Hideshi Yagi

The white matter of the spinal cord is essential for sensory and motor signaling, and its proper development is crucial for establishing functional neuronal circuits. However, the mechanisms underlying white matter formation remain incompletely understood. We hypothesized that the extracellular matrix, particularly laminins, plays a key role in this process. The spatiotemporal expression patterns of laminins during spinal cord white matter development have not been fully characterized. Here, we examined the distribution and function of laminins during spinal cord development. Laminin 332 localized to the marginal zone of the spinal cord at embryonic days 12 (E12) and 14 (E14), coinciding with periods of extensive axonal growth. Immunohistochemical analysis revealed an increase in glial fibrillary acidic protein (GFAP)‐positive fibers in laminin 332‐enriched regions. Laminin 332 promoted GFAP expression in astrocyte precursor cells, an effect attenuated by integrin α6β4 blockade, suggesting that laminin 332 signals through integrins to support astrocyte maturation. Our findings indicate that laminin 332 not only serves as a structural component of the extracellular matrix but also actively regulates glial differentiation during spinal cord development. Understanding the signaling pathways mediated by laminin 332 may inform therapeutic strategies aimed at enhancing spinal cord regeneration by modulating astrocyte behavior and promoting axonal growth.

Interleukin-18 (IL18) is an inflammatory cytokine that is related to psychiatric disorders such as depression and cognitive impairment. We previously found that IL18 deficiency may cause hippocampal impairment, resulting in depression-like behavioral changes. However, the potential role of IL18 in stressful conditions remains uncertain. In the present study, we examined the effect of IL18 on neural inflammation and stress tolerance during acute stress. Littermate Il18^+/+ and Il18^−/− mice were exposed to a single restraint stress for 6 h, and all assessments were performed 18 h after the mice were released from the restraint. In Il18^−/− mice exposed to acute stress, the immobility times in both the forced swim test and tail suspension test were decreased, although no difference was observed in Il18^+/+ mice. Il1β, Il6, and Tnfα expression levels in the hippocampus of stressed Il18^−/− mice were significantly higher than those in the other groups. Moreover, the numbers of astrocytes and microglia, including those in the active form, were also increased compared with those in other groups. Regarding the molecular mechanism, the HSF5 and TTR genes were specifically expressed in stressed Il18^−/− mice. As a potential treatment, intracerebral administration of IL18 to Il18^−/− mice resulted in partial recovery of changes in behavioral assessments. Our results revealed that IL18-deficient mice were more sensitive and had a longer response to acute stress than that in normal mice. In addition, neural inflammation and augmentation of glucocorticoid signals caused by stress were more intense and remained longer in Il18^−/− mice, resulting in behavioral changes. In conclusion, IL18 might be an indispensable factor that modulates the stress response and maintains balance between neural inflammation and glucocorticoid signaling.

Nerves in the renal parenchyma comprise sympathetic nerves that act on renal arteries and tubules to decrease blood flow and increase primary urine reabsorption, respectively. Synaptic vesicles release neurotransmitters that activate their effector tissues. However, the mechanisms by which neurotransmitters exert individual responses to renal effector cells remain unknown. Here, we investigated the spatial and molecular compositional associations of renal Schwann cells (SC) supporting the nerve terminals in male rats. The nerve terminals of vascular smooth muscle cells (SMCs) enclosed by renal SC processes were exposed through windows facing the effectors with presynaptic specializations. We found that the adrenergic receptors (ARs) α2A, α2C, and β2 were localized in the SMC and the basal side of the tubules, where the nerve terminals were attached, whereas the other subtypes of ARs were distributed in the glomerular and luminal side, where the norepinephrine released from nerve endings may have indirect access to ARs. In addition, integrins α4 and β1 were coexpressed in the nerve terminals. Thus, renal nerve terminals could contact their effectors via integrins and may have a structure, covered by SC processes, suitable for intensive and directional release of neurotransmitters into the blood, rather than specialized structures in the postsynaptic region.

Vibration is detected by mechanoreceptors, including Pacinian corpuscles (PCs), which are widely distributed in the human body including the adventitia of large blood vessels. Although the distribution of PCs around large limb vessels has been previously reported, there remains no consensus on their distribution in the adventitia of the human deep blood vessels in the upper arm. In addition, the physiological functions of PCs located around the deep limb blood vessels remain largely unknown. This study aimed to elucidate detailed anatomical features and physiological function of lamellar sensory corpuscles structurally identified as PCs using the immunohistochemical methods around the deep vessels in the upper arm. We identified PCs in the connective tissue adjacent to the deep vessels in the upper arm using histological analysis and confirmed that PCs are located in the vascular sheath of the artery and its accompanying vein as well as in the connective tissue surrounding the vascular sheath and nerves. PCs were densely distributed on the distal side of deep vessels near the elbow. We also examined the relationship between vascular sound and pulsating sensation to evaluate the PCs functions around deep arteries and veins and found that the vascular sound made by pressing the brachial arteries in the upper arm was associated with the pulsating sensation of the examinee. Our results suggest that PCs, around deep vessels, function as bathyesthesia sensors by detecting vibration from blood vessels.

The essential involvement of phosphoinositides in synaptic plasticity is well-established, but incomplete knowledge of the downstream molecular entities prevents us from understanding their signalling cascades completely. Here, we determined that Phldb2, of which pleckstrin-homology domain is highly sensitive to PIP₃, functions as a phosphoinositide-signalling mediator for synaptic plasticity. BDNF application caused Phldb2 recruitment toward postsynaptic membrane in dendritic spines, whereas PI3K inhibition resulted in its reduced accumulation. Phldb2 bound to postsynaptic scaffolding molecule PSD-95 and was crucial for localization and turnover of PSD-95 in the spine. Phldb2 also bound to GluA1 and GluA2. Phldb2 was indispensable for the interaction between NMDA receptors and CaMKII, and the synaptic density of AMPA receptors. Therefore, PIP₃-responsive Phldb2 is pivotal for induction and maintenance of LTP. Memory formation was impaired in our Phldb2^−/− mice.

Pacinian corpuscles are vibration‐sensing mechanoreceptors that are densely distributed in the dermis of the human hand. Although they are also known to occur in various other regions/structures throughout the human body, including the adventitia of large vessels, their precise distribution and function in arteries remain unclear. In the present study, we identified Pacini‐like lamellar corpuscles (LCs) adjacent to the femoral artery, and investigated their distribution with respect to that structure via a histological analysis. We identified nine LCs that were localized in the connective tissue surrounding the femoral artery and vein. We showed that although their distribution was heterogeneous, they were predominantly concentrated on the dorsal side of the femoral artery. Immunohistochemical analyses revealed that the identified femoral artery LCs exhibited features characteristic of typical LCs located in the dermis of the index finger. Thus, the results of the present study contribute to an improved understanding of the function of femoral artery LCs. Anat Rec, 301:1809–1814, 2018.