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Shigeru Ozaki

Publications and source records attributed to Shigeru Ozaki.

11 recordsLinked to original sources

Runx1 selectively regulates cell fate specification and axonal projections of dorsal root ganglion neurons.

Runx1-deficient mice die around embryonic day 11.5 due to impaired hematopoiesis. This early death prevents the analysis of the role of Runx1 in the development of sensory ganglia. To overcome the early embryonic lethality, we adopted a new approach to utilize transgenic Runx1-deficient mice in which hematopoietic cells are selectively rescued by Runx1 expression under the control of GATA-1 promoter. In Runx1-deficient mice, the total number of dorsal root ganglion (DRG) neurons was increased, probably because of an increased proliferative activity of DRG progenitor cells and decreased apoptosis. In the mutant DRG, TrkA-positive neurons and peptidergic neurons were increased, while c-ret-positive neurons were decreased. Axonal projections were also altered, in that both central and peripheral projections of CGRP-positive axons were increased. In the dorsal horn of the spinal cord, projections of CGRP-positive axons expanded to the deeper layer, IIi, from the normal terminal area, I/IIo. Our results suggest that Runx1 is involved in the cell fate specification of cutaneous neurons, as well as their projections to central and peripheral targets.

Animals↗

Characteristics of methylphenidate dependence syndrome in psychiatric hospital settings.

The characteristics of methylphenidate (MPD) cases reported in a nationwide mental hospital survey on substance-related psychiatric disorders are studied compared to methamphetamine cases. Although the two groups did not differ in terms of age and sex, the MPD group revealed longer educational histories and lower antisocial traits. About half of the MPD group had a history of methamphetamine use and 30% had used the substance as the initial substance of abuse. They exhibited a general tendency toward multiple substance use. These results indicate that a significant number of MPD cases exist who used MPD as a substance alternative to methamphetamine and also suggest that they may potentially have a tendency to develop abuse or dependence. The MPD cases most likely had a psychiatric diagnosis of "Dependence syndrome (F15.2)," according to the ICD-10 guidelines. The SDS scores also indicated a more severe dependence syndrome, particularly psychological dependence, which they may possibly develop more quickly. An abundance of information for MPD abusers to utilize is available through the internet, including the pharmacological properties, such as increased sensation or elation through MPD intake and how and where to easily acquire the substance. They may even forge a prescription to obtain MPD. This behavior can be recognized as "substance-seeking behavior" in behavioral pharmacology terms, accompanied by craving based on psychological dependence on the substance, and can be very difficult to control. Little evidence exists regarding the effectiveness and necessity of MPD as a treatment for depression, and thus MPD prescriptions must be carefully considered by psychiatrists or physicians. The application of MPD as an antidepressant in the health insurance system must be re-examined as well.

Adult↗

Peripheral targets influence sensory-motor connectivity in the neonatal spinal cord: sciatic nerve axotomy in Bax-deficient mice.

In neonatal animals, peripheral nerve axotomy induces cell death in the corresponding dorsal root ganglion neurons and motoneurons, indicating that trophic interactions between these neurons and their targets control neuronal survival at this age. However, axotomy-induced cell death masks the role of peripheral tissues in regulating the central connections between these neurons in neonates. Since we have shown in Bax-deficient mice (Bax-/-) that transection of the sciatic nerve at postnatal day (P) 0 rarely induced apoptosis in motoneurons, we examined whether peripheral nerve axotomy eliminates synaptic connections between group Ia afferents and motoneurons in Bax-/-. After the axotomy, we observed in P7 Bax-/- that many axons survived in the fourth lumber (L4) dorsal root and that primary afferent projections to L4 motor pools also remained. Sciatic nerve stimulation evoked synaptic responses in L4 ventral roots in these mice although the amplitudes were considerably smaller and the onset latencies longer compared with the controls. Our results suggest that the monosynaptic connection between group Ia afferents and motoneurons is morphologically and functionally preserved following axotomy. Peripheral tissues may modulate synaptic connectivity but do not contribute to the maintenance of primary afferent projections in the stretch reflex pathway at an immature stage.

Afferent Pathways↗

[A validation of the applicability of the Severity of Dependence Scale (SDS) in a nationwide mental hospital survey on substance-related psychiatric disorders].

We studied the applicability of the Severity of Dependence Scale (SDS) in a nationwide mental hospital survey on substance-related psychiatric disorders in 2002. The SDS is an easily administered five-item scale used to assess psychological dependence, especially the compulsive use of a wide range of substances. The SDS was translated into Japanese (SDS-J) and administered as a part of a questionnaire to 114 patients with substance-dependence syndrome in the survey. The SDS-J had a good internal consistency as demonstrated by the high Cronbach's alpha (0.76). Principal component analyses (PCA) with varimax rotation on the five items revealed a single-factor solution that accounted for 50.8% of the variance. Pearson's correlation coefficient between each item and total score ranged from 0.68 to 0.76, all of which were significant (p<.01). The total score of the SDS-J and the total number of items and psychological dependence-related items in the diagnostic guideline of dependence syndrome of the ICD-10 had rather low Pearson's correlation coefficients (0.17 and 0.23), but those correlations were significant (p < .05 and p < .01). The PCA for the patients with methamphetamine dependence also revealed a single-factor solution that accounted for 55.0% of the total variance. The results indicate that the SDS-J has satisfactory internal and structural reliability and external criteria validity. It also suggests that the SDS-J might be useful for assessing dependence syndrome in clinical settings in Japan, where those substances having properties of causing particularly severe psychological dependence, such as methamphetamine and solvents, are the most common substances of abuse.

Adult↗

[Current situation of substance abuse/dependence in psychiatric hospital settings].

Over the last several years, Japan has been facing its third epidemic of methamphetamine abuse. Methamphetamine and MDMA are categorized as Amphetamine Type Stimulants (ATS), and abuse of these substances has become a worldwide problem. A nationwide mental hospital survey on substance-related psychiatric disorders in Japan has been conducted since 1987 to clarify the current situation of Japan's substance abuse and dependence. Recent surveys show that methamphetamine and organic solvents are the most common substances of abuse in hospital settings. Fifty-five percent of all the patients included in the latest study in 2002 had psychiatric disorders due to methamphetamine abuse. Forty-five percent of them were diagnosed as having a psychotic disorder, and twenty-five percent had psychotic episodes lasting over six months. According to the psychotic disorder criteria in ICD-10 (F1x.5), the duration of a psychotic episode must not exceed six months. If the criteria are strictly applied to the abusers, they should not be diagnosed as having a psychotic disorder due to methamphetamine use, but as having schizophrenia or some other delusional disorder. However, the study demonstrates that many psychiatrists in Japan recognize methamphetamine user patients with persistent episodes of psychosis as having psychosis due to the substance use. This may reflect differences of diagnostic viewpoint between operational criterion in English-speaking countries and clinical observation of Japanese psychiatrists. In other words, it may reflect the difference between the acute toxic model and chronic toxic model of substance-induced psychiatric disorders. Reconsidering this point further will be productive and interesting. The latest survey also indicated gender differences in psychiatric disorders related to substance use. It revealed that female patients were likely to have more severe dependence syndromes, co-morbid psychiatric disorders, and a history of traumatic life events. It suggests that the substance-related psychiatric problems in female patients are possibly more complex and harder to treat. Treatment programs that focus more on gender differences in these disorders should be developed.

Adolescent↗

The effects of sciatic nerve axotomy on spinal motoneurons in neonatal Bax-deficient mice.

During development, the survival of spinal motoneurons depends on the integrity of the connection to their peripheral targets. Peripheral nerve axotomy induces apoptosis in neonatal neurons supplying axons to the nerve. Bax is known to promote apoptosis among developing neurons. To examine the effect of axotomy on spinal motoneurons in Bax-deficient (Bax-/-) and wild-type neonatal mice (Bax+/+), the sciatic nerve was axotomized on postnatal day (P) 0, and motoneurons in the fourth lumbar (L4) segment were visualized at P7 by acetylcholinesterase (AChE) histochemical staining. Presumably due to the reduction in naturally occurring cell death resulting from the deficiency of Bax, there were about 50% more AChE-positive cells in Bax-/- than in Bax+/+. Motoneurons in the dorsolateral motor pool of L4 project through the sciatic nerve. In Bax+/+, axotomy of the sciatic nerve induced significant cell loss in the pool. Most motoneurons survived such axotomy in Bax-/-, although they appeared atrophic and their AChE expression was decreased. Motoneurons may receive vital support retrogradely from their targets, and loss of such support may lead to hypofunction of spinal motoneurons, as indicated by the reduced production of AChE by axotomized motoneurons and their small size in Bax-/-.

Acetylcholinesterase↗

Runx3 controls the axonal projection of proprioceptive dorsal root ganglion neurons.

Dorsal root ganglion (DRG) neurons specifically project axons to central and peripheral targets according to their sensory modality. The Runt-related genes Runx1 and Runx3 are expressed in DRG neuronal subpopulations, suggesting that they may regulate the trajectories of specific axons. Here we report that Runx3-deficient (Runx3(-/-)) mice displayed severe motor uncoordination and that few DRG neurons synthesized the proprioceptive neuronal marker parvalbumin. Proprioceptive afferent axons failed to project to their targets in the spinal cord as well as those in the muscle. NT-3-responsive Runx3(-/-) DRG neurons showed less neurite outgrowth in vitro. However, we found no changes in the fate specification of Runx3(-/-) DRG neurons or in the number of DRG neurons that expressed trkC. Our data demonstrate that Runx3 is critical in regulating the axonal projections of a specific subpopulation of DRG neurons.

Animals↗

Runx3 is essential for the target-specific axon pathfinding of trkc-expressing dorsal root ganglion neurons.

Dorsal root ganglion (DRG) neurons project their axons to specific target layers in the gray matter of the spinal cord, according to their sensory modality (Neuron 30 (2001), 707; Cell 101 (2000), 485; Neuron 31 (2001), 59; J. Comp. Neurol. 380 (1997), 215; Sensory Neurons, Oxford Univ. Press, New York, 1992, p. 131). Expression of runt-related Runx/AML genes (Mech. Dev. 109 (2001), 413) on subtypes of DRG neurons suggests their involvement in lamina-specific afferent differentiation and maturation. Here we show that Runx3-/- mice display severe limb ataxia and abnormal posture and that most of them die shortly after birth. They show that proprioceptive afferent axons fail to reach the ventral horn and have a smaller dorsal funiculus in their spinal cords. Despite the strong resemblance of this phenotype to that of knockout mice deficient in neurotrophin-3 (NT-3) (Cell 77 (1994), 503; Nature 369 (1994), 658) and its receptor, trkC, (Nature 368 (1994), 249), which show proprioceptive afferent loss through selective neuronal cell death, Runx3-/- mice maintain normal number of TrkC/trkC positive DRG neurons throughout development. Our results suggest that Runx3 controls the target-specific axon pathfinding of trkC-expressing DRG neurons in the spinal cord.

Animals↗