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ABSTRACT: The posttranslational conformational conversion of the cellular isoform of prion protein PrP(C) into its scrapie isoform PrP(Sc) is the fundamental process underlying the pathogenesis of prion disease. Based on several transgenic data, it has been postulated that a putative auxiliary factor denoted protein X functions as a molecular chaperone through its unfolding activity of PrP(C) during the formation of PrP(Sc). However, the assumption that protein X therefore exists exclusively in prion diseases appears improbable and thus, it should have some simultaneous physiological role. We, hereby, propose a novel concept - a characteristic role of protein X in supporting a physiological endoproteolytic cleavage of PrP(C). The events corresponding to the formation of the physiologically metabolized PrP(C) or the pathologically transformed PrP(Sc) are mutually exclusive. Amino acid residues that are critical in terms of the target site of protein X for the pathological alteration into PrP(Sc) overlap at the cleavage site. These amino acid residues tend to have a hydrophobic property and are most probably found buried inside the native protein structure. Therefore, a putative molecular chaperone identical to protein X may target the same hydrophobic residues in PrP(C) and work in conjunction with either PrP(Sc) in prion disease or PrP proteases during the physiological state. This postulation may help explain in a relatively simple manner these two mutually exclusive phenomena, viz. the physiological endoproteolytic cleavage of PrP(C) and its pathological conversion into PrP(Sc).
Medical Hypotheses 02/2007; 68(3):670-3. · 1.39 Impact Factor
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ABSTRACT: Using collision tests of orthodromically and antidromically generated spikes, we studied the axonal pathways, axonal projection levels, and soma location of anterior semicircular canal (AC) nerve-activated vestibulospinal neurons in decerebrate cats. AC nerve-activated vestibulospinal neurons (n=74) were mainly located in the ventral portion of the lateral vestibular nuclei and the rostral portion of the descending vestibular nucleus, which is consistent with previous studies. Of these neurons, 15% projected through the ipsilateral (i-) lateral vestibulospinal tract (LVST), 74% projected through the medial vestibulospinal tract (MVST), and 11% projected through the contralateral (c-) LVST. The vast majority (78%) of AC nerve-activated vestibulospinal neurons were activated antidromically only from the cervical segment of the spinal cord; 15% of neurons were activated from the T1 segment and only one neuron was activated from the L3 segment. AC nerve-activated vestibulospinal neurons may primarily target the neck muscles and thus contribute to the vestibulocollic reflex. Most of the c-LVST neurons were also activated antidromically from the oculomotor nucleus, suggesting that they are closely related to the control of combined eye-head movements.
Neuroscience Letters 11/2006; 406(1-2):1-5. · 2.11 Impact Factor
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ABSTRACT: Because of technical obstacles in controlling current spread to adjacent peripheral nerve, eye movements evoked by activation of the otolith organs have not been investigated in detail compared to eye movements evoked by activation of the canal organs. We attempted to solve this problem by applying more sensitive methods using fine needle and strictly controlling stimulus current intensity compare with filed potential for selective stimulation.
Eye movements evoked by selective, unilateral saccular (SAC) nerve stimulation were investigated using both electrooculography (EOG) and video recording in decerebrated cats in the presence or absence of anesthesia. Electrical stimulation was applied to the SAC nerve through implanted acupuncture needles.
In the absence of anesthesia and with stimulus intensities less than (3.1 +/- 2.7) x N(1)T, we found supraduction in both eyes or in either the ipsilateral or contralateral eye of different cats. We observed downward eye movements using a stronger stimulus intensity ((6.2 +/- 2.9)) x N(1)T). The threshold for downward eye movements was significantly greater than that for upward eye movements (P < 0.05). In anesthetized cats, only downward eye movements were observed when stimulus intensities less than 10 x N(1)T ((7.8 +/- 2.3) x N(1)T) were used.
These results confirm the known sacculo-ocular anatomical connections, which are involved predominantly in vertical eye movements. Because the sacculo-ocular connections are relatively weak, the normal supraduction evoked by SAC activation can be easily modified by factors such as level of anesthesia and the method of stimulation.
Auris Nasus Larynx 09/2004; 31(3):220-5. · 0.76 Impact Factor
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ABSTRACT: Axonal pathways, projection levels, and locations of horizontal semicircular canal (HC) nerve-activated vestibulospinal neurons were studied. The HC nerve was selectively stimulated. Vestibulospinal neurons were activated antidromically with four stimulating electrodes, inserted bilaterally into the lateral vestibulospinal tracts (LVST) and medial vestibulospinal tracts (MVST) at the C1/C2 junction. Stimulating electrodes were also positioned in the C3, T1, and L3 segments and in the oculomotor nuclei. Most HC nerve-activated vestibulospinal neurons were located in the ventral portion of the medial, lateral, and the descending nuclei. Among the 157 HC nerve-activated vestibular neurons, 83 were antidromically activated by stimulation at the C1/C2 junction. Of these 83 neurons, axonal pathways of 56 HC nerve-activated vestibulospinal neurons were determined. Most (48/56) of these had axons that descended through the MVST, with the remainder (8 neurons) having axons that descended through the ipsilateral (i-) LVST. Laterality of the axons' trajectories through the MVST was investigated. The majority of vestibulospinal neurons (24/28) with axons descending through the contralateral MVST were also antidromically activated from the oculomotor nucleus, whereas almost all vestibulospinal neurons (19/20) with axons descending through the i-MVST were not. Most HC nerve-activated vestibulospinal neurons were activated antidromically only from the C1/C2 or C3 segments. Only one neuron that was antidromically activated from the T1 segment had an axon that descended through the i-LVST. None of the HC nerve-activated vestibulospinal neurons were antidromically activated from the L3 segment. It is likely that the majority of HC nerve-activated vestibulospinal neurons terminate in the cervical cord and have strong connections with neck motoneurons.
Experimental Brain Research 07/2004; 156(4):478-86. · 2.39 Impact Factor
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ABSTRACT: Eye movements evoked by otolith organ are not well-investigated compare with canal related eye movements due to the technical difficulties. We try to solve this problem by means of our methods.
Eye movements evoked by selective utricular (UT) nerve stimulation were investigated using both electrooculography (EOG) and video recording in decerebrated cats in the presence or absence of anesthesia. Electrical stimulation was applied to the UT nerve through implanted acupuncture needles.
In the absence of anesthesia and with stimulus intensities less than 2.6+/-0.7 x N(1)T, we found ipsilaterally directed horizontal eye movements in both eyes in one cat, abduction in the ipsilateral eye in two cats, and adduction in the contralateral eye in another cat. Other types of eye movements (e.g., supraduction or diagonal eye movements) were observed in both eyes of cats in the absence of anesthesia at a stimulus intensity of 12.2+/-7.6 x N(1)T, an intensity in which current spread to the adjacent nerve could not be ruled out. In the presence of anesthesia, UT nerve stimulation alone failed to evoke horizontal eye movements, but with an intensity 13.8+/-6.4 x N(1)T, supraduction or diagonal eye movements were evoked. UT nerve stimulation at 2-3 x N(1)T facilitated horizontal eye movements induced by ipsilateral abducens (AB) nucleus stimulation or contralateral horizontal canal nerve stimulation.
This is the first report to our knowledge in which UT nerve-evoked horizontal eye movements are documented. These results confirm the known monosynaptic and disynaptic anatomical connections from utricular primary afferents to the ipsilateral AB nucleus neurons.
Auris Nasus Larynx 01/2004; 30(4):341-8. · 0.76 Impact Factor
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ABSTRACT: The morphology of physiologically identified otolith nerve-activated vestibular neurons was investigated using intracellular injections of horseradish peroxidase (HRP). Eleven utricular, 11 saccular and three utricular/saccular nerve-activated vestibular neurons were labeled with HRP. All of these neurons except one were secondary neurons, the exception being a convergent neuron. The labeled neurons were pyramidal, elongated and ovoidal in shape. Most of the labeled cells were medium to large (mean diameter: > or =30 micro m). There was no apparent correlation between morphology and the different types of otolith nerve-activated vestibular neurons. Thus, it seems likely that the functional type of vestibular neurons cannot be presumed on the basis of their morphology alone.
Neuroscience Letters 10/2002; 331(1):37-40. · 2.11 Impact Factor
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ABSTRACT: Axonal pathways, projection levels, conduction velocities, and locations of the cell bodies of saccular nerve-activated vestibulospinal
neurons were studied in decerebrated cats and anesthetized cats, using a collision test of orthodromic and antidromic spikes.
The saccular nerve was selectively stimulated by bipolar tungsten electrodes. Three monopolar electrodes were inserted into
the left and right lateral vestibulospinal tract (LVST) and medial vestibulospinal tract (MVST) of the C1 segment, to determine
the pathway of axons. Three pairs of similar electrodes were positioned bilaterally in the C3–4, T1, and L3 segments to examine
projection levels. Another monopolar electrode was placed in the oculomotor nucleus to determine whether saccular nerve-activated
vestibulospinal neurons have branches ascending to the oculomotor nucleus. Of 145 vestibular neurons orthodromically activated
by stimulation of the saccular nerve, 46 were activated from the C1 segment antidromically. Forty-three were second-order
vestibulospinal neurons and 3 were third-order vestibulospinal neurons. Four saccular nerve-activated vestibulospinal neurons
were also antidromically activated from the oculomotor nucleus. Sixty-three percent of the saccular nerve-activated vestibulospinal
neurons descended through the MVST; one-third of these terminated in the upper cervical segments, one-third reached the lower
cervical segments and the remaining one-third reached the upper thoracic segments. Thirty percent of the saccular nerve-activated
vestibulospinal neurons descended through the ipsilateral LVST; most of these reached the upper thoracic segments. Seven percent
of the saccular nerve-activated vestibulospinal neurons descended through the contralateral vestibulospinal tracts terminating
in the upper cervical segments. Most of the saccular nerve-activated vestibulospinal neurons originated in the caudal part
of the lateral nucleus and rostral part of the descending nucleus.
Experimental Brain Research 09/1997; 116(3):381-388. · 2.39 Impact Factor
