P-like immunoreactivity which can be traced to the lower brain stem are found. These fibers are also traceable to the developing granular cell layer. Two weeks after birth, however, substance P-containing structures seen in the cerebellum begin to decrease progressively and in the cerebellum of the adult rats, only a small amount of substance P-containing structures is observed. The present study established that substance P-containing fibers are mostly derived from extracerebellar substance P-containing cells and demonstrated the presence of three sites of entry of these substance P-containing fibers to the cerebellum, via (1) the inferior cerebellar peduncle, (2) the fasciculus uncinatus and (3) the middle cerebellar peduncle, respectively. Following deafferentation of the cerebellum, substance P-accumulating fibers are observed only ventral to the lesion (i.e. on the brain stem side), while in the cerebellum a remarkable decrease of substance P-containing fibers is seen and no substance P-accumulating fibers are found dorsal to the lesion (cerebellar side).

Afferent Pathways↗
PubMed1995

Functional and binding properties of sigma receptors in rat cerebellum.

Autoradiographic studies have shown that sigma receptors are enriched in the locus coeruleus, the origin of noradrenergic projections to the cerebellum, as well as in the Purkinje, molecular, and granular layers and the interpositus cerebellar nucleus of the cerebellum itself. In contrast, the cerebellum is relatively poor in phencyclidine (PCP) binding sites, which have been historically confused with sigma sites. The high ratio of sigma to PCP receptors in cerebellum is advantageous for discriminating sigma-mediated physiological effects. sigma agonists and antagonists have been shown to regulate N-methyl-D-aspartate (NMDA)-stimulated norepinephrine release in hippocampus, which is innervated by locus coeruleus projections. We now report that sigma drugs also regulate norepinephrine release from cerebellum. In contrast to findings in the hippocampus, where regulation is via sigma 1 and sigma 2 receptors, sigma-mediated regulation in cerebellum seems to be primarily via sigma 1 receptors. In radioligand binding studies, we find that sigma receptors primarily of the sigma 1 type are present in the cerebellum. We further report that binding to sigma receptors in cerebellum is not affected by the addition of NMDA or glycine or by the presence of NMDA antagonists, suggesting that sigma receptors are not located within the NMDA-operated cation channel in this brain region.

Animals↗
PubMed2004

Effects of combined prenatal stress and toluene exposure on apoptotic neurodegeneration in cerebellum and hippocampus of rats.

Pregnant Wistar rats were exposed to 1500 ppm toluene 6 hr/day from gestational day 7-20 or to chronical mild stress from gestational day 9-20 as single exposure or in combination. Behavioural, immunohistopathological, molecular biological, and neurochemical methods were applied to investigate the offspring for developmental neurotoxicity and level of apoptosis in the brain. The number of apoptotic cells in cerebellum postnatal day 22, 24, and 27 and in hippocampus (postnatal day 22, 24, and 27) were counted after visualization by the TUNEL staining or measured by DNA-laddering technique. Caspase-3 activity was determined in cerebellum (postnatal day 6, 22, 24, and 27) and in hippocampus (postnatal day 6 and 22). TUNEL staining and DNA-laddering technique showed a marked decrease in number of apoptotic cells from postnatal day 22 to 27 in both cerebellum and hippocampus. Apparently, a peak in the number of TUNEL positive cells was identified in cerebellum at postnatal day 22. There was no statistically significant influence of exposure except that DNA-laddering in cerebellum at postnatal day 27 was increased by toluene exposure. Caspase-3 activity decreased in cerebellum and hippocampus with age. At postnatal day 6 stress and toluene, when singly exposed, increased activity in cerebellum whereas co-exposure to stress and toluene did not. Stress increased caspase-3 activity in hippocampus postnatal day 22. There was overall consistency between the results obtained by the three supplementary methods regarding the influence of exposure and age on apoptotic activity in cerebellum and hippocampus. New methods to quantitate the relative level of apoptosis measured as DNA-laddering and the caspase-3 activity in tissue are presented.

Animals↗
PubMed1998

Apoptosis in the developing cerebellum of the thyroid hormone deficient rat.

The mechanism underlying transient reduction of cell number in the developing cerebellum have been studied for several decades. In this study we analyzed cell death by apoptosis in the developing cerebellum of euthyroid and hypothyroid rats. Results showed that in both groups the apoptotic activity is limited to the internal granular layer from postnatal (p) day 2 to day 12 in euthyroid animals, with the peak at 8 days. No apoptotic cells were detected in the cerebellum of 22 days old euthyroid rats. The level of apoptosis in the cerebellum of hypothyroid rats also reached a peak at 8 days but was four times higher than in control animals. Apoptosis in hypothyroid animals was also observed at p22 and corresponds to the value found in the time of the apoptotic peak in euthyroid cerebellum. At the age of 42 days, no apoptotic cells were found in the cerebellum of either group. Furthermore, it appears that the hormone also plays a role in the disappearance of the external germinal layer, since its presence is still apparent in 42 day old hypothyroid cerebellum. Hence, our results suggest that the deficiency of thyroid hormone (TH) not only increases, but also extends apoptosis during rat cerebellum development and affects the disappearance of the external germinal layer.

Aging↗