Role Of Nerves Research Articles

Establishment of mouse cell lines expressing Mycobacterium leprae 65 KDa heat shock protein gene.

Neurotropism is one of the most important characteristics of Mycobacterium leprae (M. leprae). It is believed that nerve damage of leprosy is caused by various immune mechanisms 1), and so called "autoimmune reaction" is suspected to have one of the role in nerve damage.M. leprae 65 kDa heat-shock protein (hsp65) has noticeable characteristics. Hsp65 is a highly conserved protein2). Itbelongs to the family of groEL proteins3). The amino acid sequence of M. leprae hsp65 shows homology of more than 90% with other mycobacterial hsp65s and shares around 48% amino acid identity with the mammalian mitochondrial P1 or hsp 604). Hsp65 was also reported to be a highly immunogenic protein of M. leprae in both Bcell and T-cell responses5, 6). Recently, many reports have described the relationships between hsp65 and some autoimmune diseases such as Kawasaki disease7), rheumatoid arthritisa8) and so on; the role of hsp65 in immunological disorders may be one of molecular mimicry9). Freedman et al described the expression of hsp 60 and hsp 70 by human glial cells. Such hsps were supposed to be the recognition molecule (s) for γ δT cells which mediated glial cell lysis in uitro 10 There are no providing mechanisms for nerve damage in leprosy just now, but the molecule(s) of hsp65 may at least be the possible candidate as a recognition molecule for γ δT cells generated during M. leprae infection.In this paper we reported stablishment of mouse cell lines showing stable expression of M. leprae hsp65, such cell lines would work as a target cell in cytolysis assay in vitro for cytotoxic T cells and γ δT cells generating during M, leprae infections.

Pain in Chronic Pancreatitis: The Role of Nerves

The perception of pain depends upon signals carried by nerves to appropriate locations in the central nervous system. It is well known that when stretch receptors in the gastrointestinal tract are sti

Effect of neural blockades, gastrointestinal regulatory peptides, and diversion of gastroduodenal contents on periodic pancreatic secretion in the preruminant calf.

The role of nerves, gastrointestinal peptides, and gastroduodenal contents in the regulation of pancreatic periodic function were studied in preruminant calves. Nine male, Friesian calves were surgically fitted with pancreatic and duodenal catheters, abomasal and duodenal cannulae, and duodenal electrodes. Pancreatic secretion oscillated in phase with the duodenal migrating myoelectric complex. Pancreatic secretion and duodenal motility were abolished by intravenous atropine (5 micrograms.kg-1.min-1). The frequency of pancreatic and duodenal cycles was similarly increased by motilin and decreased by pituitary adenylate cyclase activating polypeptide-27; secretin lengthened duodenal but not pancreatic cycles, resulting in loss of synchronization; cholecystokinin-8 and secretin increased pancreatic secretion (all infusions at 120 pmol.kg-1.h-1); intraduodenal lidocaine (2%) or diversion of gastroduodenal contents reduced pancreatic secretion without altering periodicity. In conclusion, generation of pancreatic as well as of duodenal periodicity in the calf depends upon cholinergic neural efferent input. Secretin, cholecystokinin-8, pituitary adenylate cyclase activating polypeptide, duodenal contents, and mucosal afferent receptors seem to have relatively minor regulatory roles but can modulate the level of pancreatic secretion. The importance of enteric neural influence from the duodenum and the role of motilin in the regulation of pancreatic periodicity and its synchronization with the duodenal motility cycle remain to be determined.

Regulation of Dihydropyridine and Ryanodine Receptor Gene Expression in Skeletal Muscle: ROLE OF NERVE, PROTEIN KINASE C, AND cAMP PATHWAYS

The dihydropyridine (DHP) and ryanodine (RY) receptors play a critical role in depolarization-induced calcium release in skeletal muscle, yet the factors which govern their expression remain unknown. We investigated the roles of electrical activity and trophic factors in the regulation of the genes encoding the alpha 1, alpha 2, and beta subunits of the DHP receptor as well as the RY receptor in rat skeletal muscle in vivo. Muscle paralysis, induced by denervation, had no effect on the DHP receptor mRNA levels while the RY receptor mRNA was decreased. In contrast, chronic superfusion of tetrodotoxin onto the sciatic nerve resulted in a marked increase in mRNA levels and transcriptional activity of both DHP and RY receptor genes. Since nerve can induce changes in second messenger pathways which modulate muscle gene expression, we attempted to identify factors which regulate DHP and RY receptor expression using cultured myotubes. Elevated cAMP levels specifically inhibited the expression of RY receptor mRNA while 12-O-tetradecanoylphorbol-13-acetate, an activator of protein kinase C, increased the transcripts encoding the RY receptor and the alpha 1 subunit of the DHP receptor. Changes in the level of mRNAs were paralleled by altered receptor numbers. Neither cAMP nor protein kinase C altered transcriptional activity of the DHP and RY receptor genes. These results demonstrate that neural factor(s) regulate DHP and RY receptor mRNA levels in vivo via transcriptional mechanisms while protein kinase C and cAMP can modulate DHP and RY receptor transcript levels by a transcription-independent process.

The early distribution and possible role of nerves during odontogenesis.

Neural crest cells migrate along specific pathways to reach the mandibular and maxillary arches where they condense under specific areas of the ectoderm which will give rise to the primary and permanent dentition. In the mouse, the trigeminal ganglion becomes evident on E9 and the superior cervical sympathetic ganglion E13. Several studies have suggested that nerves in the vicinity of the developing teeth could influence the surrounding tissues and initiate tooth development, whereas other investigators have suggested that tooth development will proceed without an intact innervation. Innervation of the dental papilla has been reported as early as the cap stage in human teeth using an antibody to PGP 9.5. A large variety of putative neurotransmitters have been localized in the nerves of the dental pulp. Many of the putative neurotransmitters function in vasoregulation while others have unknown functions. A hypothesis is presented describing a possible signal transduction pathway between odontoblasts and nerve terminals.

The role of nerves, hormones and nutrients in the control of food intake

The role of nerves, hormones and nutrients in the control of food intake

Aetiological aspects of mandibular tooth agenesis--focusing on the role of nerve, oral mucosa, and supporting tissues.

The purpose of the present investigation was to consider possible aetiological aspects of mandibular tooth agenesis by comparing the pattern of mandibular molar and premolar agenesis with radiological evidence of the mandibular canal. Orthopantomograms from 33 children affected by agenesis of at least four premolar and/or molar teeth in the mandible were investigated. Three children were affected by ectodermal dysplasia. Two anthropological mandibles with absence of mandibular canals were included in the study for comparison. According to the investigation, agenesis should be divided into three groups, based on an analysis of agenesis location, the presence of nerve canals in the jaws, and finally, data on possible bone, skin and oral mucosa abnormalities. The three aetiological groups suggested are: agenesis related to nerve tissue, agenesis related to the oral epithelium, and agenesis related to the supporting tissue.

The effect of denervation on myosin isoform synthesis in rabbit slow-type and fast-type muscles during terminal differentiation. Denervation induces differentiation into slow-type muscles.

The soleus and gastrocnemius medialis of eight-day-old rabbits were denervated and the effects were examined after fifty-two days by biochemical, cytochemical and mechanical methods. The contralateral soleus exhibited the properties of slow-type muscle, namely a predominance of slow-type myosin isoforms and slow-type oxidative fibers, slow twitch and low maximal velocity for shortening. The contralateral gastrocnemius exhibited the properties of fast-type muscle, namely a predominance of fast-type myosin isoforms and fast-type non-oxidative fibers, fast twitch and high maximal velocity of shortening. Denervation of muscles caused the differentiation of the two muscles towards slow-type muscles. Both denervated soleus and gastrocnemius muscles exhibited a predominance of slow-type myosins (either the normal type, made up of slow heavy and light chains, or the hybrid type, made up of slow heavy and regulatory light chains and fast essential light chains), a predominance of slow-type fibers, and slow mechanical properties. Thus, innervation in rabbit appears to be a determining factor for differentiation into fast-type muscle, but it is not necessary for differentiation into slow-type muscle. This conclusion contradicts the findings of previous studies in rat and thus raises new questions concerning the role of nerves in controlling the expression of myosin isoforms and the differentiation of muscle fibers.

Chronic Pancreatitis: Morphology and the Role of Nerves

Chronic pancreatitis is a regressive disease, sometimes progressing to the point of insufficient secretion from both the exocrine and the endocrine pancreas. Functional decline is matched by morphological changes in the parenchyma and stroma. Acinar cells redifferentiate to produce tubular complexes and degenerate, resulting in a larger proportion of ductular cells than normal. The decrease in parenchyma is more than made up for by an increase in stroma. Characteristically, marked fibrosis occurs. Chronic inflammatory cells are prominent, frequently occurring as clusters. The large pancreatic ducts are altered as well. They may be denuded of their epithelium, eliminating the barrier that normally exists. Plasma cells and inflammatory cells in their walls contribute to the extra components that are found in pancreatic juice. Pancreatic stones, consisting of calcium carbonate precipitated in an organic matrix, may form in the ducts. Chronic inflammatory cells cluster around nerves in and around the pancreas, inducing damage to the perineurium and eventually affecting nerve fibers. This direct damage, coupled with abnormal access of foreign substances to the interior of the nerves due to lack of the perineurial barrier, may provide a partial explanation for the chronic pain that is associated with the disease.

A Study of General Innervation of the Human Adrenal Cortex Using PGP 9.5 Immunohistochemistry

Immunohistochemical detection of the neurone-specific ubiquitin hydrolase protein gene product 9.5 (PGP 9.5) has been applied to the normal adult human adrenal cortex to define overall patterns of innervation. Three distinct types of nerve morphology were noted in the cortex: large nerve trunks traversing the cortex to the medulla, a complex, branching network of slender nerve bundles and individual nerve fibres. These were more abundant in the head and body than in the alae and tail. Varicosities suggested local neurotransmitter release. Nerve fibres were also identified in the muscular wall of the central vein, which are apparently neither noradrenergic nor cholinergic. These data are in support of a direct role for nerves in the control of adrenocortical function and/or vascular responses in man.

The role of nerves in gastrointestinal physiology

The role of nerves in gastrointestinal physiology

Role of nerves in hypertension

Role of nerves in hypertension

Role of nerve and tension in maturation of posthatching slow-tonic muscle in chicken.

The role of motor innervation and muscle tension in the posthatching maturation of the slow-tonic anterior latissimus dorsi (ALD) muscle of the chicken has been investigated. Modification of the muscle tension was obtained either by maintaining ALD in a shortened state or by stretching, after or without denervation. In denervated as well as in innervated ALD, shortening resulted in atrophy and inhibition of developmental change in muscle fiber population. In contrast, stretch causes hypertrophy, transformation of all 3B fibers, increase in SM2 isomyosin expression, and decrease in Ca2+-activated myosin ATPase in innervated or denervated ALD. On the other hand oxidative activity in ALD fibers was strikingly reduced after denervation even in presence of stretch-induced hypertrophy. This study suggests that a passive stretch can be involved in some, but not all, changes in ALD characteristics occurring after denervation and may be also involved in normal posthatching development of the slow-tonic muscle. Possible clinical implications of these results in relation to treatments for preventing muscle atrophy resulting from immobilization or disuse are suggested.

Role of nerve and muscle factors in the development of rat muscle spindles

The soleus muscles of fetal rats were examined by electron microscopy to determine whether the early differentiation of muscle spindles is dependent upon sensory innervation, motor innervation, or both. Simple unencapsulated afferent-muscle contacts were observed on the primary myotubes at 17 and 18 days of gestation. Spindles, encapsulations of muscle fibers innervated by afferents, could be recognized early on day 18 of gestation. The full complement of spindles in the soleus muscle was present at day 19, in the region of the neuromuscular hilum. More afferents innervated spindles at days 18 and 19 of gestation than at subsequent developmental stages, or in adult rats; hence, competition for available myotubes may exist among afferents early in development. Some of the myotubes that gave rise to the first intrafusal (bag2) fiber had been innervated by skeletomotor (alpha) axons prior to their incorporation into spindles. However, encapsulated intrafusal fibers received no motor innervation until fusimotor (gamma) axons innervated spindles 3 days after the arrival of afferents and formation of spindles, at day 20. The second (bag1) intrafusal fiber was already formed when gamma axons arrived. Thus, the assembly of bag1 and bag2 intrafusal fibers occurs in the presence of sensory but not gamma motor innervation. However, transient innervation of future bag2 fibers by alpha axons suggests that both sensory and alpha motor neurons may influence the initial stages of bag2 fiber assembly. The confinement of nascent spindles to a localized region of the developing muscle and the limited number of spindles in developing muscles in spite of an abundance of afferents raise the possibility that afferents interact with a special population of undifferentiated myotubes to form intrafusal fibers.

Cell cycle controls and the role of nerves and the regenerate epithelium in urodele forelimb regeneration: possible modifications of basic concepts.

Data from pulse and continuous labeling with [3H]thymidine and from studies with monoclonal antibody WE3 have led to the modification of existing models and established concepts pertinent to understanding limb regeneration. Not all cells of the adult newt blastema are randomly distributed and actively progressing through the cell cycle. Instead, many cells are in a position that we have designated transient quiescence (TQ) and are not actively cycling. We postulate that cells regularly leave the TQ population and enter the actively cycling population and vice versa. The size of the TQ population may be at least partly determined by the quantity of limb innervation. Larval Ambystoma may have only a small or nonexisting TQ, thus accounting for their rapid rate of regeneration. Examination of reactivity of monoclonal antibody WE3 suggests that the early wound epithelium, which is derived from skin epidermis, is later replaced by cells from skin glands concomitant with blastema formation. WE3 provides a useful tool to further investigate the regenerate epithelium.

Immunohistochemical study on the distribution of neuron‐specific enolase‐ and peptide‐containing nerves in the omasum of cattle

The distribution of nerves containing immunoreactivity for substance P (SP), vasoactive intestinal polypeptide (VIP), leucine-enkephalin (LENK), and gastrin-releasing polypeptide (GRP) in the margin of the reticulo-omasal orifice, omasum, and omasal pillar of calves and cows was studied by immunohistochemistry. The general distribution of nerves was determined by means of neuron-specific enolase (NSE) antiserum and then compared to the distribution of immunoreactive (IR) nerves stained for the four peptides. Marked differences in the distribution of immunoreactive nerves were associated with age and the segment examined. SP-IR fibers were abundant in the musculature of the ungulate papillae at the reticulo-omasal orifice and in the smooth muscle of the omasal leaves, moderately dense in the omasal pillar, and low in density in the inner muscle layer of the reticulo-omasal orifice and in the muscle of the omasal wall. In order of decreasing abundance, the cell bodies of SP-IR nerves were found at the reticulo-omasal orifice, in the omasal wall, and in the omasal pillar. LENK-IR fibers, though less abundant, showed a pattern of distribution that was similar to that of SP-IR fibers. Nerve cell bodies showing weak immunoreactivity for LENK were detected rarely. Abundant VIP-IR fibers were present in the inner muscle layer of the reticulo-omasal orifice and in the omasal wall, while moderate numbers were seen in the omasal pillar: they were low in density in the ungulate papillae and omasal leaves. Cell bodies of VIP-IR nerves decreased in number through the omasum, reticulo-omasal orifice, and omasal pillar. The distribution of GRP-IR nerve fibers was similar to that of VIP-IR fibers, although GRP-IR fibers were less abundant. Nerve cell bodies showing weak immunoreactivity for GRP were detected rarely. The individual distribution of peptide-IR nerves was similar in the calf and cow, but immunoreactive nerves were far more abundant in the calf. The present study provides valuable information for discussion of the possible role of nerves in the regulation of omasal function.

Lymph heart musculature in birds.

Development and innervation of the lymph heart musculature of chicken, emu, rhea, and duck was studied by electron microscopy at post-hatch ages from 3 days to adulthood. Development of innervation was monitored by acetylcholinesterase staining. Horseradish peroxidase was used to determine the extent of the transverse tubule network. Chickens were unusual among these birds in that lymph heart myocytes had already undergone a definitive differentiation and degeneration by 3 days. In ducks and ratite birds, lymph heart myocytes more slowly but progressively differentiate a cytomorphology that does not conform in all characteristics to cardiac or skeletal muscle and even resembles in some aspects, smooth muscle. Myofibrils become the dominant cytoplasmic structure, transverse tubules form "internal couplings" with agranular reticulum cisternae, and "external couplings" are formed between myocytes at myomyal junctions. The myomyal junctions also contain AChE-positive reaction product and some subplasmalemmal vesicles that lack a dense core. The lymph heart myocardium of ducks of 2 weeks demonstrated mitotic figures. In adult ducks the myosatellite cell numbers diminish and a characteristic pattern of myocyte degeneration appears. In juvenile ducks and ratites some myocytes differentiate to conductile cells, much as the conductile myocytes and myofibers of the blood heart. The lymph heart innervation is described, and the role of nerve in differentiation and maintenance of myocyte morphology in the lymph heart is discussed.

Rat renal hemodynamics during venous compression: roles of nerves and prostaglandins.

Experiments were conducted on euvolemic rats to characterize renal hemodynamic responses to a unilateral increase in renal venous pressure. Ipsilateral renal blood flow (RBF, electromagnetic flow probe) was measured in four groups to determine the roles of the renal nerves and endogenous prostaglandins. In control rats, elevation of venous pressure (3 to 22 mmHg) produced vasoconstriction and a 16% increase in renal vascular resistance (RVR) at 130 mmHg arterial pressure (P less than 0.001). In acutely denervated kidneys, a 19-mmHg increase in venous pressure reduced RBF but did not alter RVR (5% decrease), since there were proportional decreases in RBF and the arteriovenous pressure gradient. Indomethacin-treated rats with innervated kidneys responded to a similar increase in venous pressure with pronounced constriction; RVR increased by 50% (P less than 0.005). Venous compression elicited a 24% increase in RVR (P less than 0.05) in indomethacin-treated rats with denervated kidneys. The opposing effects of denervation and indomethacin treatment were significant and noninteractive. The findings indicate 1) activation of an ipsilateral renorenal neural reflex mediated a significant portion of the vasoconstriction; and 2) enhanced synthesis of prostaglandins produced net dilatory effects that attenuated the neurally mediated constriction. The opposing actions of the renal nerves and prostaglandins on the RVR responses to increased venous pressure were directly related to arterial pressure between 70 and 130 mmHg. In response to decrements in arterial pressure, the general pattern of vasodilation was not impaired by denervation of indomethacin when venous pressure was normal or elevated. These observations indicate that the origin of the pressure change, i.e., arterial vs. venous, engages different vasoactive factors that are responsible for varying circulatory responses in the rat kidney.

Neural control of periodic secretion of the pancreas and the stomach in fasting dogs.

The role of nerves in periodic secretion of the pancreas and the stomach in relation to the motility of the upper gastrointestinal tract was studied in conscious fasting dogs which had previously been provided with chronic gastric and pancreatic fistulae and a Heidenhain pouch. Both atropine and pentolinium abolished the periodic increase in gastric and pancreatic secretion and motility of the gut. Bilateral cervical vagal blockade with lidocaine reduced the motility of the stomach, the duodenum and the pouch preceding their peaks, but the motility at the peaks remained unchanged except in the case of the stomach. Pancreatic secretion preceding its peak was also decreased by vagal blockade but that at the peak was not significantly different from the control peak. Periodic pepsin secretion, from both the fistula and pouch, was decreased by vagal blockade. It is concluded that the secretion and motility of the upper gut in fasting dogs is controlled by periodic activity of the vagus and intrinsic nerves.

Neurotrophic control of events in injured forelimbs of larval urodeles

Denervated forelimbs and contralateral innervated forelimbs of Ambystoma larvae were injured internally distal to the elbow by compression with watchmaker's forceps. Innervated controls completely repaired the crush injury within one week; denervated limbs failed to repair the injury and exhibited varying degrees of limb regression. Histological examination revealed that the process of tissue dedifferentiation initiated by injury was more extensive in denervated, regressing limbs than in controls. In innervated limbs, both the DNA labeling index and the mitotic index peaked approximately 4--6 days after the injury and returned to baseline levels by 10 days. In denervated limbs, the DNA labelling index also increased and remained at an elevated level for at least 2 weeks after the injury, but significant mitotic activity was not observed. The data indicate that intact nerves are not needed for cellular dedifferentiation, cell cycle re-entry, and DNA synthesis in injured limbs, but are required for the cells to proliferate and repair the injury. These results are discussed together with those of similar experiments on the role of nerve during the initiation of epimorphic regeneration in amputated limbs.