Reinnervation of rat Pacinian corpuscles after nerve crush during the postcritical period of development

Summary The ultrastructure of crural Pacinian corpuscles was examined after sciatic nerve crush performed in 7- to 20-day-old rats, i.e. during the postcritical period of development when the corpuscles no longer degenerate after axotomy but cease growing. The aim of our study was to assess the innervation pattern and structural changes of the corpuscles following transient denervation and subsequent reinnervation during their maturation and growth. Reinnervated corpuscles were examined by electron microscopy from 2.5 months after nerve crush onwards. After sciatic nerve crush at 7 days of age, the corpuscles are mostly reinnervated with multiple axon terminals, each of them enclosed within a newly formed inner core. The axial multiple cores are in part covered by a layer of concentric inner core lamellae and surrounded by a capsule, both structures having survived from the original corpuscle. After nerve crush at 10 days of age, reinnervated Pacinian corpuscles usually contain, in their axial region, a denervated remainder of the original core together with a few regenerated axon terminals enclosed within new inner cores. These axial structures are surrounded by a layer of concentric lamellae of the original core which may accommodate some regenerated terminals. Additional axon terminals with their small inner cores may be found at the outer aspect of the composite core beneath the capsule. When the nerve is crushed in 15-day-old rats, the inner core which is already well developed remains preserved by the time of reinnervation, and regenerating axons grow in between the original lamellae inducing only moderate neoformation of 2–3 lamellar layers which enclose the terminals. After crushing the sciatic nerve in 20-day-old rats, formation of new inner core lamellae is minimal and regenerated terminals become accommodated between the original lamellae of the core as is the case in adult animals. Regeneration of new inner cores and reinnervation of the preserved lamellar structure thus characterize the recovery of Pacinian corpuscles following reinnervation after nerve crush during the postcritical period of their development.     

Multiple axon terminals in reinnervated Pacinian corpuscles of adult rat

Summary The ultrastructure of Pacinian corpuscles localized beneath the crural interosseous membrane was examined two weeks to 18 months after crushing the sciatic nerve in adult rats. The Pacinian inner core and capsule remained preserved during the transient period of denervation. Regenerating axons reached Pacinian corpuscles approximately three weeks after nerve crush. Up to 15 axonal sprouts entered a single corpuscle at the initial stage of reinnervation, but only 1–3 axons increased in size, myelinated and formed axon terminals in the inner core, the excess sprouts being eliminated. Most corpuscles of the crural group were reinnervated by the end of the first month.Three to 19 months after nerve crush, 10% of corpuscles examined were found to be monoaxonal and monoterminal as before the operation; 74% contained multiple terminals; 16% remained denervated. Over half the multiterminal corpuscles were supplied with a single myelinated axon that branched inside the corpuscles; the rest received two or three myelinated axons which formed several terminals. The terminals were distributed at random, usually in the axial region between the lamellae of the inner core. They were cylindrical, with an oval profile; the larger terminals were filled with mitochondria and microtubules at their circumference and contained a core of neurofilaments. Lateral processes of the terminals were filled with vesicles and had membrane specializations as in normal corpuscles. The mean number of terminals in reinnervated corpuscles was 4.07 ± 0.37 (S.E.M.) at three months, and 3.26 ± 0.49 (S.E.M.) 6–18 months after nerve crush. This small decrease was apparently the result of degeneration occasionally observed in some axon terminals at later stages of reinnervation.These experiments thus demonstrate that most rat Pacinian corpuscles become reinnervated with multiple terminals after nerve injury and maintain multiterminal innervation permanently.     

Reinnervation of Pacinian corpuscles by CNS axons after transplantation to the dorsal column: incidence and ultrastructure

Summary We have investigated the capacity of injured axons in the spinal dorsal columns of young adult rats to reinnervate grafted Pacinian corpuscles. A branch of the hindlimb interosseous nerve with a group of crural Pacinian corpuscles attached to it was autotransplanted to the surface of the spinal cord and the nerve stump was implanted into the dorsal column. Two to three months later 16 grafts were removed for examination by light and electron microscopy. By 3 months after transplantation almost all Schwann cell columns of the grafted nerve branch were occupied by regenerated myelinated and unmyelinated axons. Of 41 corpuscles examined by electron microscopy 24 were reinnervated by 1–3 myelinated fibres which gave rise to multiple terminals in the inner core. The remaining corpuscles appeared to be denervated. Only two of the reinnervated corpuscles contained regenerated endings which reiterated the distinct ultrastructure of normal presynaptic terminals of CNS axons, characterized by clusters of lucent vesicles and paramembranous densities. All other corpuscles were reinnervated by terminals which resembled peripheral mechanosensory endings as they contained mitochondria and very few vesicles. One such corpuscle was coinnervated by small terminals filled with large dense cored vesicles. We assume that the majority of grafted Pacinian corpuscles have been reinnervated by dorsal column axons and that the regenerated terminals with the ultrastructure of peripheral mechanosensory endings derive from central axons of primary sensory neurons, which are apparently capable of constructing mechanosensory-like terminals in response to signals from the Pacinian corpuscles. The vesicle-filled endings are probably formed by second order sensory neurons, corticospinal neurons and small peptidergic neurons unable to adjust their terminals to the new target.     

Reinnervation of transplanted Pacinian corpuscles by ventral root axons: Ultrastructure of the regenerated nerve terminals

Summary This study addresses two questions. Can mature, denervated and transplanted Pacinian corpuscles accept innervation from motor axons? If so, does the alien target influence the structural characteristics of the regenerated motor axon terminals? Pacinian corpuscles from the hind leg of young rats, together with a segment of the nerve branch through which they receive their sensory innervation, were autotransplanted to the surface of the spinal cord and the nerve stump anastomosed to the central stump of a transected lumbar ventral root. Between 4 and 5 months later the grafts were studied by electron microscopy. Ventral root axons regenerated through the endoneurial tubes of the grafted nerve to reach the corpuscles, most of which became reinnervated by one to three myelinated fibres. The fibres lost their myelin sheaths before entering the inner core, branched, and gave rise to multiple terminals in the inner core. The regenerated terminals were packed with spherical synaptic vesicles and closely resembled normal motor nerve terminals. Thus motor axons are able to reinnervate Pacinian corpuscles but the structural characteristics of the terminals are apparently not modified by the alien target tissue. This finding contrasts with previous studies, in which it was found that terminals of the central axons of large dorsal root ganglion cells, induced to reinnervate Pacinian corpuscles, displayed the structural characteristics of peripheral sensory endings rather than those of dorsal root terminals in the spinal cord.     

The extracellular matrix of rat pacinian corpuscles: an analysis of its fine structure

The Pacinian corpuscle consists of a sensory axon terminal that is enveloped by two different structures, the inner core and the capsule. Since proteoglycans are extremely water soluble and are extracted by conventional methods for electron microscopy, the current picture of the structural composition of the extracellular matrix in the inner core and the capsule of the Pacinian corpuscle is incomplete. To study the structural composition of the extracellular matrix of the Pacinian corpuscles, cationic dyes (ruthenium red, alcian blue, acridine orange) and tannic acid were applied simultaneously with the aldehyde fixation. The interosseal Pacinian corpuscles of the rat were fixed either in 2% formaldehyde and 1.5% glutaraldehyde, with the addition of one of these cationic dyes or, in Zamboni’s fixative, with tannic acid added. The cationic dyes and tannic acid revealed a different structural pattern of proteoglycans in the extracellular matrix in the inner core and in the capsule of the rat Pacinian corpuscles. The inner core surrounding the sensory axon terminal is a compartment containing proteoglycans that were distributed not only in the extracellular matrix but also in the cytoplasm of the lamellae. In addition, this excitable domain was separated from the capsular fluid by a thick layer of proteoglycans on its surface. An enlarged interlamellar space of the capsule contained large amounts of proteoglycans that were removed by digestion with chondroitinase-ABC. Ruthenium red and alcian blue provided only electron dense granules, probably corresponding to collapsed monomeric proteoglycan molecules. Acridine orange and tannic acid preserved proteoglycans very well and made it possible to visualize them as ”bottlebrush” structures in the electron microscope. These results show that the inner core and the capsule of rat Pacinian corpuscles have different structural patterns of proteoglycans, which are probably involved in different functions. Accepted: 21 May 1999     

Restoration of lamellar structures in adult rat Pacinian corpuscles following their simultaneous freezing injury and denervation

The capsule and inner core are multilamellar auxiliary structures enveloping the axon terminal of the Pacinian corpuscle. The freezing injury of the rat interosseal Pacinian corpuscles induced the destruction of all cellular components while the extracellular matrix including the basal laminae survive the treatment. Simultaneous denervation and the freezing treatment of the Pacinian corpuscles discovered an ability of the basal lamina and other components of the extracellular matrix to stimulate a differentiation of migrated Schwann cells and fibroblasts into multilamellar auxiliary structures. The restoration of inner core and capsule in the Pacinian corpuscles was independent of the presence of sensory axon terminals. The restored lamellar structures of Pacinian corpuscles in long-term surviving rat (4 to 8 months) displayed atrophic changes. The results suggest that the extracellular matrix of rat Pacinian corpuscles may contain molecules that are produced by Schwann cells and fibroblasts during maturation of the multilamellar auxiliary structures. The molecules deposited into the extracellular matrix are able to influence the redifferentiation of multilamellar auxiliary structures from immature cells. Accepted: 30 March 2000     

The development of Pacinian corpuscles

Summary The fine structural development of Pacinian corpuscles on the interosseous membrane of the rat was investigated from day 18 of gestation until 2 months after birth.At the initial stage of development on day 19–20 of gestation, Pacinian corpuscles consist of a cylindrical sensory terminal surrounded by one layer of cells which are apposed to the terminal and send off short lamellar processes towards the axolemma. These presumptive inner core cells accumulate around the terminal in continuation of the Schwann cell sheath, which indicates their Schwann cell origin. Both the inner core cells and their lamellae rapidly increase in number. At birth, the sensory terminal is already enclosed in a rudimentary inner core comprising several layers of loosely arranged lamellae, with cell nuclei accumulated at the outer circumference of the inner core. The sensory terminal sends off axonal processes from random sites on its circumference, and ends as a bulb which projects numerous axonal processes in all directions. The organelle content of the terminal consists of many mitochondria oriented lengthwise among microtubules and neurofilaments; clear and dense core vesicles are found in groups beneath the axolemma and at the bases of axonal processes and branches, whereas the processes themselves contain a microfilamentous network. Numerous coated invaginations and vesicles are found at the axolemma and in the lamellae enclosing the axon, indicating uptake of macromolecules on both sides of the periaxonal cleft. The outer capsule begins to form around the inner core shortly before birth; in neonatal rats, it consists of approximately five attenuated lamellae.During the first postnatal week, the inner core lamellae increase in number, become tightly packed together and concentrically arranged. The bilateral symmetry of the inner core is established 5–12 days after birth, when 2 opposite radial clefts are formed, bisecting the inner core cylinder into 2 corresponding sectors. From the cellular layer of the inner core, cytoplasmic arms penetrate through the radial cleft, giving rise to hemilamellae of one or both sectors. The axonal processes eventually become aligned 2–3 weeks after birth so that they project into the radial clefts, except for the bulbous ultraterminal part from which they project in all directions.During the 2 postnatal months studied, the inner core grows continuously in length, but its diameter remains practically unchanged. The outer capsule grows considerably during this time, as both the number of capsular layers and the spacing between them continue to increase. Pacinian corpuscles are on the average 475.8 ± 10.7 m in length and 220.8 ± 6.3m in diameter by day 60 postnatal, their size having increased about four fold from birth.     

The electron microscopic localization of alkaline phosphatase in Pacinian corpuscles of the cat

The ultrastructural localization of alkaline phosphatase has been studied in Pacinian corpuscles of the cat mesentery by the method of Mayahara et al. (1967) with 3 substrates. As control studies, specimens were incubated in the medium containing L-cysteine (10 mmol) or EDTA (5 mmol). The electron opaque final reaction product was observed on plasmic membranes and in cytoplasm and pinocytotic vesicles of the inner core cells. The precipitate was present also in rough endoplasmic reticulum, multivesicular bodies, and cytoplasmic vacuoles of the inner core lamellae. The axon revealed the positive enzymatic activity in the axolemma and the scattered precipitate was found in axoplasm. The pinocytotic vesicles in the capillary endothelium entering Pacinian corpuscles contained the reaction product, too. The capsule lamellae were devoid of precipitate. Localization of alkaline phosphatase in pinocytotic vesicles of the inner core lamellae and capillary wall support the opinion that this enzyme plays the significant role in the phenomenon of the transport of molecules through inner core lamellae from capillaries to the axon in Pacinian corpuscles.     

Heparan sulfate in human cutaneous Meissner's and Pacinian corpuscles

Heparan sulfate proteoglycans are pericellular/cell surface molecules involved in somatosensory axon guidance in the peripheral nervous system. However, the distribution of heparan sulfate proteoglycans in the extracellular matrix of human cutaneous sensory corpuscles is unknown. Immunohistochemistry and immunofluorescence assays were performed to define the localization of heparan sulfate proteoglycans in human cutaneous Meissner's and Pacinian corpuscles using two anti-heparan sulfate antibodies together with anti-S100 protein, anti-PGP9.5, anti-CD34 (to immunolabel basement membranes, Schwann cells, axon and the intermediate endoneurial layer of Pacinian corpuscles, respectively), anti-Type IV collagen, and anti-chondroitin sulfate antibodies. Heparan sulfate proteoglycans were colocalized with Type IV collagen in Meissner's corpuscles and were located in the outer core lamellae and capsule, but not in the inner core or the intermediate layer, in Pacinian corpuscles. Chondroitin sulfate was observed in the intermediate layer of Pacinian corpuscles but was never colocalized with heparan sulfate proteoglycans. The present results strongly suggest that heparan sulfate proteoglycans are associated with the basement membranes of the lamellar cells in Meissner's corpuscles and with the complex outer core capsule in Pacinian corpuscles. The functional significance of these results, if any, remains to be elucidated.     

Immunocytochemical localization of the neural cell adhesion molecules L1, N-CAM, and J1 in Pacinian corpuscles of the mouse during development, in the adult and during regeneration

Summary The immunocytochemical localization of the neural cell adhesion molecules L1, N-CAM and J1/tenascin was investigated by light and electron microscopical techniques in murine Pacinian corpuscles during development, in the adult and in the regenerating state. In adult corpuscles, L1 was present only at contact sites between the sensory axon and inner core lamellae. From birth, the earliest stage tested, until day 7, L1 was additionally expressed on lamellar processes of the inner core cells. N-CAM was expressed in developing and adult corpuscles on lamellae and somata of the inner and outer core cells at their contact sites but was hardly detectable at contact sites between axolemma and inner core lamellae. J1/tenascin was found only in association with the extracellular material of the inner core, especially with the two radial clefts and the boundary space between inner and outer core. In developing corpuscles, J1/tenascin became detectable on extracellular material with the onset of inner core differentiation at approximately day 2. After transection or crush of the sciatic nerve, L1 disappeared from the corpuscles but reappeared with regrowing axons at contact sites between axonal membranes and inner core cells. At any regenerative stage inner core cells remained L1-negative. In denervated and reinnervated corpuscles the expression pattern of N-CAM and J1/tenascin did not differ from the normal adult. These observations suggest that a sensory organ, the Pacinian corpuscle, differs from the sciatic nerve and the neuromuscular junction in that its expression of adhesion molecules remains the same in the denervated state as in the innervated adult. Furthermore, in the denervated Pacinian corpuscle, adhesion molecule expression does not resemble that of any developmental stage tested. Thus, other cues than regulation of adhesion molecule expression patterns might be involved in the successful reinnervation of sensory corpuscles.     

Chondroitin Sulfate in Human Cutaneous Meissner and Pacinian Sensory Corpuscles

Chondroitin sulfate is a glycosaminoglycan involved in maintaining the morphofunctional properties of the extracellular matrix in peripheral nerves, but its distribution in human sensory corpuscles is unknown despite the role of extracellular matrix in mechanotransduction and axonal guidance. In this study we used immunohistochemistry to analyze the distribution of chondroitin sulfate in human cutaneous Meissner and Pacinian corpuscles. Chondroitin sulfate expression was absent from Meissner corpuscles. In Pacinian corpuscles chondroitin sulfate was found associated to a CD34 positive endoneurial-related layer, interposed between the S100 protein positive inner core cells, and the vimentin positive inner core and outer core-capsule cells. Therefore, the intermediate CD34+/chondroitin sulfate+ intermediate layer present in Pacinian corpuscles isolates the neural segment of the corpuscles (axon and inner core) from the non-neural segments (outer core and capsule). These results suggest a role of chondroitin sulfate in the proper axonal growth and guidance, within the neuronal compartment of the Pacinian corpuscles during development and reinnervation, can be hypothesized. Moreover, a role of CS in mechanotransduction cannot be ruled out. Anat Rec, 302:325–331, 2019. © 2018 Wiley Periodicals, Inc.     

Nerve growth factor receptor immunoreactivity in Meissner and Pacinian corpuscles of the human digital skin

The presence of nerve growth factor receptors (NGFr) in sensory nerve corpuscles of human digital skin, primarily Meissner and Pacinian corpuscles, was investigated immunohistochemically using two monoclonal antibodies directed against human-NGFr. To ensure the localization of NGFr immunoreactivity (IR) alternative sections to that processed for NGFr detection were assayed for neurofilament protein (NFP) and S-100 protein which selectively label the axon and the periaxonic specialized cells (lamellar cells of Meissner's corpuscles; inner-core cells of Pacinian corpuscles), respectively. Occurrence of NGFr IR was observed in both types of sensory corpuscles. In Meissner's corpuscles NGFr-IR was found in the lamellar cells, whereas in the Pacinian corpuscles the lamellae of the inner core, outer core, and capsule displayed NGFr IR. Moreover, a positive IR was observed in the central axon of some Pacinian corpuscles. However, remarkable differences were encountered among Pacinian corpuscles in the pattern of NGFr IR distribution. Present results demonstrate puscles in the pattern of NGFr IR distribution. Present results demonstrate the presence of NGFr IR in sensory nerve corpuscles of the human digital skin, suggesting that NGFr could be involved in the concentration of NGF and in the conveying of this molecule from the cutaneous sources to the cell body of NGF-dependent primary sensory neurons. However, the mechanisms involved in this process remain to be clarified. © 1993 Wiley-Liss, Inc.     

Pacinian Corpuscles in Human Lymph Nodes

The occurrence of Pacinian corpuscles associated to lymph nodes is an anatomical rarity and very scarce information exists in this regard. Here we examined immunohistochemically four Pacinian corpuscles found in the close vicinity of the hiliar blood vessels of lymph nodes (2 cervical, 1 axillary, and 1 inguinal) during routine surgical pathology. Pacinian corpuscles were normally arranged and displayed a pattern of protein distribution as follows: the axon was positive for neurofilament proteins and neuron specific enolase, the inner core cells showed intense S100 protein and vimentin immunostaining while they were negative for glial fibrillary acidic protein, type IV collagen and glucose transporter 1; vimentin, type IV collagen, and glucose transporter 1 were also observed also in the outer‐core and the capsule. These results are in agreement with those reported for cutaneous Pacinian corpuscles, demonstrating that the immunohistochemical profile of these corpuscles is independent of its anatomical localization. The possible functional significance of Pacinian corpuscles in lymph nodes is discussed. Anat Rec, 300:2233–2238, 2017. © 2017 Wiley Periodicals, Inc.     

Immunohistochemical demonstration of neuron specific enolase (NSE) on cutaneous nerves: comparative study using NSE and S-100 protein antibodies on denervated skin

The presence of neuron-specific enolase (NSE) and S-100 protein, which are nerve specific proteins, was immunohistochemically investigated on the cutaneous nerves. NSE was found in the axons of the cutaneous nerve bundles and the terminal axons in the Meissner and Pacinian corpuscles of the normal human and macaque skin. S-100 protein was found in the Schwann cells, lamellar cells of the Meissner corpuscles, and inner core cells of the Pacinian corpuscles. After denervation of the ulnar nerve on macaque, NSE on axons of the cutaneous nerves and Meissner and Pacinian corpuscles was completely disappeared in the 5th digit. However, S-100 protein was still maintained in the Schwann cells and Meissner and Pacinian corpuscles in the same digit. From these results, we conclude that the comparative immunohistochemical staining of NSE and S-100 protein is simple and reliable method to demonstrate the cutaneous nerves in normal and pathological conditions.     

Endocannabinoid signaling regulates regenerative axon navigation in Caenorhabditis elegans via the GPCRs NPR‐19 and NPR‐32

The axon regeneration ability of neurons depends on the interplay of factors that promote and inhibit regeneration. In Caenorhabditis elegans, axon regeneration is promoted by the JNK MAP kinase (MAPK) pathway. Previously, we found that the endocannabinoid anandamide (AEA) inhibits the axon regeneration response of motor neurons after laser axotomy by suppressing the JNK signaling pathway. Here, we show that the G‐protein‐coupled receptors (GPCRs) NPR‐19 and NPR‐32 inhibit axon regeneration in response to AEA. Furthermore, we show that sensory neuron expression of the nape‐1 gene, which encodes an enzyme synthesizing AEA, causes the regenerating motor axons to avoid sensory neurons and this avoidant response depends on NPR‐19 and NPR‐32. These results indicate that the navigation of regenerating axons is modulated by the action of AEA on NPR‐19/32 GPCRs.     

Development of Meissner‐like and Pacinian sensory corpuscles in the mouse demonstrated with specific markers for corpuscular constituents

The development of Meissner‐like and Pacinian corpuscles was studied in mice [from postnatal day (Pd) 0 to 42] by using immunohistochemistry for specific corpuscular constituents. The battery of antigens investigated included PGP 9.5 protein and neurofilaments, as markers for the central axon; S100 protein, vimentin, and p75^LNGFR protein, to show Schwann‐related cells; and epithelial membrane antigen to identify perineurial‐related cells. In Meissner‐like corpuscles immunoreactivity (IR) for neuronal markers was found by Pd7 and later. The lamellar cells of these corpuscles expressed first S100 protein IR (Pd7 to Pd42), then vimentin IR (Pd12 to Pd42), and transitory p75^LNGFR IR (Pd7 to Pd19–20). Vimentin IR, but not epithelial membrane antigen, was detected in the capsule‐like cells of the Meissner‐like corpuscles. On the other hand, the density of Meissner‐like corpuscles progressively increased from Pd0 to Pd19–20. Pacinian corpuscles were identified by Pd7. From this time to Pd42 the central axon showed IR for neuronal markers, and the inner core cells were immunoreactive for S100 protein. Moreover, vimentin IR was detected in the inner core cells by Pd19 and later. Unexpectedly, the central axons displayed S100 protein IR (from Pd7 to P28), while p75^LNGFR protein IR or epithelial membrane antigen IR were never detected. Taken together, and based on the expression of the assessed antigens alone, the present results suggest that the Meissner‐like and the Pacinian corpuscles in mice become mature around Pd19–Pd28 and Pd20, respectively. Furthermore, these results provide a baseline timetable for future studies in the normal or altered development of sensory corpuscles in mice since specific sensory corpuscles are functionally associated with different subtypes of sensory neurons the development of which is selectively disturbed in genetically manipulated mice. Anat Rec 258:235–242, 2000. © 2000 Wiley‐Liss, Inc.     

The expression of ENaC and ASIC2 proteins in Pacinian corpuscles is differently regulated by TrkB and its ligands BDNF and NT-4

Pacinian corpuscles are innervated by large myelinated Aα-β axons from the large- and intermediate-sized sensory neurons of dorsal root ganglia. These neurons express different members of the degenerin/epithelial Na⁺ channel (DEG/ENa⁺C) superfamily of proteins with putative mechanosensory properties, whose expression is regulated by the TrkB–BDNF system. Thus, we hypothesized that BDNF and/or NT-4 signalling through activation of TrkB may regulate the expression of molecules supposed to be necessary for the mechanosensory function of Pacinian corpuscles. To test this hypothesis we analyzed the expression and distribution of ENa⁺C subunits and acid-sensing ion channel 2 (ASIC2) in Pacinian corpuscles from 25 days old mice deficient in TrkB, BDNF and NT-4. Pacinian corpuscles in these animals are normal in number, structure, and expression of several immunohistochemical markers. Using immunohistochemistry we observed that the β-ENa⁺C and γ-ENa⁺C subunits, but not the α-ENa⁺C subunit, were expressed in wild-type animals, and they were always found in the central axon. ASIC2 immunoreactivity was found in both the central axon and the inner core cells. The absence of TrkB or BDNF abolished expression of β-ENa⁺C and ASIC2, whereas expression of γ-ENa⁺C did not change. Expression of β-ENa⁺C and γ-ENa⁺C subunits in NT-4 deficient mice was found in the axons but also in the inner core cells whereas levels of expression of ASIC2 were increased in these animals. This study suggests that expression in Pacianian corpuscles of some potential mechanosensory proteins is regulated by BDNF, NT-4 and TrkB.     

Vibration-evoked responses from lamellated corpuscles in the legs of kangaroos

Summary A group of lamellated corpuscles are present in the interosseous region of the legs of macropod marsupials. Structurally, they are similar to, but simpler than the Pacinian corpuscles of eutherian mammals, in having fewer lamellae. Responses of mechanoreceptors with axons coursing in the interosseous nerve were recorded from filaments, containing single functional units, dissected from the sciatic nerve of the wallaby Thylogale billardierii. The receptors were all maximally sensitive to stimuli applied in the interosseous region, where the cluster of lamellated corpuscles is located. Most units had low mechanical thresholds and were sensitive to sinusoidal vibration over a wide range of frequencies. Functional properties generally resembled those of eutherian Pacinian corpuscles, but the marsupial receptors were less rapidly adapting. The afferent nerve fibres conducted at 45 to 60 ms^–1, while the diameter of axons in the osmium-stained interosseous nerve ranged between 7.5 and 12 m. It is suggested that one important function of the receptors might be the detection of ground-borne vibration.     

Vesicular acetylcholine transporter can be a morphological marker for the reinnervation to muscle of regenerating motor axons

This study was designed to evaluate whether the vesicular acetylcholine transporter (VAChT), which packages acetylcholine into synaptic vesicles, can be used as a marker for regenerating motor axon terminal. We examined motor axon regeneration in the tongue after hypoglossal nerve axotomy, using an anterograde tracer biotin-dextran (BD), retrograde tracer Fluoro-Gold (FG), electron microscopic (EM) observation, and VAChT immunocytochemistry. BD study demonstrated that outgrowth of thin regenerating axons into the frontal area of the tongue was firstly observed at 14 post-operative days, and presynaptic formation of neuromuscular junction (NMJ) was observed from 21 post-operative days. Under electron microscopic observation, reconstruction of new NMJs was observed within the interval between 21 and 28 days. VAChT-immunoreactive nerve terminals disappeared by 3 days after axotomy, slightly appeared at 14 post-operative days, and thereafter gradually increased in number from 21 to 28 post-operative days. The re-expression of VAChT positive presynaptic terminal was almost the same as those obtained in BD, FG and EM studies. Regenerating axons tip in the crush model of the hypoglossal nerve exhibited prominent VAChT immunoreactivity in growing tip of regenerating axons. These indicate that VAChT is an excellent morphological indicator for regenerating nerve terminals of motor neurons.     

Axonal regeneration of cat retinal ganglion cells is promoted by nipradilol, an anti-glaucoma drug

Neurons in the CNS can regenerate their axons in an environment of the peripheral nervous system, but this ability is limited. Here we show that an anti-glaucoma drug, nipradilol, at low concentration led to a four-fold increase in the number of cat retinal ganglion cells regenerating their axons into a transplanted peripheral nerve 4 and 6 weeks after axotomy. Nipradilol also increased the number of three main regenerating retinal ganglion cell types (alpha, beta, not alpha/beta), and enhanced the rate of axonal regeneration of these retinal ganglion cells. Nipradilol is a donor of nitric oxide and an antagonist of alpha-1, beta-1 and -2 adrenoreceptors, and we therefore examined whether one of these pharmacological effects might be more important in promoting axon regeneration. A nitric oxide donor increased the number of regenerating retinal ganglion cells, but not the rate of axonal regeneration. Denitro-nipradilol (nitric oxide-deprived nipradilol) or a nitric oxide scavenger injected before nipradilol increased the number of regenerating retinal ganglion cells but did not promote regeneration rate. Blockade of individual alpha- and beta-adrenoreceptors did not increase the number of regenerating retinal ganglion cells or the rate of regeneration. From these results, it is suggested that nitric oxide plays a crucial role in mediating the effects of nipradilol on axon regeneration and neuroprotection, and the metabolite of nipradilol supports the effects.