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PubMed1992

Localization of AMPA receptors in the hippocampus and cerebellum of the rat using an anti-receptor monoclonal antibody.

The primary amino acid sequences of the kainate binding proteins from the amphibian and avian central nervous systems are homologous with the functional alpha-amino-3-hydroxyl-5-methyl-isoxazole-4-propionate receptors that have been cloned from rat brain. In this study, we have analysed the anatomical and subcellular distribution of the alpha-amino-3-hydroxyl-5-methyl-isoxazole-4-propionate receptors in the rat hippocampus and cerebellum, using a monoclonal antibody that was raised against a kainate binding protein purified from frog brain. Immunoblots of rat hippocampus and cerebellum, and membranes from COS cells transfected with rat brain alpha-amino-3-hydroxyl-5-methyl-isoxazole-4-propionate receptor cDNAs (GluR1, GluR2, or GluR3) showed a major immunoreactive band migrating at a relative molecular weight of 107,000. In the cerebellum, an additional immunoreactive protein of approximately 128,000 mol. wt was also seen on immunoblots probed with the antibody. The distribution of this protein is apparently restricted to the cerebellum since the 128,000 mol. wt band was not present in other brain areas examined. The identity of the 128,000 mol. wt cerebellar protein is not known. Immunocytochemical analyses of the hippocampus demonstrated that alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate receptor subunits are present in the cell bodies and dendrites of pyramidal cells. The granule cells were also immunostained. All of the pyramidal cell subfields were heavily labeled. In the pyramidal cell bodies, a high level of immunoreactivity was observed throughout the cytoplasm. In the cerebellum, the Purkinje cell bodies and dendrites also displayed very high levels of immunoreactivity. In addition to the Purkinje neurons, the Bergmann glia and some Golgi neurons were clearly immunostained. Subcellular fractionation and lesioning experiments using the excitotoxin domoic acid indicated that the alpha-amino-3-hydroxyl-5-methyl-isoxazole-4-propionate receptor subunits were associated with postsynaptic membranes. Direct visualization of the immunoreactivity using electron microscopy confirmed the postsynaptic localization of the staining in the dendritic areas in both the hippocampus and the cerebellum. Thus, unlike the kainate binding proteins, which are found primarily extrasynaptically in the frog and on glial cells in the chicken cerebellum, the GluR1, GluR2, and GluR3 receptor subunits are localized to the postsynaptic membrane in the dendrites of neurons in the rat central nervous system.

Amygdala↗
PubMed2006

Involvement of the human cerebellum in short-term and long-term habituation of the acoustic startle response: a serial PET study.

OBJECTIVE: Numerous studies have shown an involvement of the human cerebellum in motor learning, but little is known about the role of the cerebellum in learning of unspecific aversive reactions. The present study sought to distinguish which areas of the human cerebellum and brain-stem are involved in short-term habituation (STH) and long-term habituation (LTH) of the acoustic startle response. METHODS: On 5 consecutive days 42 acoustic startle stimuli were applied each day in 8 male healthy subjects. On the first and on the fifth day of the experiment [15O]H2O PET scans were performed. RESULTS: Electromyographic recordings revealed a significant decrease of the startle response within each day (STH) and across the 5 days of the experiment (LTH). On both days a decrease of regional cerebral blood flow (rCBF) across PET scans was found in the medial cerebellum most probably reflecting reduced sensory feedback during STH. Between days an increase of rCBF in the dorsomedial pons, in the mesencephalon and in an area of the medial cerebellum was observed. These activations may reflect increased inhibition of the startle response during LTH and correspond to previous animal lesion studies. Furthermore, during LTH an increase of rCBF within the lateral cerebellum in lobule HVI/Crus I was detected. CONCLUSIONS: These results suggest that distinct parts of the medial and lateral cerebellum are involved in habituation of the acoustic startle response. Lobule HVI/Crus I most likely plays a more general role in implicit learning processes considering its involvement in several conditioning paradigms. SIGNIFICANCE: The results of the present study contribute to the understanding of cerebellar involvement in learning of unspecific aversive reactions.

Acoustic Stimulation↗
PubMed1997

Quantitative autoradiographic studies of dopamine D3 receptors in rat cerebellum using [125I]S(-)5-OH-PIPAT.

Recently, [125I]S(-)5-OH-PIPAT (5-hydroxy-2-(N-n-propyl-N-3'-iodo-2'-propenyl)amino-tetralin) was reported to be a selective radioiodinated ligand for dopamine D2-like receptors. This ligand displayed a high binding affinity (Kd = 0.3-0.4 nM) and an agonist binding profile to dopamine D2 and D3 receptors expressed in HEK293 cells and dopamine D4 receptors expressed in CHO cells. Herein, a series of studies to characterize D3 receptors in native tissues is presented. Based on studies of the distribution of receptor mRNA, D3, but not D2, receptors are present in the rat cerebellum. Quantitative autoradiographic experiments using [125I]S(-)5-OH-PIPAT to label molecular layers 9 and 10 of rat cerebellum were conducted. Saturation experiments demonstrated that [125I]S(-)5-OH-PIPAT bound with high affinity (Kd = 0.1 nM) to a low density (approximately 3 fmol/mg protein) of sites in molecular layers 9 and 10 of rat cerebellum. Increasing concentrations of Gpp(NH)p, but not ATP, decreased the specific binding of [125I]S(-)5-OH-PIPAT in rat cerebellum slices. In comparison studies, binding of [125I]NCQ298, a dopamine D2/D3 receptor antagonist, with a similar affinity (Kd = 0.2 nM) for D3 receptors as [125]S(-)5-OH-PIPAT, was not sensitive to Gpp(NH)p. Analysis of inhibition by S(-)5-OH-PIPAT of [125I]NCQ298 binding to rat cerebellum resulted in two-site binding with IC50 values of 0.07 nM and 6.0 nM. In the presence of GTP (300 microM), the data best fit a one-site model with an IC50 value of 1.6 nM. Agonists and antagonists inhibited the binding of [125I]S(-)5-OH-PIPAT in the cerebellum with a rank order of potency consistent with an interaction at D3 receptors. These results indicate that [125I]S(-)5-OH-PIPAT binds to D3 receptors in rat cerebellum. Furthermore, [125I]S(-)5-OH-PIPAT binds to GTP sensitive and GTP insensitive states of D3 receptors with distinctive high and low affinity states, respectively.

Animals↗
PubMed2003

Differential modulation of apoptosis-associated proteins by ethanol in rat cerebral cortex and cerebellum.

Chronic ethanol treatment caused a differential modulation of apoptosis-associated proteins, cytochrome c release, concomitant with procaspase-9 and procaspase-3 activation leading to oligonucleosomal DNA fragmentation in rat cerebral cortex and cerebellum. Caspase-3 proform (32 kDa) showed decreased immunoreactivity in cortex and cerebellum, while the cleaved active fragment (17 kDa) increased significantly in cerebellum after ethanol treatment. Further, chronic ethanol treatment increased caspase-3 activity in cortex and to a higher extent in cerebellum, which was further confirmed by blocking experiments with caspase-3 specific inhibitor, N-acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO). We tested whether activated caspase-3 cleaves downstream substrates such as poly (ADP-ribose) polymerase-1 and protein kinase C-delta (PKC-delta). Western blots showed poly (ADP-ribose) polymerase-1 cleavage to its signature fragment of 85 kDa and decreased levels of PKC-delta in cerebral cortex and cerebellum after ethanol treatment, suggestive of caspase-3 activation. Elevated caspase-3 activity in cerebellum than cortex correlating with cytochrome c, caspase-9, active caspase-3 (p17), poly (ADP-ribose) polymerase-1 and PKC-delta data, suggests a mechanism by which ethanol might be exerting pro-apoptotic events in brain and how selective brain regions such as cerebellum are vulnerable to ethanol neurotoxicity in terms of cell death.

Animals↗
PubMed2001

Increased variability of paced finger tapping accuracy following repetitive magnetic stimulation of the cerebellum in humans.

Imaging and lesion studies suggest that the cerebellum is involved in the self-generation of timed motor responses. Using repetitive transcranial magnetic stimulation (rTMS), we studied the effects of transient disruption of the lateral or medial cerebellum on a paced-finger-tapping task (PFT). Results show greater variability on the PFT task following a 5 min train of 1 Hz rTMS to the medial cerebellum. Magnetic stimulation of the lateral cerebellum or motor cortex, and sham stimulation, had no effect on performance. Expanding the results of neuroimaging studies, these data show the causal link between activity in the medial cerebellum and the production of timed movements. This is the first demonstration of the feasibility of transiently disrupting the cerebellum by rTMS and inducing behavioral effects. This method of 'virtual lesions' can expand the study of the role of the cerebellum in motor control and cognition.

Adult↗
PubMed2001

Hyperthermia induces gene expression of heat shock protein 70 and phosphorylation of mitogen activated protein kinases in the rat cerebellum.

In-vivo heat-shock induced heat shock factor (HSF) DNA-binding activity and accumulation of heat shock protein (hsp)70 mRNA in newborn and adult rat cerebellum was studied. We identified a high basal level of c-Jun N-terminal kinase (JNK) and p38 MAP kinase phosphorylation in the cerebellum, independently of age. Hyperthermia increased JNK1, decreased JNK2 but did not modify JNK3 phosphorylation in the newborn cerebellum, whereas decreased the phosphorylation of both JNK1 and JNK3 in adult rats. During recovery from hyperthermia, JNK2 phosphorylation returned to control level in the newborn, JNK1 appeared hyperphosphorylated only in the newborn, and JNK3 in all animals. JNK2 never appeared phosphorylated in the adult cerebellum. Hyperthermia increased p38 MAP kinase phosphorylation in the cerebellum, with different trends in newborn and adult rats during recovery. Heat shock increased extracellular signal-regulated kinase phosphorylation concomitant to tyrosine kinase receptor activation (epidermal growth factor-receptor in the newborn and insulin-like growth factor-receptor in the adult cerebellum). The behavior of stress kinases may underlie a different age-related vulnerability to heat stress of the cerebellum.

Aging↗
PubMed1995

Identification and characterization of the type-IVA cyclic AMP-specific phosphodiesterase RD1 as a membrane-bound protein expressed in cerebellum.

An antiserum was generated against a dodecapeptide whose sequence is found at the C-terminus of a cyclic AMP (cAMP)-specific, type-IVA phosphodiesterase encoded by the rat 'dunc-like' cyclic AMP phosphodiesterase (RD1) cDNA. This antiserum identified a single approximately 73 kDa protein species upon immunoblotting of cerebellum homogenates. This species co-migrated upon SDS/PAGE with a single immunoreactive species observed in COS cells transfected with the cDNA for RD1. Native RD1 in cerebellum was found to be predominantly (approximately 93%) membrane-associated and could be found in isolated synaptosome populations, in particular those enriched in post-synaptic densities. Fractionation of lysed synaptosomes on sucrose density gradients identified RD1 as co-migrating with the plasma membrane marker 5'-nucleotidase. Laser scanning confocal and digital deconvolution immunofluorescence studies done on intact COS cells transfected with RD1 cDNA showed RD1 to be predominantly localized to plasma membranes but also associated with the Golgi apparatus and intracellular vesicles. RD1-specific antisera immunoprecipitated phosphodiesterase activity from solubilized cerebellum membranes. This activity had the characteristics expected of the type-IV cAMP phosphodiesterase RD1 in that it was cAMP specific, exhibited a low Km cAMP of 2.3 microM, high sensitivity to inhibition by 4-[3-(cyclopentoxyl)-4-methoxyphenyl]-2-pyrrolidone (rolipram) (Ki approximately 0.7 microM) and was unaffected by Ca2+/calmodulin and low concentrations of cyclic GMP. The phosphodiesterase activities of RD1 solubilized from both cerebellum and transfected COS cell membranes showed identical first-order thermal denaturation kinetics at 50 degrees C. Native RD1 from cerebellum was shown to be an integral protein in that it was solubilized using the non-ionic detergent Triton X-100 but not by either re-homogenization or high NaCl concentrations. The observation that hydroxylamine was unable to cause the release of RD1 from either cerebellum or COS membranes and that [3H]palmitate was not incorporated into the RD1 protein immunoprecipitated from COS cells transfected with RD1 cDNA, indicated that RD1 was not anchored by N-terminal acylation. The engineered deletion of the 25 residues forming the unique N-terminal domain of RD1 caused both a profound increase in its activity (approximately 2-fold increase in Vmax) and a profound change in intracellular distribution. Thus, immunofluorescence studies identified the N-terminal truncated species as occurring exclusively ion the cytosol of transfected COS cells. The cDNA for RD1 thus appears to encode a native full-length type-IVA phosphodiesterase that is expressed in cerebellum.(ABSTRACT TRUNCATED AT 400 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2005

Reciprocal evolution of the cerebellum and neocortex in fossil humans.

Human brain evolution involved both neurological reorganization and an increase in overall brain volume relative to body mass. It is generally difficult to draw functional inferences about the timing and nature of brain reorganization, given that superficial brain morphology recorded on fossil endocasts is functionally ambiguous. However, the cerebellum, housed in the clearly delineated posterior cranial fossa, is functionally and ontologically discrete. The cerebellum is reciprocally connected to each of 14 neocortical regions important to human cognitive evolution. Cerebellar volume varies significantly relative to overall brain volume among mammalian orders, as well as within the primate order. There is also significant diachronic variation among fossil human taxa. In the australopithecines and early members of the genus Homo, the cerebral hemispheres were large in proportion to the cerebellum, compared with other hominoids. This trend continued in Middle and Late Pleistocene humans, including Neandertals and Cro-Magnon 1, who have the largest cerebral hemispheres relative to cerebellum volume of any primates, including earlier and Holocene humans. In recent humans, however, the pattern is reversed; the cerebellum is larger with respect to the rest of the brain (and, conversely, the cerebral hemispheres are smaller with respect to the cerebellum) than in Late Pleistocene humans. The cerebellum and cerebral hemispheres appear to have evolved reciprocally. Cerebellar development in Holocene humans may have provided greater computational efficiency for coping with an increasingly complex cultural and conceptual environment.

Biological Evolution↗
PubMed2003

Expression and distribution of voltage-gated sodium channels in the cerebellum.

In order to understand the effects of sodium channels on synaptic signaling and response in the cerebellum, it is essential to know for each class of neuron what sodium channel isoforms are present, and the properties and distribution of each. Sodium channels are heteromultimeric membrane proteins, consisting of a large alpha subunit that forms the pore, and one or more beta subunits. Ten genes encode an alpha subunit in mammals, and of these, four are expressed in the cerebellum: Nav1.1, Nav1.2, Nav1.3 and Nav1.6. Three genes encode beta subunits (Nabeta1-3), and all three are expressed in the cerebellum. However, Nav1.3 and Nabeta3 have been found only in the developing cerebellum. All sodium channels recorded in the cerebellum are TTX-sensitive with similar kinetics, making it difficult to identify the isoforms electrically. Thus, most of the expression studies have relied on techniques that allow visualization of sodium channel subtypes at the level of mRNA and protein. In situ hybridization and immunolocalization studies demonstrated that granule cells predominantly express Nav1.2, Nav1.6, Nabeta1, and Nabeta2. Protein for Nav1.2 and Nav1.6 is localized primarily in granule cell parallel fibers. Purkinje cells express Nav1.1, Nav1.6, Nabeta1 and Nabeta2. The somato-dendritic localization of Nav1.1 and Nav1.6 in Purkinje cells suggests that these isoforms are involved in the integration of synaptic input. Deep cerebellar nuclei neurons expressed Nav1.1 and Nav1.6 as well as Nabeta1. Bergmann glia expressed Nav1.6, but not granule cell layer astrocytes. Some sodium channel isoforms that are not expressed normally in the adult cerebellum are expressed in animals with mutations or disease. Electrophysiological studies suggest that Nav1.6 is responsible for spontaneous firing and bursting features in Purkinje cells, but the specialized functions of the other subunits in the cerebellum remain unknown.

Animals↗
PubMed2004

The vestibulo-ocular reflex as a model system for motor learning: what is the role of the cerebellum?

Motor systems are under a continuous adaptive process to maintain behavior throughout developmental changes and disease, a process called motor learning. Simple behaviors with easily measurable inputs and outputs are best suited to understand the neuronal signals that contribute to the required motor learning. Considering simple behaviors, the vestibulo-ocular reflex (VOR) allows quantification of its input and motor output and its neural circuitry is among the best documented. The main candidates for plastic change are the cerebellum and its target neurons in the brainstem. This review focuses on recent data regarding the involvement of the cerebellum in VOR motor learning. Learning can be divided into that acutely acquired over a period of hours and that chronically acquired over longer periods. Both acute and chronic learning have three phases named acquisition, consolidation, and retention. The cerebellar role in retention is disputed, but there is a consensus on the need of an intact cerebellum for acquisition. Data from neuronal recording, lesion studies and transgenic mouse experiments is complex but suggests that the signal representation in the cerebellum contains aspects of both motor output and sensory input. The cerebellum apparently uses different mechanisms for acute and chronic learning as well as for increases and decreases in VOR gain. Recent studies also suggest that the signal content in the cerebellum changes following learning and that the mechanisms used for chronic adaptation involve not only changes in a head velocity component but also in the efference copy of an eye movement command signal reaching Purkinje cells. This data leads to a new conceptual framework having implications for developing theories on the role of the cerebellum in motor learning and in the search for plastic elements within the VOR circuitry. For chronic learning we hypothesize that changes in the head velocity information traveling through the circuitry occur in parallel with changes in the integrator pathway and the efference copy pathway. We further propose that these changes are necessary to maintain the broadband characteristics of the learned behavior.

Animals↗
PubMed1987

Immunocytochemical characterization of glutamate dehydrogenase in the cerebellum of the rat.

The immunocytochemical distribution of glutamate dehydrogenase was studied in the cerebellum of the rat using antibodies made in rabbit and guinea pig against antigen purified from bovine liver. Antiserum was found to block partially enzymatic activity both of the purified enzyme and of extracts of the rat cerebellum. Using immunoblots of proteins of rat cerebellum, a major immunoreactive protein and several minor immunoreactive proteins were detected with antiserum. Only a single immunoreactive protein was detected using affinity-purified antibody preparations. This protein migrates with a molecular weight identical to that of the subunit of glutamate dehydrogenase. Further evidence that the antibodies were selective for glutamate dehydrogenase in rat cerebellum was obtained through peptide mapping. Purified glutamate dehydrogenase and the immunoreactive protein from rat cerebellum generated similar patterns of immunoreactive peptides. No significant cross-reaction was observed with glutamine synthetase. Immunocytochemistry was done on cryostat- and Vibratome-cut sections of the cerebellum of rats that had been perfused with cold 4% paraformaldehyde. Glial cells were found to be the most immunoreactive structures throughout the cerebellum. Most apparent was the intense labeling of Bergmann glial cell bodies and fibers. In the granule cell layer, heavy labeling of astrocytes was seen. Purkinje and granule cell bodies were only lightly immunoreactive, whereas stellate, basket, and Golgi cells were unlabeled. Labeling of presynaptic terminals was not apparent. These findings suggest that glutamate dehydrogenase, like glutamine synthetase, is enriched in glia relative to neurons.

Animals↗
PubMed2002

Historical review of the significance of the cerebellum and the role of Purkinje cells in motor learning.

Classic studies of the cerebellum before the middle of the twentieth century established the structural entity of the cerebellum and characterized its function as enabling animals and humans to carry out smooth and accurate movements, even at a high speed and without visual feedback. In the 1960s, neuronal circuit structures of the cerebellum were analyzed in detail, which promoted computational approaches toward the study of neuronal network principles of the cerebellum. In the 1970s and 1980s, vestibulo-ocular reflex adaptation, adaptive locomotion, eye blink conditioning, and learning in hand/arm movement were established as effective experimental paradigms for investigating neural mechanisms of cerebellar functions. In the 1980s, long-term depression (LTD) was discovered and considered as a memory process in the cerebellum; in the 1990s, complex signal transduction processes underlying LTD were revealed. It was also in the 1980s that computational approaches were advanced for modeling control system functions of the cerebellum. Currently, there are two alternative models proposed for VOR adaptation. In this decade, we envisage new developments toward the fusion of knowledge of the cerebellum at molecular and cellular levels and those in systems and computation. Studies of LTD will play a key role in pursuing this direction.

Animals↗
PubMed1999

Thyroid hormone regulates the expression of laminin in the developing rat cerebellum.

In the rat cerebellum, migration of neurons from the external granular layer to the internal granular layer occurs postnatally and is dependent upon the presence of thyroid hormone. In hypothyroidism, many neurons fail to complete their migration and die. Key guidance signals to these migrating neurons are provided by laminin, an extracellular matrix protein that is fixed to the surface of astrocytes. Expression of laminin in the brain is developmentally timed to coincide with neuronal growth spurts. In this study, we examined the role of thyroid hormone on the expression and distribution of laminin in the rat cerebellum. We show that laminin content steadily increased 2- to 3-fold from birth to maximal levels on postnatal day 8-10 then steadily decreased to a plateau by postnatal day 12 in the euthyroid cerebellum. Immunoreactive laminin appeared in the molecular layer of the euthyroid cerebellum by postnatal day 4, reached maximal intensity by postnatal day 8-10, and was gone by postnatal day 14. In contrast, laminin content in the hypothyroid cerebellum remained unchanged from birth until postnatal day 10 and then increased to maximal levels over the next two days; maximal levels were approximately 35% less than those levels in the euthyroid cerebellum. Laminin staining did not appear in the molecular layer of the hypothyroid rat cerebellum until postnatal day 10, reached maximal intensity by postnatal day 15 and disappeared by postnatal day 18, despite the continued presence granular neurons in the external granular layer. These data indicate that the disruption of the timing of the appearance and regional distribution of laminin in the absence of thyroid hormone may play a major role in the profound derangement of neuronal migration observed in the cretinous brain.

Aging↗
PubMed1996

Speech, language, and the cerebellum.

The cerebellum can affect speech and language in a number of ways. The most obvious is dysarthria when motor movements are deprived of the regulatory control, which is one of the main functions of the cerebellum. Less well-known is cerebellar mutism, which most often occurs after the removal of a cerebellar tumour. It is unlikely that this is simply the result of dysarthria. The most controversial aspect of cerebellar function, and the main stress of this paper, is the contribution it may make to language production. A number of studies have suggested that the cerebellum can, indeed, be involved in both cognition and language. A number of these are reviewed, in particular, the results of diffuse and focal lesions of the cerebellum, and how these can affect the function of the cerebrum; and conversely how cerebral lesions can cause changes in the cerebellum. Positron emission tomography (PET) has been essential in the assessment of these patients. During human evolution parts of the cerebellum and their connections have enlarged enormously, and it would be surprising if these parts of the brain had not taken on new roles. To regard the cerebellum as only serving motor function is too narrow a concept.

Brain Diseases↗
PubMed1993

Differential sequestration of parasitized erythrocytes in the cerebrum and cerebellum in human cerebral malaria.

Sequestration of parasitized red blood cells (PRBC) in the microvessels results in impairment of microcirculation with organ dysfunction in complicated human Plasmodium falciparum malaria. In cerebral malaria patients, the percentage of small blood vessels with PRBC sequestration is higher in the brain than in other organs. The clinical severity of cerebral malaria depends on the level of PRBC sequestration in the brain. In our study, postmortem samples from cerebrum and cerebellum of 16 patients who died of P. falciparum malaria were examined and compared using light microscopy. In the cerebellum, the percentage of microvessels with PRBC sequestration was higher than that in the cerebrum. The difference in sequestration rates between cerebrum and cerebellum is statistically significant (P < 0.05). There is a higher degree of vascularity in the cerebellum (7 vessels/mm2) than in the cerebrum (5 vessels/mm2), and the difference is also statistically significant (P < 0.025). Perivascular hemorrhages also occur more frequently in the cerebellum than in the cerebrum. The results of this study, which show that differential sequestration of PRBC occurs in the microvessels of the cerebrum and cerebellum, explain the varied neurologic manifestations that result from cerebral and cerebellar dysfunction in human cerebral malaria. This study also reveals the necessity of postmortem histologic examination of the cerebellum in every suspected case of cerebral malaria.

Brain↗
PubMed1976

[The so-called pressure zone of the cerebellum].

Systematic studies on the so-called cone of basal parts of the cerebellum employing a scale of either qualitative and quantitative intensity revealed the following: A cone extension of basal cerebellum parts is to be observed in 80.9% of random post-morten examination cases with insignificant differences in sex. Cerebellum cone frequency amounts to 12.8% in babies, up to 66.7% in infants from 1 to 14 years of age, and to 91.8% in persons above 15 years of age. Cones are not found in foetusses. Cones are almost exclusively formed with the participation of those cerebellum parts adjacent to the tonsils, so that the termin "tonsil cone" is incorrect. Cerebellum cones can be distinguished by various degrees in size. The 1st degree corresponds to a cone height of 5 mm, 2nd degree between 5 and 10 mm, and 3rd degree to 10 mm and above. Statistical analysis shows that the cone height follows normal distribution, the mean value of height being 4.8 mm. No correlation has been found between the cone height and clinically detected state of cerebral pressure as well as between space requiring processes during the post-mortem examination. Hence the term "pressure cone" is wrong. There is a positive correlation between cone formation and other so-called morphological symptoms of cerebral pressure. But it is doubtful, whether these symptoms may be regarded as a result of pressure on the brain. The occurrence of a cerebellum basal sphere cone is considered a normal filling up process of any internal space in the skull during brain acceleration. It is only in exceptional cases of cone sizes 10 mm and more, that cone formation is significant for the diagnosis of a possible increase in cerebral volume. Considering the obviously minimal significance of basal cerebellum cone in diagnosing an increase in cerebral volume, the following is a suggestion to prove a condition of cerebral pressure by means of complementary space determination of the skull.

Adolescent↗
PubMedDate not supplied

[Current concepts regarding the cerebellum and cognition].

OBJECTIVE: To review the main cognitive processes regulated by the cerebellum and the anatomical circuits involved in their clinical correlation. DEVELOPMENT: The cerebellum is generally regarded as a regulator of motor function with a key role in movement coordination. Clinical evidence of the relation of the cerebellum to neural functions typically considered as cortical, is supplied by several neuropsychological alterations detected in both degenerative disorders and acute insult to the region such as vascular event and surgery. More anatomical circuits between the cerebellum and several cortical areas and limbic system, with the ventral pons region as main afference and efference relay of all these pathways. Cerebellar structures that are phylogenetically older such as the floculonodullar lobe, vermix, fastigial nuclei and globus nuclei have a tight relationship to emotional control and autonomic manifestations. More complex circuits are founded in the regulation of learning, motor planning and language. Functional imaging studies have helped to confirm the relationship between the cerebellum and memory processes, finding a selective activation of lateral regions during to cerebellar damage, such a frontal like syndromes, memory deficits and aphasia and even though dysmetria with incoordination between mental process velocity and its motor execution. CONCLUSIONS: All the data from clinical and functional studies indicate that the cerebellum has a central co-ordinating function not only of movement but also regulating thought. The cerebellum should, therefore, be reconsidered as a complex neurone system at much the same level as the more advanced cortical structures.

Cerebellum↗
PubMed2000

Stereological analysis of the cerebellum of 24-day old rats with propylthiouracil-induced hypothyroidism.

OBJECTIVE: To investigate the structural parameters of the developing cerebellum in propylthiouracil (PTU)-induced hypothyroidism during pre and postnatal stages in 24 day old rat pups. METHOD: Hypothyroidism was induced by feeding the breeding dams with PTU in water before and during copulation, pregnancy and lactation and the pups through the dams and ingestion in water. The number of control and treated dams and pups was five for each dam group and twelve and thirteen for pups respectively. The whole cerebellum was dissected out from the pups and processed routinely for histological examination and morphometric analysis. The total volumes of cerebellum, intracerebellar nuclei and cerebellar compartments were estimated by Cavalieri method. The mean numerical densities of neurones and neuroglia in the intracerebellar nuclei and Purkinje, granule and combined stellate and basket cells in cerebellar cortex were estimated using optical disector and the total numbers calculated as the product of the respective numerical densities and reference volumes. RESULTS: The treated dams and pups had relatively lower mean body weights and etraiodothyronine (T4) serum concentrations. The serum Triiodothyronine (T3) was normal and lower in the treated dams and pups respectively. The differences in the respective body weights and dam T4 concentration in treated dams and pups were significant (p<0.05) compared to the control. Morphometric results showed that the mean volumes of cerebellum, intracerebellar nuclei, white matter, internal granular layer, molecular layer and the cerebellar cortex were lower and the differences between the values for each parameter were significant (p<0.05) in the treated pups compared to the control. The mean numerical densities of neurones and neuroglia in the intracerebellar nuclei (Nvne; Nvgl) and the combined stellate and basket cells (Nvsb) in the cerebellar cortex were relatively higher and the mean values for the respective numerical densities of Purkinje and granule cells (Nvpu; Nvgr) were relatively lower in the treated pups compared to the control. On the other hand the treated pups had relatively lower values for the respective total numbers of neurons (Nne), neuroglia (Ngl), Purkinje (Npu), granule (Ngr) and the combined stellate and basket (Nsb) cells compared to the control. The differences between the respective values for Nvne, Nvsb, Npu, and Ngr, were significant (p<0.05). CONCLUSION: These results show that rat pups with PTU-induced hypothyroidism have relatively lower mean values for the structural parameters in the cerebellum when compared to control pups. This confirms that growth and maturation of the cerebellum is dependent on the maintenance of normal T4 and T3 levels, underscores the magnitude of the deviations from the normal and sheds light on possible structural limitations in the cerebellum in cretins.

Animals↗