Diffusion restriction in the corticospinal tract and the corpus callosum of term neonates with hypoxic-ischemic encephalopathy.

BACKGROUND: Diffusion-weighted imaging performed shortly after brain injury has been shown to facilitate visualization of acute corticospinal tract injury known as "pre-Wallerian degeneration." OBJECTIVE: The aim of this study was to determine whether diffusion restriction in the corticospinal tract and corpus callosum occurs within the first 2 weeks after birth in neonates with neonatal hypoxic-ischemic encephalopathy. MATERIALS AND METHODS: We enrolled a consecutive series of 66 infants diagnosed with hypoxic-ischemic encephalopathy who underwent MRI. We evaluated diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) values to assess the presence of restricted diffusion in the corticospinal tract and corpus callosum. Next, we compared ADC values in the corticospinal tract and in the splenium and genu of the corpus callosum of infants with abnormal pattern on MRI with those of control infants, who showed a normal pattern on MRI. We attempted to follow all infants with hypoxic-ischemic encephalopathy until 18 months of age and assess them using a standardized neurologic examination. RESULTS: After exclusions, we recruited 25 infants with abnormal MRI and 20 with normal MRI (controls). Among these 45 neonates, pre-Wallerian degeneration was visualized in the corticospinal tract in 10 neonates and in the corpus callosum in 12. The ADC values in the corticospinal tract in the first week were significantly lower than they were in the second week. Infants with pre-Wallerian degeneration in the corticospinal tract showed an unfavorable outcome. CONCLUSION: Pre-Wallerian degeneration was visualized in the corticospinal tract and corpus callosum and was associated with extensive brain injury caused by hypoxic-ischemic encephalopathy. The changes in signal were observed to evolve over time within the first 2 weeks. The clinical outcome of infants having pre-Wallerian degeneration in the corticospinal tract was unfavorable.

Morphological changes in the pons and cerebellum during the first two weeks in term infants with pontine and cerebellar injury and profound neonatal asphyxia.

BACKGROUND: The morphological changes in the pons and cerebellum of neonates experiencing profound asphyxia in the early period of life remain to be clarified. PURPOSE: To assess the changes in the size of the pons and cerebellum during the first two weeks of life in term neonates with pontine and cerebellar injury caused by hypoxic-ischemic encephalopathy in comparison with a control group. MATERIAL AND METHODS: Two groups were investigated: a group with pontine/cerebellar injury (PCI) (n = 10) demonstrated by magnetic resonance imaging (MRI) diffusion-weighted imaging; and a control group without PCI - focal-multifocal white matter injury and a normal pattern (n = 24). The anteroposterior diameter (APD) and height of the pons and cerebellar vermis, and the transverse width of the cerebellum were measured twice in the first and second weeks of life. Differences between the groups were analyzed statistically using paired and unpaired Student's t-test at a significance level of P < 0.05. RESULTS: In the PCI group, the pontine APD and cerebellar vermian height were significantly decreased in the second week. An increase of pons and cerebellar size was evident during the first two weeks of life in the control groups. CONCLUSION: Infants with PCI and profound asphyxia show rapid decreases in pontine APD and cerebellar vermian height within the first two weeks of life.

Diffusion Restriction in the Optic Radiation of Term Neonates With Hypoxic-Ischemic Encephalopathy Demonstrated by Magnetic Resonance Imaging (MRI).

OBJECTIVE: There has been no previous report of diffusion restriction in the optic radiation of term neonates with hypoxic-ischemic encephalopathy. Here, using diffusion-weighted magnetic resonance imaging (MRI), we assessed diffusion restriction in the optic radiation within the first 2 weeks of life and estimated signal changes and the apparent diffusion coefficient in the optic radiation and lateral geniculate body using T1-weighted MRI. MATERIALS AND METHODS: Forty-five term neonates with hypoxic-ischemic encephalopathy underwent MRI twice during the first 2 weeks of life. Diffusion-weighted imaging and apparent diffusion coefficient were used to evaluate the presence of diffusion restriction in the optic radiation and lateral geniculate body. Apparent diffusion coefficient and T1 signal changes in the optic radiation and lateral geniculate body were also compared with those in 11 control neonates showing a normal pattern on MRI. RESULTS: Diffusion restriction in the optic radiation was observed in 29% (13/45) of the hypoxic-ischemic encephalopathy neonates at a median age of 3.5 days (range: 1-9 days). The apparent diffusion coefficient in the optic radiation of affected neonates was significantly reduced in comparison with the controls. In all neonates with optic radiation involvement, increased T1 signal intensity was observed in the optic radiation in the second week, and was also evident in in lateral geniculate body in 8 of those neonates. CONCLUSION: Diffusion restriction in the optic radiation is not rare among term neonates with hypoxic-ischemic encephalopathy, being visualized by diffusion-weighted imaging in the first week of life and also high-intensity T1 signal changes in the second week. This diffusion restriction in the optic radiation might be due to transsynaptic neuronal degeneration.

Wide distribution of central myelin segment along the facial nerve might explain hemifacial spasm with distal nerve compression.

INTRODUCTION: Many researchers have assumed that neurovascular compression of the facial nerve at the site covered by central myelin sheath causes hemifacial spasm. However, some cases do not correspond to this hypothesis. The aim of this study was to clarify the myelin histology in the facial nerve. MATERIALS AND METHODS: Histological analyses were conducted on 134 facial nerves from 67 cadavers. Three dimensions were measured in these sections: the length from the upper border of the medullopontine sulcus to the boundary between the central and peripheral myelin sheath along the anterior side; the length from the detachment point of the brain stem to the boundary along the posterior side; and the length of the transitional zone (TZ), known as the Obersteiner-Redlich zone. RESULTS: Of the 134 facial nerves, 41 were available for study. The length of the central myelin segment ranged from 4.62 to 12.6 mm (mean 8.06 mm; median 7.98 mm) along the anterior side and from 0.00 to 4.58 mm (mean 1.68 mm; median 1.42 mm) along the posterior side of the facial nerve, and the length of the TZ ranged from 0.00 to 2.76 mm (mean 1.51 mm; median 1.42 mm). CONCLUSIONS: In this study, the length of the central myelin segment in the facial nerve was found to be longer than that previously reported.

Pontine and cerebellar injury in neonatal hypoxic-ischemic encephalopathy: MRI features and clinical outcomes.

BACKGROUND: Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of death and disability in infants. Magnetic resonance imaging (MRI) is valuable for predicting the outcome in high-risk neonates. The relationship of pontine and cerebellar injury to outcome has not been explored sufficiently. PURPOSE: To characterize MRI features of pontine and cerebellar injury and to assess the clinical outcomes of these neonates. MATERIAL AND METHODS: The retrospective study included 59 term neonates (25 girls) examined by MRI using 1.5-T scanner in the first two weeks of life between 2008 and 2017. Involvement of the pons and cerebellum was judged as a high signal intensity on diffusion-weighted image (DWI) and a restricted diffusion on an apparent diffusion coefficient (ADC) map. RESULTS: Pontine involvement was observed in the dorsal portion of pons in eight neonates and cerebellar involvement was observed in dentate nucleus (n = 8), cerebellar vermis (n = 3), and hemisphere (n = 1) in 11 neonates. Combined pontine and cerebellar involvement was observed in eight neonates and only cerebellar involvement in three. The pontine and cerebellar injuries were always associated with very severe brain injury including a basal ganglia/thalamus injury pattern and a total brain injury pattern. In terms of clinical outcome, all but four lost to follow-up, had severe cerebral palsy. CONCLUSION: Pontine and cerebellar involvement occurred in the dorsal portion of pons and mostly dentate nucleus and was always associated with a more severe brain injury pattern as well as being predictive of major disability.

Varying length of central myelin along the trigeminal nerve might contribute to trigeminal neuralgia.

Several studies have suggested that vascular compression of more distal portions of the trigeminal nerve (Vth cranial nerve: VN) may cause trigeminal neuralgia (TN). However, neurosurgeons performing microvascular decompression intraoperatively cannot identify which type of myelin is being compressed by blood vessels. The aim of this study was to clarify the histological anatomy of central and peripheral myelin in the human VN. Histological analyses were conducted using photomicrographs from 134 cisternal segments of the VN from the brains of 67 cadavers. The three dimensions of the VN were measured in these sections: distance from the point at which the lateral-most pontine VN merges with the boundary between central and peripheral myelin (line-a), distance along the medial aspect (line-b), and the length of the transitional zone (TZ), known as the Obersteiner-Redlich zone. Twenty-nine of 134 VNs were available for study. The length of central myelin ranged from 0.69 to 8.66 mm (mean, 3.56 mm; median, 3.10 mm) along the lateral aspect and from 0.36 to 5 mm (mean, 1.81 mm; median, 1.40 mm) along the medial aspect of the VN. The length of the TZ ranged from 0.31 to 3.37 mm (mean, 1.75 mm; median, 1.63 mm). We report here, for the first time, that some individuals had much longer spans of central myelin than those reported previously. Some cases of TN may thus be caused by vascular compression of VN peripheral myelin, especially in cases where central myelin is extended to an unprecedented degree. Clin. Anat. 32:541-545, 2019. © 2019 Wiley Periodicals, Inc.

N-ethylmaleimide-sensitive factor interacts with the serotonin transporter and modulates its trafficking: implications for pathophysiology in autism.

BACKGROUND: Changes in serotonin transporter (SERT) function have been implicated in autism. SERT function is influenced by the number of transporter molecules present at the cell surface, which is regulated by various cellular mechanisms including interactions with other proteins. Thus, we searched for novel SERT-binding proteins and investigated whether the expression of one such protein was affected in subjects with autism. METHODS: Novel SERT-binding proteins were examined by a pull-down system. Alterations of SERT function and membrane expression upon knockdown of the novel SERT-binding protein were studied in HEK293-hSERT cells. Endogenous interaction of SERT with the protein was evaluated in mouse brains. Alterations in the mRNA expression of SERT (SLC6A4) and the SERT-binding protein in the post-mortem brains and the lymphocytes of autism patients were compared to nonclinical controls. RESULTS: N-ethylmaleimide-sensitive factor (NSF) was identified as a novel SERT-binding protein. NSF was co-localized with SERT at the plasma membrane, and NSF knockdown resulted in decreased SERT expression at the cell membranes and decreased SERT uptake function. NSF was endogenously co-localized with SERT and interacted with SERT. While SLC6A4 expression was not significantly changed, NSF expression tended to be reduced in post-mortem brains, and was significantly reduced in lymphocytes of autistic subjects, which correlated with the severity of the clinical symptoms. CONCLUSIONS: These data clearly show that NSF interacts with SERT under physiological conditions and is required for SERT membrane trafficking and uptake function. A possible role for NSF in the pathophysiology of autism through modulation of SERT trafficking, is suggested.

Enzymes in the glutamate-glutamine cycle in the anterior cingulate cortex in postmortem brain of subjects with autism.

BACKGROUND: Accumulating evidence suggests that dysfunction in the glutamatergic system may underlie the pathophysiology of autism. The anterior cingulate cortex (ACC) has been implicated in autism as well as in glutamatergic neurotransmission. We hypothesized that alterations in the glutamate-glutamine cycle in the ACC might play a role in the pathophysiology of autism. METHODS: We performed Western blot analyses for the protein expression levels of enzymes in the glutamate-glutamine cycle, including glutamine synthetase, kidney-type glutaminase, liver-type glutaminase, and glutamate dehydrogenases 1 and 2, in the ACC of postmortem brain of individuals with autism (n = 7) and control subjects (n = 13). RESULTS: We found that the protein levels of kidney-type glutaminase, but not those of the other enzymes measured, in the ACC were significantly lower in subjects with autism than in controls. CONCLUSION: The results suggest that reduced expression of kidney-type glutaminase may account for putative alterations in glutamatergic neurotransmission in the ACC in autism.

CLP36 and RIL recruit α-actinin-1 to stress fibers and differentially regulate stress fiber dynamics in F2408 fibroblasts.

CLP36 is a member of the ALP/Enigma protein family and has been shown to be localized to stress fibers in various cells. We previously reported that depletion of CLP36 caused loss of stress fibers in BeWo choriocarcinoma cells, but it remains unclear how CLP36 contributes to stress fiber formation. In this study, we generated CLP36-depleted F2408 fibroblasts and found that stress fibers showed abnormal non-oriented organization in these cells. In addition to CLP36, F2408 cells contained RIL, another ALP/Enigma protein, and we demonstrated that RIL could compensate for the role of CLP36 in stress fiber formation. CLP36 and RIL form a complex with α-actinin-1 and palladin. We found a strong correlation between loss of CLP36/RIL and failure of α-actinin-1 or palladin to localize on stress fibers. In addition, time lapse observation revealed that incorporation of RIL stabilizes stress fibers and that CLP36 influences the dynamic architecture of these fibers. Our findings indicate that CLP36 and RIL have a redundant role in the formation of stress fibers, but have different effects on stress fiber dynamics in F2408 cells.

[One-year longitudinal change in parameters of myopic school children trained by a new accommodative training device--uncorrected visual acuity, refraction, axial length, accommodation, and pupil reaction].

PURPOSE: School children with myopia were trained using a visual stimulation device that generated an isolated blur stimulus on a visual target, with a constant retinal image size and constant brightness. Uncorrected visual acuity, cycloplegic refraction, axial length, dynamic accommodation and papillary reaction were measured to investigate the effectiveness of the training. SUBJECTS AND METHODS: There were 45 school children with myopia without any other ophthalmic diseases. The mean age of the children was 8.9 +/- 2.0 years (age range; 6-16)and the mean refraction was -1.56 +/- 0.58 D (mean +/- standard deviation). As a visual stimulus, a white ring on a black background with a constant ratio of visual target size to retinal image size, irrespective of the distance, was displayed on a liquid crystal display (LCD), and the LCD was quickly moved from a proximal to a distal position to produce an isolated blur stimulus. Training with this visual stimulus was carried out in the relaxation phase of accommodation. Uncorrected visual acuity, cycloplegic refraction, axial length, dynamic accommodation and pupillary reaction were investigated before training and every 3 months during the training. RESULTS: Of the 45 subjects, 42 (93%) could be trained for 3 consecutive months, 33 (73%) for 6 months, 23 (51%) for 9 months, and 21 (47%) for 12 months. The mean refraction decreased by 0.83 +/- 0.56 D (mean +/- standard deviation) and the mean axial length increased by 0.47 +/- 0.16 mm at 1 year, showing that the training bad some effect in improving the visual acuity. In the tests of the dynamic accommodative responses, the latency of the accommodative-phase decreased from 0.4 +/- 0.2 sec to 0.3 +/- 0.1 sec at 1 year, the gain of the accommodative-phase improved from 69.0 +/- 27.0% to 93.3 +/- 13.4%, the maximum speed of the accommodative-phase increased from 5.1 +/- 2.2 D/sec to 6.8 +/- 2.2 D/sec and the gain of the relaxation-phase significantly improved from 52.1 +/- 26.0% to 72.7 +/- 13.7% (corresponding t-test, p < 0.005). No significant changes were observed in the pupillary reaction. CONCLUSION: The training device was useful for improving the accommodative functions and accommodative excess, suggesting that it may be able to suppress the progression of low myopia, development of which is known to be strongly influenced by environmental factors.

Alteration of plasma glutamate and glutamine levels in children with high-functioning autism.

BACKGROUND: It has recently been hypothesized that hyperglutamatergia in the brain is involved in the pathophysiology of autism. However, there is no conclusive evidence of the validity of this hypothesis. As peripheral glutamate/glutamine levels have been reported to be correlated with those of the central nervous system, the authors examined whether the levels of 25 amino acids, including glutamate and glutamine, in the platelet-poor plasma of drug-naïve, male children with high-functioning autism (HFA) would be altered compared with those of normal controls. METHODOLOGY/PRINCIPAL FINDINGS: Plasma levels of 25 amino acids in male children (N = 23) with HFA and normally developed healthy male controls (N = 22) were determined using high-performance liquid chromatography. Multiple testing was allowed for in the analyses. Compared with the normal control group, the HFA group had higher levels of plasma glutamate and lower levels of plasma glutamine. No significant group difference was found in the remaining 23 amino acids. The effect size (Cohen's d) for glutamate and glutamine was large: 1.13 and 1.36, respectively. Using discriminant analysis with logistic regression, the two values of plasma glutamate and glutamine were shown to well-differentiate the HFA group from the control group; the rate of correct classification was 91%. CONCLUSIONS/SIGNIFICANCE: The present study suggests that plasma glutamate and glutamine levels can serve as a diagnostic tool for the early detection of autism, especially normal IQ autism. These findings indicate that glutamatergic abnormalities in the brain may be associated with the pathobiology of autism.

CLP36 interacts with palladin in dorsal root ganglion neurons.

CLP36, a member of the alpha-actinin-associated LIM protein (ALP)/enigma protein family, plays a role in neurite outgrowth in the peripheral nervous system. However, the underlying molecular mechanisms are not known. In this study, we performed yeast two-hybrid screening of an E18 mouse whole-body cDNA library with CLP36 as the bait and isolated palladin as a CLP36-binding protein. Palladin is an actin-binding protein and it was shown to have a role in the extension of cortical neurons. A coimmunoprecipitation study showed that CLP36 and palladin formed a complex in the dorsal root ganglion (DRG). In addition, CLP36 and palladin were colocalized in the neurites and cell bodies of primary DRG neurons. Furthermore, sciatic nerve transection increased the expression of both CLP36 and palladin mRNAs in DRG neurons, with the increase in CLP36 mRNA being more prominent. This implies that CLP36 has a more specific role in nerve regeneration than palladin. Our results suggest that CLP36 may interact with palladin to influence neurite outgrowth during sciatic nerve regeneration.

Characterization of CLP36/Elfin/PDLIM1 in the nervous system.

CLP36, one of the alpha-Actinin Associated LIM Protein (ALP)/Enigma family proteins, has a wide tissue distribution, but little is known about its expression and role in the nervous system. We show here that CLP36 is expressed in sensory ganglia but not in the CNS of adult rats. In primary dorsal root ganglion (DRG) neurons, CLP36 is distributed in the soma and neurites with enrichment in the growth cones. CLP36 forms a complex with alpha-actinin and is localized to actin cytoskeleton. To examine the role of CLP36 in neuronal cells, we transfected PC12 cells with a series of CLP36 deletion mutants and found that over-expression of CLP36 PDZ domain affects neurite outgrowth. Reduction of CLP36 function in PC12 cells by RNA interference (RNAi) induced lamellipodial protrusions around cell periphery and activated growth-cone movements, resulting in an increase in the length and number of neurites. Similarly, inhibition of CLP36 in primary DRG neurons increased the rate of neurite-bearing cells. We also found that CLP36 is up-regulated in DRG neurons and facial motoneurons after nerve injury. These findings suggest that CLP36 serves as a scaffold to form a multiprotein complex that regulates actin cytoskeleton dynamics and plays a role in controlling neurite outgrowth.

The PDZ-LIM protein CLP36 is required for actin stress fiber formation and focal adhesion assembly in BeWo cells.

CLP36 belongs to the ALP subfamily of PDZ-LIM proteins and has a PDZ domain at its N-terminal and a LIM domain at its C-terminal. It has been shown that CLP36 is localized to stress fibers through interaction with alpha-actinin, but its function is still unclear. To investigate the role of CLP36 in stress fibers, we suppressed CLP36 expression in BeWo cells by RNAi and examined the phenotypic changes. CLP36-knockdown resulted in cell spreading and the loss of stress fibers and focal adhesions. These changes were reversed by addition of exogenous CLP36, but not by addition of mutant forms of CLP36 that lacked the PDZ or LIM domain. These findings indicate that CLP36 plays a critical role in stress fiber formation and the assembly of focal adhesions in BeWo cells. In addition, the PDZ and LIM domains are both essential for CLP36 to function.

Cyclooxygenase-1 mediates the final stage of morphine-induced delayed cardioprotection in concert with cyclooxygenase-2.

OBJECTIVES: We sought to investigate the time course of morphine-induced delayed cardioprotection and examine the role of cyclooxygenase (COX) in this cardioprotective effect. BACKGROUND: Cyclooxygenase-2 has been shown to be essential for the delayed cardioprotection induced by ischemic preconditioning and delta-opioid agonists. METHODS: Male mice were subjected to 45 min of coronary artery occlusion followed by 120 min of reperfusion. Expressions of COX-2 and COX-1 were assessed by Western blotting, and the myocardial prostaglandin (PG)E2 and 6-keto-PGF(1-alpha) contents were measured using enzyme immunoassays. RESULTS: A powerful infarct-sparing effect appeared 24 and 48 h after morphine preconditioning and faded after 72 h. After 24 h, the anti-infarct effect was associated with enhanced myocardial levels of COX-2, PGE2, and 6-keto-PGF(1-alpha), and no changes in COX-1 protein levels were found. Cardioprotection and increases in PGE2 and 6-keto-PGF(1-alpha) were completely abolished by the COX-2-selective inhibitor NS-398 and the non-selective COX inhibitor indomethacin, whereas the COX-1-selective inhibitor SC-560 had no effect. After 48 h, up-regulation of myocardial PGE2 and 6-keto-PGF(1-alpha) was also observed, and COX-1 expression was enhanced markedly, but only a slight increase in COX-2 expression was apparent. Cardioprotection and the increases in PGE2 and 6-keto-PGF(1-alpha) 48 h after morphine administration were abrogated only by indomethacin, and not by SC-560 or NS-398. CONCLUSIONS: Morphine confers delayed cardioprotection via a COX-dependent pathway; COX-2 is essential for the cardioprotection observed in the initial stage (24 h), whereas, in the final stage (48 h), cardioprotection is mediated by COX-1 in concert with COX-2.

Differential expression of KCC2 accounts for the differential GABA responses between relay and intrinsic neurons in the early postnatal rat olfactory bulb.

The rat olfactory bulb is anatomically immature at birth, and considerable neurogenesis and synaptogenesis are known to take place postnatally. In addition, significant physiological changes have also been reported in this period. For example, granule cell-mediated inhibition following electrical stimulations to the lateral olfactory tract is robust during the first postnatal week, and then decreases abruptly after the second week. However, the mechanism underlying this enhanced inhibition remains to be elucidated. To know the cause of this phenomenon, we investigated the expression patterns of cation-Cl(-) co-transporters (KCC1, KCC2 and NKCC1) mRNAs, which are responsible for the regulation of [Cl(-)](i). In addition, responses to gamma-aminobutyric acid (GABA) were measured by gramicidin-perforated patch-clamp recordings and Ca(2+) imaging using fura-2. We found that in the early postnatal period, mitral cells expressing KCC2 mRNA were inhibited by GABA, while granule cells lacking KCC2 mRNA expression were depolarized or excited by GABA. These results indicate that transient GABA-mediated excitation on granule cells might be the main cause of the enhanced inhibition on mitral cells, and suggest that these differential GABA responses between relay and intrinsic neurons play pivotal roles in the early postnatal rat olfactory bulb.

[Long-term clinical course of laser in situ keratomileusis--two year follow-up].

PURPOSE: To evaluate the cases that were treated with laser in situ keratomileusis (LASIK) and who were follwed up for a full 2-year period without fail. MATERIALS AND METHODS: LASIK was performed in 62 eyes of 35 patients between June 1997 and March 1999. Mean age was 29.1 years and the preoperative mean spherical equivalent refraction was -6.90 +/- 2.49 (mean +/- standard deviation) diopter (D). Five aspects were studied as follows. RESULTS: 1. SAFETY: 26 eyes (41.9%) gained 1 line or more in best corrected visual acuity. Twenty eyes (32.3%) were unchanged. Sixteen eyes(25.8%) lost 1 line. No eye lost 2 lines or more. The safety index was 1.04. 2. EFFICACY: The efficacy index was 0.85. 3. Predictability: Forty-eight eyes (77.4%) were predictable within +/- 0.5 D, and 55 eyes (88.7%) were within +/- 1.0 D. 4. Stability: Manifest refraction was relatively stable after 3 months. 5. Complication: No complications were experienced. CONCLUSIONS: Our 2-year follow-up showed that postoperatively LASIK was safe and effective.

The differential expression patterns of messenger RNAs encoding Nogo-A and Nogo-receptor in the rat central nervous system.

Nogo-A and Nogo-receptor have been considered to play pivotal roles in controlling axonal regeneration and neuronal plasticity. We investigated the total distribution of Nogo-A and Nogo-receptor mRNAs in the adult rat central nervous system using in situ hybridization histochemistry. Nogo-A is abundantly expressed in both neurons and oligodendrocytes throughout the central nervous system. Interestingly, we could not find any neuron which lacks Nogo-A mRNA expression, indicating that Nogo-A mRNA is universally expressed in all neurons. In contrast, Nogo-R mRNA expression was very restricted. Nogo-R mRNA was expressed in the olfactory bulb, hippocampus, tentia tecta, some amygdala nuclei, cerebral cortex, some thalamic nuclei, medial habenular, whereas we could not detect it in the other regions. Interestingly, we did not detect Nogo-R mRNA in monoaminergic neurons, which are known to have high regenerative capacity, in the substantia nigra, ventral tegmental area, locus caeruleus, and raphe nuclei. In addition, although neurons in the reticular thalamus and cerebellar nuclei are also known to show high capacity for regeneration, Nogo-R mRNA was not detected there. These data indicate that Nogo-A and Nogo-R mRNAs were differentially expressed in the central nervous system, and suggest that the lack of Nogo-R expression in a given neuron might be necessary to keep its high regenerative capacity.

Synectin in the nervous system: expression pattern and potential as a binding partner of neurotrophin receptors.

To assess the potential for functional interaction between synectin and neurotrophin receptors (Trk receptors) in the nervous system, we characterized synectin expression in the rat brain. Synectin is widely expressed in the brain and its expression levels are regulated both temporally and spatially, correlating with those of Trk receptors. Biochemical studies indicated that synectin interacts with TrkB but not with TrkC in the developing brain. We also found that axotomized motoneurons upregulate synectin mRNA expression as well as TrkB mRNA. These data suggest that synectin plays a role in neural development and regeneration in association with TrkB.