Abnormal prenatal sonographic findings in the posterior cranial fossa: a case of Joubert's syndrome.
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Joubert's syndrome is a well-documented but rare disorder characterized by a variable combination of central nervous system, respiratory, renal and eye anomalies. The most significant and constant neuropathological finding is partial or complete agenesis of the cerebellar vermis. The syndrome was first described by Joubert and colleagues as a familial agenesis of the cerebellar vermis and appears to be inherited as an autosomal recessive trait. A case of Joubert's syndrome is described in which second-trimester ultrasonography demonstrated abnormal findings in the fetal posterior fossa with associated renal abnormalities. However, postnatal sonography of the posterior fossa could not confirm the prenatal findings, and the diagnosis of Joubert's syndrome was only later established by computed tomography of the neonatal brain in the knowledge of the characteristic clinical picture. (+info)
Isolated dysarthria due to extracerebellar lacunar stroke: a central monoparesis of the tongue.
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OBJECTIVES: The pathophysiology of dysarthria can preferentially be studied in patients with the rare lacunar stroke syndrome of "isolated dysarthria". METHODS: A single study was carried out on seven consecutive patients with sudden onset of isolated dysarthria due to single ischaemic lesion. The localisation of the lesion was identified using MRI. The corticolingual, cortico-orofacial, and corticospinal tract functions were investigated using transcranial magnetic stimulation. Corticopontocerebellar tract function was assessed using 99mTc hexamethylpropylene amine oxime-single photon emission computerised tomography (HMPAO-SPECT) in six patients. Sensory functions were evaluated clinically and by somatosensory evoked potentials. RESULTS: Brain MRI showed the lesions to be located in the corona radiata (n=4) and the internal capsule (n=2). No morphological lesion was identified in one patient. Corticolingual tract function was impaired in all patients. In four patients with additional cortico-orofacial tract dysfunction, dysarthria did not differ from that in patients with isolated corticolingual tract dysfunction. Corticospinal tract functions were normal in all patients. HMPAO-SPECT showed no cerebellar diaschisis, suggesting unimpaired corticopontocerebellar tract function. Sensory functions were not affected. CONCLUSION: Interruption of the corticolingual pathways to the tongue is crucial in the pathogenesis of isolated dysarthria after extracerebellar lacunar stroke. (+info)
Cerebellar afferents from neurons in the extraocular motor nuclei: a fluorescent retrograde double-labeling study in the sheep.
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The fluorescent retrograde double labeling technique has been used to identify within the extraocular motor nuclei of the sheep the neurons projecting to the cerebellum and to provide evidence whether they are motor neurons sending collaterals to the cerebellum or a separate population of neurons. The study was performed on eight sheep. The fluorescent tracers used were Fast Blue and the diamidino yellow dihydrochloride. In one and the same animal a fluorescent tracer was injected into the extraocular muscles (EOMs) and the other into bilateral points of the vermal folia II-V and paramedian lobule, or into the vermal folia VI, VIIA and VIIB, or into the underlying fastigial nuclei. Within the oculomotor, trochlear, and abducens nuclei, almost all of the motor neurons were labeled by the tracer injected into the EOMs and only a few cells were fluorescent for the tracer infiltrated into the cerebellum. These latter labelings were present bilaterally, and their number and distribution did not show apparent differences after injecting the paramedian lobule and the vermal folia or the fastigial nucleus. Along the rostrocaudal extent of the oculomotor and trochlear nuclei, the neurons projecting to the cerebellum were intermingled with the motor neurons located in the nuclear area facing the medial longitudinal fasciculus. In the abducens nucleus they were restricted to the caudal pole of the nucleus, which is located ventrolaterally to the genu of the facial nerve. Double-labeled neurons were never found. The absence of double-labeled cells, in spite of the efficiency of the tracer infiltration into the EOMs and into the cerebellum, demonstrates that the cerebellar projections from the extraocular motor nuclei are not collaterals of the motor neurons, but axons of a separate population of neurons. (+info)
Rough surfaced smooth endoplasmic reticulum in rat and mouse cerebellar Purkinje cells visualized by quick-freezing techniques.
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The in vivo structure of the smooth endoplasmic reticulum (ER) was visualized in rat and mouse cerebellar Purkinje cells by using quick-freezing techniques followed by freeze-substitution for ultrathin-sectioning or freeze-fracturing and deep-etching for replicas. High magnification electron microscopy of the ultrathin sections revealed a surprising finding that all the smooth ER are apparently rough surfaced, and heavily studded with a large number of small dense projections. In the soma the smooth ER appears to be similar to its rough counterpart, except that the projections are slightly smaller, less electron dense and less protrusive on the ER membranes than the ribosomes. The projections were short rectangles, 20 x 20 x 6 nm3 in size, covering the cytoplasmic surface of the smooth ER in a checker-board manner where closely packed. After freeze-etching and replication, they appeared to be composed of four subparticles, surrounding a central channel. Thus the projections are very similar to the foot structure (ryanodine receptor) of the sarcoplasmic reticulum. Furthermore, they were distributed exclusively in the ER compartment and were highly concentrated especially in the smooth ER. This localization of the projections coindides with the intracellular distribution of the inositol 1,4,5-trisphosphate (IP3) receptor determined by quantitative immunogold electron microscopy. These findings would suggest that the projections are tetramers of IP3 receptor molecules and could be used as a morphological marker for the smooth ER in Purkinje cells, which spreads from the soma to the axon and dendrite, up to the tips including the spines. In Purkinje cells tubular smooth ER runs freely in a serpentine fashion or are intertwined to make large membraneous tangles without forming cisternal stacks. It is highly probable that the ER cisternal stacks do not exist naturally in Purkinje cells but are formed artificially during the various procedures for chemical fixation. (+info)
The neuron-specific K-Cl cotransporter, KCC2. Antibody development and initial characterization of the protein.
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The neuron-specific K-Cl cotransporter (KCC2) is hypothesized to function as an active Cl- extrusion pathway important in postsynaptic inhibition mediated by ligand-gated anion channels, like gamma-aminobutyric acid type A (GABAA) and glycine receptors. To understand better the functional role of KCC2 in the nervous system, we developed polyclonal antibodies to a KCC2 fusion protein and used these antibodies to characterize and localize KCC2 in the rat cerebellum. The antibodies specifically recognized the KCC2 protein which is an approximately 140-kDa glycoprotein detectable only within the central nervous system. The KCC2 protein displayed a robust and punctate distribution in primary cultured retinal amacrine cells known to form exclusively GABAAergic synapses in culture. In immunolocalization studies, KCC2 was absent from axons and glia but was highly expressed at neuronal somata and dendrites, indicating a specific postsynaptic distribution of the protein. In the granule cell layer, KCC2 exhibited a distinct colocalization with the beta2/beta3-subunits of the GABAA receptor at the plasma membrane of granule cell somata and at cerebellar glomeruli. KCC2 lightly labeled the plasma membrane of Purkinje cell somata. Within the molecular layer, KCC2 exhibited a distinctly punctate distribution along dendrites, indicating it may be highly localized at inhibitory synapses along these processes. The distinct postsynaptic localization of KCC2 and its colocalization with GABAA receptor in the cerebellum are consistent with the putative role of KCC2 in neuronal Cl- extrusion and postsynaptic inhibition. (+info)
Brain-derived neurotrophic factor mediates the anti-apoptotic effect of NMDA in cerebellar granule neurons: signal transduction cascades and site of ethanol action.
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Cerebellar granule neurons cultured in medium containing a physiological concentration of KCl (5 mM) undergo apoptosis. The cells can be rescued by the in vitro addition of NMDA. The protective effect of NMDA is thought to reflect the in vivo innervation of developing cerebellar granule neurons by glutamatergic afferents. In the current work, we investigated the mechanism of the anti-apoptotic (protective) effect of NMDA. NMDA treatment reduced caspase-3-like activity in cerebellar granule neurons, and the time course and concentration dependence of the protective effect of NMDA mirrored the ability of NMDA to induce brain-derived neurotrophic factor (BDNF) expression. Furthermore, a Trk receptor antagonist, K252a, as well as a blocking antibody to BDNF, attenuated the protective effects of both NMDA and BDNF. These results suggest that NMDA-induced BDNF expression mediates the anti-apoptotic effect of NMDA. The protective effects of NMDA and BDNF were reduced by inhibitors of the phosphatidylinositol 3'-OH kinase (PI 3-kinase) signal transduction cascade (wortmannin and LY29004) but not by a MAP kinase kinase (MEK) inhibitor (PD98059) or a protein kinase A inhibitor (Rp-cAMPS). BDNF increased phosphorylation of Akt, a target of PI 3-kinase, and NMDA also induced Akt phosphorylation, but only after an exposure that was long enough to induce BDNF expression. Furthermore, ethanol, which interferes with NMDA receptor function, inhibited the NMDA-induced increase in BDNF levels but did not block the protective effect of BDNF. These findings further support the role of BDNF in the anti-apoptotic effect of NMDA in cerebellar granule neurons and suggest that the NMDA-BDNF interaction may play a key role in in vivo cerebellar granule neuron development, as well as in the deleterious effects of ethanol on the developing cerebellum. (+info)
Afferent-target cell interactions in the cerebellum: negative effect of granule cells on Purkinje cell development in lurcher mice.
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Lurcher (Lc) is a gain-of-function mutation in the delta2 glutamate receptor gene that results in a large, constitutive inward current in the cerebellar Purkinje cells of +/Lc mice. +/Lc Purkinje cells fail to differentiate fully and die during postnatal development. In normal mice, interactions with granule cells promote Purkinje cell dendritic differentiation. Partial destruction of the granule cell population in young +/Lc mice by x irradiation resulted in a significant increase in Purkinje cell dendritic growth and improved cytoplasmic structure but did not prevent Purkinje cell death. These results indicate two components to Purkinje cell abnormalities in +/Lc mice: a retardation/blockade of dendritic development that is mediated by interactions with granule cells and the death of the cell. Thus, the normal trophic effects of granule cell interaction on Purkinje cell development are absent in the +/Lc cerebellum, suggesting that granule cells are powerful regulators of Purkinje cell differentiation. (+info)
Processing of ARIA and release from isolated nerve terminals.
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The neuromuscular junction is a specialized synapse in that every action potential in the presynaptic nerve terminal results in an action potential in the postsynaptic membrane, unlike most interneuronal synapses where a single presynaptic input makes only a small contribution to the population postsynaptic response. The postsynaptic membrane at the neuromuscular junction contains a high density of neurotransmitter (acetylcholine) receptors and a high density of voltage-gated Na+ channels. Thus, the large acetylcholine activated current occurs at the same site where the threshold for action potential generation is low. Acetylcholine receptor inducing activity (ARIA), a 42 kD protein, that stimulates synthesis of acetylcholine receptors and voltage-gated Na+ channels in cultured myotubes, probably plays the same roles at developing and mature motor endplates in vivo. ARIA is synthesized as part of a larger, transmembrane, precursor protein called proARIA. Delivery of ARIA from motor neuron cell bodies in the spinal cord to the target endplates involves several steps, including proteolytic cleavage of proARIA. ARIA is also expressed in the central nervous system and it is abundant in the molecular layer of the cerebellum. In this paper we describe our first experiments on the processing and release of ARIA from subcellular fractions containing synaptosomes from the chick cerebellum as a model system. (+info)