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Biomedical subjects

Junichi Kuratsu

Publications and source records attributed to Junichi Kuratsu.

4 recordsLinked to original sources

Neurofibromatosis type I tumor suppressor neurofibromin regulates neuronal differentiation via its GTPase-activating protein function toward Ras.

Neurofibromin, the neurofibromatosis type 1 (NF1) gene product, contains a central domain homologous to a family of proteins known as Ras-GTPase-activating proteins (Ras-GAPs), which function as negative regulators of Ras. The loss of neurofibromin function has been thought to be implicated in the abnormal regulation of Ras in NF1-related pathogenesis. In this study, we found a novel role of neurofibromin in neuronal differentiation in conjunction with the regulation of Ras activity via its GAP-related domain (GRD) in neuronal cells. In PC12 cells, time-dependent increases in the GAP activity of cellular neurofibromin (NF1-GAP) were detected after NGF stimulation, which were correlated with the down-regulation of Ras activity during neurite elongation. Interestingly, the NF1-GAP increase was due to the induction of alternative splicing of NF1-GRD type I triggered by the NGF-induced Ras activation. Dominant-negative (DN) forms of NF1-GRD type I significantly inhibited the neurite extension of PC12 cells via regulation of the Ras state. NF1-GRD-DN also reduced axonal and dendritic branching/extension of rat embryonic hippocampal neurons. These results demonstrate that the mutual regulation of Ras and NF1-GAP is essential for normal neuronal differentiation and that abnormal regulation in neuronal cells may be implicated in NF1-related learning and memory disturbance.

Alternative Splicing↗

Neuronal responses of the rat amygdala during extinction and reassociation learning in elementary and configural associative tasks.

To investigate functional heterogeneity within the amygdala in appetitive conditioned instrumental behaviours, neuronal activity was recorded from the amygdala of behaving rats during learning and discrimination of conditioned sensory stimuli associated with or without reinforcement [sucrose solution, intracranial self-stimulation (ICSS)]. Sensory stimuli included auditory (tone), visual (light) and configural (simultaneous presentation of tone and light) stimuli. The rat was trained to lick a spout protruded close to its mouth just after a conditioned sensory stimulus to obtain a reward. Of the 609 neurons recorded from the amygdala and amygdalostriatal transition area, 154 responded to one or more sensory stimuli. The 62 amygdalar neurons responded strongly to certain conditioned sensory stimuli associated with rewards. Of these 62 neurons, 45 were tested with the extinction trials. Responses of 31 neurons to conditioned stimuli were finally extinguished, and those of the remaining 14 were not extinguished. Furthermore, responses of 26 of these 31 neurons resumed in the relearning trials (plastic neurons), suggesting that these sensory responses were associative rather than just responses to physical properties of the stimuli. These plastic neurons were located mainly in the basolateral nucleus of the amygdala, and responses of the plastic neurons were correlated with behavioural responses. These results suggest that the basolateral nucleus is crucial in associative learning between sensory information and affective significance for behavioural outputs in appetitive conditioned instrumental behaviours.

Acoustic Stimulation↗

Retrograde cortical and deep venous drainage in patients with intracranial dural arteriovenous fistulas: comparison of MR imaging and angiographic findings.

BACKGROUND AND PURPOSE: We assessed MR imaging, specifically contrast-enhanced three-dimensional (3D) magnetization-prepared rapid gradient-echo (MP-RAGE), in evaluating retrograde venous drainage in patients with intracranial dural arteriovenous fistulas (dAVFs) that may result in catastrophic venous infarction or hemorrhage. METHODS: Twenty-one patients with angiographically proved dAVFs underwent nonenhanced spin-echo (SE) and fast SE imaging, 3D fast imaging with steady-state precession, and enhanced SE and 3D MP-RAGE imaging. Retrograde venous drainage was categorized as cerebral cortical, deep cerebral, posterior fossa medullary, ophthalmic, or spinal venous. We assessed retrograde venous drainage and graded its severity. MR imaging and angiographic severities were correlated. Sensitivity, specificity, and accuracy were calculated to evaluate the diagnostic utility of each technique compared with conventional angiography. We retrospectively correlated angiograms and MR images. RESULTS: Enhanced 3D MP-RAGE and T1-weighted SE images had higher diagnostic accuracy higher than nonenhanced images, especially when retrograde drainage involved cerebral cortical, posterior fossa, and spinal veins. Correlation of severity for enhanced MP-RAGE images and enhanced T1-weighted images with angiograms was good to excellent and better than that with nonenhanced images. All sequences had low diagnostic accuracy when drainage was via deep cerebral veins. On retrospective review, 3D MP-RAGE images showed two thrombotic inferior petrosal sinuses. CONCLUSION: Enhanced MR images were superior to nonenhanced images in assessing retrograde venous drainage in intracranial dAVFs. Enhanced 3D MP-RAGE is superior to enhanced T1-weighted SE imaging for determining the route and severity of venous reflux because of its increased spatial resolution and ability to contiguously delineate the venous system.

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