Localization of substance P-immunoreactive nerve fibers in the human digital skin

Substance P-immunoreactive nerve endings were localized in human digital skin by the use of indirect immunohistochemical technique. It was found that substance P-like immunoreactivity was present in free nerve endings in the dermal papillae and in the epidermis. Some Meissner's corpuscles also contained substance P positive nerve endings. Furthermore, substance P-immunoreactive nerves were localized in close connection to sweat gland ducts and blood vessels. The functional significance of these findings was discussed with regard to pain mediation and inflammatory response.     

Localization of substance P-like immunoreactivity in Hydra.

Substance P-like immunoreactivity was found in Hydra attenuata mainly but not exclusively in the nerve and interstitial cells, localized in the cytoplasm and on the cell surface membranes.     

L1CAM malfunction in the nervous system and human carcinomas

Research over the last 25 years on the cell adhesion molecule L1 has revealed its pivotal role in nervous system function. Mutations of the human L1CAM gene have been shown to cause neurodevelopmental disorders such as X-linked hydrocephalus, spastic paraplegia and mental retardation. Impaired L1 function has been also implicated in the aetiology of fetal alcohol spectrum disorders, defective enteric nervous system development and malformations of the renal system. Importantly, aberrant expression of L1 has emerged as a critical factor in the development of human carcinomas, where it enhances cell proliferation, motility and chemoresistance. This discovery promoted collaborative work between tumour biologists and neurobiologists, which has led to a substantial expansion of the basic knowledge about L1 function and regulation. Here we provide an overview of the pathological conditions caused by L1 malfunction. We further discuss how the available data on gene regulation, molecular interactions and posttranslational processing of L1 may contribute to a better understanding of associated neurological and cancerous diseases.     

Kinesins in the nervous system

Both the development and the maintenance of neurons require a great deal of active cytoplasmic transport. Much of this transport is driven by microtubule motor proteins. Membranous organelles and other macromolecular assemblies bind motor proteins that then use cycles of adenosine 5'-triphosphate hydrolysis to move these 'cargoes' along microtubules. Different sets of cargoes are transported to distinct locations in the cell. The resulting differential distribution of materials almost certainly plays an important part in generating polarized neuronal morphologies and in maintaining their vectorial signalling activities. A number of different microtubule motor proteins function in neurons; presumably they are specialized for accomplishing different transport tasks. Questions about specific motor functions and the functional relationships between different motors present a great challenge. The answers will provide a much deeper understanding of fundamental transport mechanisms, as well as how these mechanisms are used to generate and sustain cellular asymmetries.     

Histone deacetylases: Focus on the nervous system

Neurodegenerative disease strikes millions worldwide and there is mounting evidence suggesting that underlying the onset and progression of these debilitating diseases is inappropriate neuronal apoptosis. Recent reports have implicated a family of proteins known as histone deacetylases (HDACs) in various neuronal processes including the neuronal death program. Initial headway in this field has been made largely through the use of broad-spectrum HDAC inhibitors. In fact, pharmacological inhibition of HDAC activity has been shown to protect neurons in several models of neurodegeneration. The observation that HDAC inhibitors can have opposing effects in different paradigms of neurodegeneration suggests that individual members of the HDAC protein family may play distinct roles that could depend on the specific cell type under study. The purpose of this review is to detail work involving the use of HDAC inhibitors within the context of neurodegeneration and examine the roles of individual HDAC members in the nervous system with specific focus on neuronal cell death. Received 25 January 2007; received after revision 3 April 2007; accepted 26 April 2007     

Localization of biogenic amines in the central nervous system of Crepidula fornicata (Phil.), Mollusca, Gastropoda, Prosobrancha]

Two categories of neurones at least can be demonstrated in Crepidula fornicata, some containing catecholamines (DA) others indolamines (5 HT). These cells, which are well localized, are often close to azanophilous neurosecretory cells but nevertheless distinct from the latter.     

Targeting NOX enzymes in the central nervous system: therapeutic opportunities

Among the pathogenic mechanisms underlying central nervous system (CNS) diseases, oxidative stress is almost invariably described. For this reason, numerous attempts have been made to decrease reactive oxygen species (ROS) with the administration of antioxidants as potential therapies for CNS disorders. However, such treatments have always failed in clinical trials. Targeting specific sources of reactive oxygen species in the CNS (e.g. NOX enzymes) represents an alternative promising option. Indeed, NOX enzymes are major generators of ROS, which regulate progression of CNS disorders as diverse as amyotrophic lateral sclerosis, schizophrenia, Alzheimer disease, Parkinson disease, and stroke. On the other hand, in autoimmune demyelinating diseases, ROS generated by NOX enzymes are protective, presumably by dampening the specific immune response. In this review, we discuss the possibility of developing therapeutics targeting NADPH oxidase (NOX) enzymes for the treatment of different CNS pathologies. Specific compounds able to modulate the activation of NOX enzymes, and the consequent production of ROS, could fill the need for disease-modifying drugs for many incurable CNS pathologies.     

Dense core vesicles in cerebral cortex of the human fetus.

The present study clearly demonstrates that by the 15th week of gestation dense core vesicles appear within the human cerebral cortex. These vesicles can be identified within axon cylinders, axon growth cones, and axon synaptic terminals. The role of these vesicles is speculative, yet, their very presence at this early fetal stage seems to reflect an advanced state of synaptic vesicle development.     

The stability of purified preparations of substance P

Zusammenfassung Hochgereinigte Präparate von Substanz P sind in verdünnter Lösung nicht stabil, da die aktive Substanz an Glas adsorbiert wird. Der Verlust an Wirksamkeit konnte durch Zusatz von Protein zur Lösung weitgehend verhindert werden. Die wirksame Substanz kontrahierte den Darm von Meerschweinchen, Huhn und Goldfisch, war aber am Rattenuterus fast wirkungslos.     

Antidiuretic activities of substance P and its analogs

Summary Substance P (SP) and analogs, including 5 nucleoside (ARA or HRA)-peptides, were examined for antidiuretic activity in ethanolized rats. The activity was potent in the analogs embodying the C-terminal hexapeptide, weak in the nucleoside-pentapeptide, and negligible in the nucleoside-tetrapeptide. In addition, the activity was increased by acylation of the hexapeptide. The antidiuretic potencies were also compared with the hypotensive potencies.This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Japan, and by a grant from the Imanaga Foundation, Nagoya, Japan.     

The neurogenic activity of high potency substance P

Zusammenfassung Gereinigte Präparate von Substanz P mit Aktivitäten von 10, 1000 und 10 000 E/mg verstärken das vierte Potential der dorsalen Nervenwurzel im Rückenmark der Katze (Verabreichung nach LSD). Unsere Befunde bestätigen frühere Beobachtungen und legen die Vermutung nahe, dass bei fortschreitender Reinigung ein Teil der neurotropen Aktivität zusammen mit der leiotropen angereichert wird.     

Heat shock response in the central nervous system

The heat shock response is induced in nervous tissue in a variety of clinically significant experimental models including ischemic brain injury (stroke), trauma, thermal stress and status epilepticus. Excessive excitatory neurotransmission or the inability to metabolically support normal levels of excitatory neurotransmission may contribute to neuronal death in the nervous system in many of the same pathophysiologic circumstances. We demonstrated that in vitro glutamate-neurotransmitter induced excitotoxicity is attenuated by the prior induction of the heat shock response. A short thermal stress induced a pattern of protein synthesis characteristic of the highly conserved heat shock response and increased the expression of heat shock protein (HSP) mRNA. Protein synthesis was necessary for the neuroprotective effect. The study of the mechanisms of heat shock mediated protection may lead to important clues as to the basic mechanisms underlying the molecular actions of the HSP and the factors important for excitotoxic neuronal injury. The clinical relevance of these findings in vitro is suggested by experiments performed by others in vivo demonstrating that pretreatment of animals with a submaximal thermal or ischemis stress confers protection from a subsequent ischemic insult.     

Multitasking with neurotensin in the central nervous system

The 13-amino acid peptide neurotensin (NT) was discovered over 30 years ago and has been implicated in a wide variety of neurotransmitter and endocrine functions. This review focuses on four areas where there has been substantial recent progress in understanding NT signaling and several functions of the endogenous peptide. The first area concerns the functional activation of the high-affinity NT receptor, NTR-1, including the delineation of the NT binding pocket and receptor domains involved in functional coupling to intracellular signaling pathways. The development of NT receptor antagonists and the application of genetic and molecular genetic approaches have accelerated progress in understanding NT function in several areas, including the involvement of NT in antipsychotic drug actions, psychostimulant sensitization and the modulation of pain, and these are reviewed in that order. There is now substantial evidence indicating that NT is required for certain antipsychotic drug actions and that the peptide plays a key role in stress-induced analgesia.Received 18 March 2005; received after revision 9 May 2005; accepted 23 May 2005     

Collagens in the developing and diseased nervous system

Collagens are extracellular proteins characterized by a structure in triple helices. There are 28 collagen types which differ in size, structure and function. Their architectural and functional roles in connective tissues have been widely assessed. In the nervous system, collagens are rare in the vicinity of the neuronal soma, occupying mostly a “marginal” position, such as the meninges, the basement membranes and the sensory end organs. In neural development, however, where various ECM molecules are known to be determinant, recent studies indicate that collagens are no exception, participating in axonal guidance, synaptogenesis and Schwann cell differentiation. Insights on collagens function in the brain have also been derived from neural pathophysiological conditions. This review summarizes the significant advances which underscore the function and importance of collagens in the nervous system. Received 09 September 2008; received after revision 24 October 2008; accepted 28 October 2008     

The effect of substance P on the amount of 5-Hydroxytryptamine in the gut

Résumé L'injection intrapéritonéale de la substanceP (60 à 120 U/kg) chez le rat provoque une augmentation marquée de 5-HT dans la paroi de l'estomac et dans l'iléon. Dans la rate de cet animal, on n'y observe pas d'augmentation de 5-HT.L'administration intraluminale de la substanceP (60–80 U) dans l'iléon isolé du cobaye, augmente aussi sensiblement la quantité de 5-HT.     

Neurexins and neuroligins: synapses look out of the nervous system

The scientific interest in the family of the so-called nervous vascular parallels has been growing steadily for the past 15 years, either by addition of new members to the group or, lately, by deepening the analysis of established concepts and mediators. Proteins governing both neurons and vascular cells are known to be involved in events such as cell fate determination and migration/guidance but not in the last and apparently most complex step of nervous system development, the formation and maturation of synapses. Hence, the recent addition to this family of the specific synaptic proteins, Neurexin and Neuroligin, is a double innovation. The two proteins, which were thought to be “simple” adhesive links between the pre- and post-synaptic sides of chemical synapses, are in fact extremely complex and modulate the most subtle synaptic activities. We will discuss the relevant data and the intriguing challenge of transferring synaptic activities to vascular functions.