The purpose of this study is to identify the differences of zebrin II expression between ataxic pogo and normal Balb/C mouse cerebellum. Zebrin II is expressed by subsets of Purkinje cells that form an array of parasagittal bands that extend rostrocaudally throughout the cerebellar cortex, separated by similar bands of Purkinje cells that do not express zebrin II. Zebrin II immunoreactivity was localized in the perikarya of Purkinje cells, and the dendrites. Distribution of zebrin II-immunoreactive Purkinje cells were very similar pattern in pogo and Balb/C mouse cerebellum. But, in the lobule III, distribution of zebrin II expression was different between pogo and Balb/C mouse cerebellum. In lobule III of Balb/c mouse cerebellum, 10~15 zebrin II-immunoreactive Purkinje cells were observed and clustered to form a parasagittal bands. On the other hand, zebrin II expressions of lobule III in pogo mouse cerebellum showed a little different patterns. In lobule III of pogo mouse cerebellum, three bilateral zebrin II immunoreactive parasagittal band were observed. P1 band was almost same with lobule III of Balb/C mouse cerebellum. But, P2 bands were composed of 50~60 Purkinje cells which were immunoreactive with zebrin II. These kind of thickening in zebrin II expression of pogo mouse cerebellum may be due to the genetical difference. Furthermore, these results may provide useful information with further ataxic pogo mice cerebellum studies.
Animals ; Cerebellar Cortex ; Cerebellum* ; Dendrites ; Hand ; Immunohistochemistry ; Mice* ; Purkinje Cells

Paraneoplastic cerebellar degeneration (PCD), the one of rare paraneoplastic syndromes, refer to clinical disorders associated mostly with lung, ovarian and breast cancer, but not directly caused by cancer or its metastasis. PCD is a condition whereby the Purkinje cells of the cerebellar cortex are damaged secondary to an autoimmune process. We report here on the case of PCD of subacute onset in a patient at 7 months after surgery for ovarian cancer. Although the cases of PCD has rarely been reported, the present case appears to be the first in Korea in which PCD was associated with anti-Yo antibody in patient with chemotherapy-responsive ovarian cancer. The clinical significance of PCD associated with anti-Yo antibody is reviewed.
Breast Neoplasms ; Cerebellar Cortex ; Humans ; Korea ; Lung ; Neoplasm Metastasis ; Ovarian Neoplasms ; Paraneoplastic Cerebellar Degeneration ; Paraneoplastic Syndromes ; Purkinje Cells

Cerebellum is known as a center for sensory/motor coordination and memory storage in motor learning. The vestibular nuclei have extensive afferent and efferent connections with posterior cerebellum which can be referred to as vestibulocerebellum. While secondary vestibular afferents are distributed bilaterally in the vestibulocerebellum, primary afferents may directly project to ipsilateral vestibulocerebellum. The Purkinje cells which are the only output neurons from the cerebellar cortex receive vestibular information via parallel and climbing fibers. That information is integrated and encoded in the Purkinje cells and then conveyed into the vestibular nucleus or deep cerebellar nucleus, which permits adaptive guidance of vestibular function by the vestibulocerebellum.
Cerebellar Cortex ; Cerebellar Nuclei ; Cerebellum ; Electrophysiology ; Learning ; Membranes ; Memory ; Neurons ; Patch-Clamp Techniques ; Purkinje Cells ; Vestibular Nuclei

The pogo mouse is a new ataxic mutant derived from a Korean wild mouse. The pogo mutation is inherited as an autosomal recessive trait on chromosome 8. Mutations in gene coding for the alpha(1A)subunit of voltagegated P/Q-type Ca(2+) channel have been shown to cause phenotypes in humans and mice, i.e., tottering, leaner, rolling mouse mouse Nagoya. Using immunohistochemistry, the expression of the alpha(1A)subunit of voltage-gated P/Q-type Ca(2+) channel was examined in pogo mice cerebellum including deep cerebellar nuclei (DCN). We observed alpha(1A)immunoreactivity in the cerebellar cortex (Purkinje cell and granule cell) and DCN of ataxic pogo mice and heterozygote control mice. There was no difference in cerebellar cortical alpha(1A)immunoreactivity between ataxic pogo mice and heterozygous littermate controls (pogo/+). However, we observed alpha(1A)immunoreactivity in the Purkinje cells of control and ataxic pogo mice cerebellum and DCN. We found a significant difference between pogo and heterozygous controls in terms of alpha(1A)immunoreactivities in the DCN. alpha(1A)immunoreactivity in this nucleus in pogo was much higher than in heterozygous littermate controls. No significant differences were observed in the interposed nucleus between pogo and heterozygous controls, but we found that the alpha(1A)subunits were clearer and more abundant in the lateral and medial regions of pogo than in control mice in these regions, where only weak immunoreactivity was observed. This elevated expression of the alpha(1A)subunit in deep cerebellar neurons of pogo might be a compensation for the altered function of P/Q type calcium channel and be related with the induction of the ataxic phenotype in pogo mice.
Animals ; Ataxia ; Calcium Channels* ; Calcium* ; Cerebellar Cortex ; Cerebellar Nuclei ; Cerebellum* ; Chromosomes, Human, Pair 8 ; Clinical Coding ; Compensation and Redress ; Heterozygote ; Humans ; Immunohistochemistry ; Mice* ; Neurons ; Phenotype ; Purkinje Cells

What is memory? How does the brain process the sensory information and modify an organism's behavior? Many neuroscientists have focused on the activity- and experience-dependent modifications of synaptic functions in order to solve these fundamental questions in neuroscience. Recently, the plasticity of intrinsic excitability (called intrinsic plasticity) has emerged as an important element for information processing and storage in the brain. As the cerebellar Purkinje cells are the sole output neurons in the cerebellar cortex and the information is conveyed from a neuron to its relay neurons by forms of action potential firing, the modulation of the intrinsic firing activity may play a critical role in the cerebellar learning. Many voltage-gated and/or Ca²⁺-activated ion channels are involved in shaping the spiking output as well as integrating synaptic inputs to finely tune the cerebellar output. Recent studies suggested that the modulation of the intrinsic excitability and its plasticity in the cerebellar Purkinje cells might function as an integrator for information processing and memory formation. Moreover, the intrinsic plasticity might also determine the strength of connectivity to the sub-cortical areas such as deep cerebellar nuclei and vestibular nuclei to trigger the consolidation of the cerebellar-dependent memory by transferring the information.
Action Potentials ; Automatic Data Processing ; Brain ; Cerebellar Cortex ; Cerebellar Nuclei ; Cerebellum ; Fires ; Ion Channels ; Learning* ; Memory ; Neuronal Plasticity ; Neurons ; Neurosciences ; Plastics* ; Purkinje Cells* ; Vestibular Nuclei

The toxic effects of morphine sulfate in the adult cerebral cortex and one-day neonatal cerebellum have been studied. This study was carried out to evaluate the effect of maternal morphine exposure during gestational and lactation period on the Purkinje cells and cerebellar cortical layer in 18- and 32-day-old mice offspring. Thirty female mice were randomly allocated into cases and controls. In cases, animals received morphine sulfate (10 mg/kg/body weight intraperitoneally) during the 7 days before mating, gestational day (GD 0-21) 18 or 32. The controls received an equivalent volume of saline. The cerebellum of six infants for each group was removed and each was stained with cresyl violet. Quantitative computer-assisted morphometric study was done on cerebellar cortex. The linear Purkinje cell density in both experimental groups (postnatal day [P]18, 23.40+/-0.5; P32, 23.45+/-1.4) were significantly reduced in comparison with the control groups (P18, 28.70+/-0.9; P32, 28.95+/-0.4) (P<0.05). Purkinje cell area, perimeter and diameter at apex and depth of simple lobules in the experimental groups were significantly reduced compared to the controls (P<0.05). The thickness of the Purkinje layer of the cerebellar cortex was significantly reduced in morphine treated groups (P<0.05). This study reveals that morphine administration before pregnancy, during pregnancy and during the lactation period causes Purkinje cells loss and Purkinje cell size reduction in 18- and 32-day-old infant mice.
Adult ; Animals ; Benzoxazines ; Cell Count ; Cell Size ; Cerebellar Cortex ; Cerebellum ; Cerebral Cortex ; Female ; Humans ; Infant ; Lactation ; Mice ; Morphine ; Pregnancy ; Purkinje Cells ; Viola

In the present study, we investigated the expression of apoptosis-associated proteins in the cerebellum of aged rats: IGF-I receptor (IGF-IR), nitrotyrosine (NT), p53, key pro-apoptotic gene ICH-1 (caspase-2), c-Fos and Bcl-2 family members (Bcl-2 and Bax). Twelve adult (4~6 month old) and 15 aged (24~29 month old) Sprague-Dawley rats were examined in this study. We performed immunohistochemical staining, in situ hybridization and densitometric measurement using a NIH image program (Scion Image) to determine the staining density. In adult rats, there were no immunoreactivities for insulin-like growth factor-I receptor (IGF-IR), nitrotyrosine (NT) or p53 in any region of cerebellum. However, IGF-IR immunoreactivity was found in some Purkinje cells in aged rat cerebellum. The prominent staining of NT or p53 was also localized in the Purkinje cell layer in aged rats. A high density of ICH-1 (caspase-2) immunoreactivity was observed in the molecular and Purkinje cell layers in aged rats. Immunoreactivity for c-Fos was significantly decreased in the granule cells in aged rats. Positive signal for bcl-2 was significantly decreased in the Purkinje cells and granule cells of aged rats. The most intense staining for Bax was observed in the soma of Purkinje cells of adult rats. However, Bax immunoreactivity was not changed in any layers in the cerebellar cortex of aged rats. In conclusion, this study provides the first morphological data concerning the differential regulation of apoptosisrelated genes in rat cerebellum during aging.
Adult ; Aging ; Animals ; Carisoprodol ; Cerebellar Cortex ; Cerebellum* ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Neurons* ; Purkinje Cells ; Rats* ; Rats, Sprague-Dawley ; Receptor, IGF Type 1

Sulfites are used as anti-microbial and anti-oxidant agents in the food and pharmaceutical industries. Curcumin, a flavonoid, is an Asian spice that shows neuroprotective activities. The current study aimed to stereologically assess the rats' cerebellar cortex and rotarod performance following sulfite exposure and determine the possible neuroprotective potential of curcumin. The rats were divided into five groups: distilled water, olive oil, curcumin (100 mg/kg/day), sodium metabisulfite (25 mg/kg/day), and sodium metabisulfite+curcumin. At 56 days after treatment, rotarod performance was tested, and then the cerebellum was removed for stereological analysis. The study results revealed 31%, 36%, 19% and 24% decrease in the total volume of the cerebellum, cortex, the total number of the Purkinje cells and length of the nerve fibers in the cortex per Purkinje, respectively in the sodium metabisulfite-treated rats compared to the distilled water group (p<0.01). The pre-trained animals on the rotarod apparatus were tested first on the fixed speed rotarod protocol followed by the accelerating rotarod protocol two days later. The results showed a significant decrease in the latency to fall in both test in sulfite-treated rats. The sulfite effects on the structural parameters and rotarod performance were significantly protected by the concomitant curcumin treatment (p<0.001). Sulfite can induce structural and functional changes in the rats' cerebellum and concomitant curcumin prescription plays a neuroprotective role.
Animals ; Asian Continental Ancestry Group ; Cerebellar Cortex ; Cerebellum ; Curcumin* ; Drug Industry ; Humans ; Nerve Fibers ; Olea ; Prescriptions ; Purkinje Cells ; Rats* ; Sodium* ; Spices ; Sulfites ; Water ; Olive Oil

OBJECTIVE: Propofol is an intravenously administered anesthetic that enhances γ-aminobutyric acid-mediated inhibition in the central nerve system. Other mechanisms may also be involved in general anesthesia. Propofol has been implicated in movement disorders. The cerebellum is important for motor coordination and motor learning. The aim of the present study was to investigate the propofol effect on excitatory synaptic transmissions in cerebellar cortex. METHODS: Excitatory postsynaptic currents by parallel fiber stimulation and complex spikes by climbing fiber stimulation were monitored in Purkinje cells of Wister rat cerebellar slice using whole-cell patch-clamp techniques. RESULTS: Decay time, rise time and amplitude of excitatory postsynaptic currents at parallel fiber Purkinje cell synapses and area of complex spikes at climbing fiber Purkinje cell synapses were significantly increased by propofol administration. CONCLUSION: The detected changes of glutamatergic synaptic transmission in cerebellar Purkinje cell, which determine cerebellar motor output, could explain cerebellar mechanism of motor deficits induced by propofol.
Anesthesia, General ; Anesthetics ; Animals ; Cerebellar Cortex ; Cerebellum ; Excitatory Postsynaptic Potentials ; Learning ; Movement Disorders ; Patch-Clamp Techniques ; Propofol* ; Purkinje Cells* ; Rats ; Synapses ; Synaptic Transmission

Cerebellar Purkinje cells (PCs) exhibit two types of discharge activities: simple spike (SS) and complex spike (CS). Previous studies found that noradrenaline (NA) can inhibit CS and bidirectionally regulate SS, but the enhancement of NA on SS is overwhelmed by the strong inhibition of excitatory molecular layer interneurons. However, the mechanism underlying the effect of NA on SS discharge frequency is not clear. Therefore, in the present study, we examined the mechanism underlying the increasing effect of NA on SS firing of PC in mouse cerebellar cortex in vivo and in cerebellar slice by cell-attached and whole-cell recording technique and pharmacological methods. GABA_A receptor was blocked by 100 µmol/L picrotoxin in the whole process. In vivo results showed that NA significantly reduced the number of spikelets of spontaneous CS and enhanced the discharge frequency of SS, but did not affect the discharge frequency of CS. In vitro experiments showed that NA reduced the number of CS spikelets and after hyperpolarization potential (AHP) induced by electrical stimulation, and increased the discharge frequency of SS. NA also reduced the amplitude of excitatory postsynaptic current (EPSC) of parallel fiber (PF)-PC and significantly increased the paired-pulse ratio (PPR). Application of yohimbine, an antagonist of α2-adrenergic receptor (AR), completely eliminated the enhancing effect of NA on SS. The α2-AR agonist, UK14304, also increased the frequency of SS. The β-AR blocker, propranolol, did not affect the effects of NA on PC. These results suggest that in the absence of GABA_A receptors, NA could attenuate the synaptic transmission of climbing fiber (CF)-PC via activating α2-AR, inhibit CS activity and reduce AHP, thus enhancing the SS discharge frequency of PC. This result suggests that NA neurons of locus coeruleus can finely regulate PC signal output by regulating CF-PC synaptic transmission.
Action Potentials/physiology* ; Animals ; Cerebellar Cortex/metabolism* ; Cerebellum/metabolism* ; Mice ; Norepinephrine/pharmacology* ; Purkinje Cells/metabolism* ; Receptors, Adrenergic, alpha-2/metabolism* ; Receptors, GABA-A/metabolism*