Browsing by Author "Alvarez, J"

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    Acetylcholinesterase and inhibitors: effects upon normal and regenerating nerves of the rat
    (1999) Keymer, JE; Gaete, J; Kameid, G; Alvarez, J
    In peripheral nerves, the function of acetylcholinesterase (AChE) is not related to hydrolysis of acetylcholine. To test for a trophic role, AChE or its inhibitors were administered locally to normal and regenerating nerves of rats. In the normal nerve, neither AChE nor serum albumin affected the cytological pattern of the nerve. BW284c51, a specific inhibitor of AChE, resulted in demyelination, proliferation of Schwann cells and sprouting of axons after 5-7 days. Edrophonium or propidium, other specific inhibitors of AChE, did so to a much lesser extent. Vehicle, and iso-OMPA (inhibitor of pseudocholinesterases) did not affect the cytology of the nerve. Elongation of regenerating axons was evaluated at day 3 post-crush. Native AChE applied distal to the crush reduced the elongation of regenerating axone (-36%), while serum albumin, heated AChE and filtered AChE did not. BW284c51, edrophonium or propidium enhanced the axonal elongation (33%) when they were administered for 2 days before, but not after, the crush. Iso-OMPA or vehicle administered before or after the crush were not effective. Thus, AChE reduces elongation of regenerating axons, while inhibition of AChE enhances elongation and affects the cytology of the normal nerve as well. We propose that AChE has a trophic role in mammalian peripheral nerves.
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    Cerebrospinal fluid of HTLV-1 associated myelopathy patients induces axonal sproutings and Schwann cell proliferation in the rat sciatic nerve
    (1998) Nien, JK; Schmidt, J; Cartier, L; Alvarez, J
    HTLV-1 (human T-cell leukemia virus type I) associated myelopathy (HAM) is a demyelinating disease. We showed that the CSF of patients and heated CSF of normal subjects induce a segmentary demyelination in rat nerves, and potentiate trypsin in vitro. Here we further characterize the neuropathy induced by the CSF of patients. Peroneal nerves injected 5-8 days before with native or heated CSF of patients, besides extensive demyelination, presented proliferation of myelinating and nonmyelinating Schwann cells, axonal sprouting, fine fibres with a few turns of myelin, disarray of nonmedullated bundles, desmosome-like junctions, and coated pits and vesicles in Schwann cells and axons. The normal CSF was innocuous to the nerve in its native form, but after heating, it induced a neuropathy in all, similar to that elicited by the CSF of patients. Our findings indicate that the CSF of HAM patients contains a thermostable pathogen for nerves of the rat; a thermostable pathogen also occurs in the normal CSF although its activity is checked by endogenous thermolabile factors. We suggest that the pathogen present in the CSF of HAM patients participates in the disease. (C) 1998 Elsevier Science B.V. All rights reserved.
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    Isolated axone of Wlds mice regrow centralward
    (1999) Iñiguez, A; Alvarez, J
    We have conjectured that axons embody a post transcriptional sprouting programme repressed by mature Schwann cells. Injured nerves of Wld(s) mice neither degenerate nor regenerate for several weeks but axone do regrow if the resident cells of the distal stump are destroyed. To test our hypothesis we made an extended crush in Wld(s) nerves to destroy resident cells, transected the nerve at the proximal end of the lesion, and searched for sprouts in the injured domain. These isolated axons regrew centralward as supported by ultrastructure, labelling with horseradish peroxidase, and staining with Dil. This result indicates that: (i) axons embody a post transcriptional sprouting programme; (ii) resident cells of the nerve, probably Schwann cells, repress this programme, and (III) navigation of regrowing axons is determined by the environment. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved.
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    Local regulation of the axonal phenotype, a case of merotrophism
    (2005) Court, FA; Alvarez, J
    In this essay, we show that several anatomical features of the axon, namely, microtubular content, caliber and extension of sprouts, correlate on a local basis with the particular condition of the glial cell, i.e., the anatomy of axons is dynamic, although it is seen usually in its 'normal' state. The occurence of ribosomes and messenger RNAs in the axon suggests that exoplasmic proteins are most likely synthesized locally, at variance with the accepted notion that they are supplied by the cell body. We propose that the supporting cell (oligodendrocyte or Schwann cell) regulates the axonal phenotype by fine-tuning the ongoing axonal protein synthesis.
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    Nerve regeneration in Wlds mice is normalized by actinomycin D
    (2000) Court, F; Alvarez, J
    Injured nerves of Wld(s) mice neither degenerate nor regenerate for several weeks. We have conjectured that Wld(s) axons have the ability to regenerate but its expression is impaired by the Schwann cells of the undegenerated distal stump. To test this conjecture, transcription was locally arrested with actinomycin D (ActD), nerves were crushed, and regrowth was evaluated. In normal CD1 nerves injected with ActD 3 days before the crush. the rate of elongation was not affected but the delay of regrowth was shortened. In sharp contrast, ActD normalized the elongation of Wld(s) axons. When Wld(s) nerves were crushed past the treated segment, axons did not regenerate. After 7, but not 4, days of treatment, intact CD1 and Wld(s) axons presented a local sprouting response. We conclude that Wld(s) axons can regenerate in a normal way but do not do so because the undegenerated Schwann cells of the distal stump repress the regrowth program. We present a model axon that includes a destruction program and a post-transcriptional trophic regulation of its phenotype. (C) 2000 Elsevier Science B.V. All rights reserved.
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    Peripheral axons of Wlds mice, which regenerate after a delay of several weeks, do so readily when transcription is inhibited in the distal stump
    (1998) Benavides, E; Alvarez, J
    We have raised the hypothesis that differentiated Schwann cells repress regrowth of axons but become permissive upon dedifferentiation. Wld(s) mouse is a strain in which severed peripheral nerves do not degenerate for several weeks, and axonal regeneration does not occur either [5,11]. In this strain, we studied the role of resident cells upon axonal regeneration by inhibiting transcription. Regeneration was assessed with the pinch test, electron microscopy and Dil (a fluorescent lipid soluble dye). After a crush, Wlds axone did not regenerate but they did so when the crush was made through a nerve segment treated with actinomycin D (ActD), an inhibitor of transcription. In contrast, when the crush was made distal to the treated segment no regeneration ensued. Our results support the notion that normal resident cells of peripheral nerves repress axonal growth. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserved.
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    The autonomous axon: a model based on local synthesis of proteins
    (2001) Alvarez, J
    In the current understanding of axons, axoplasmic synthesis of proteins is negated, and it is asserted that proteins are transported from perikarya to axons. This 'transport model' in which axons are fully dependent of perikarya is seriously flawed. The 'autonomous axon' proposed here negates in turn transport of proteins, and asserts (i) local synthesis of axoplasmic proteins, corner stone of this model, (ii) existence of internal programs in axon and terminals, (iii) external control of programs resulting in local regulation of phenotype of axons and terminals, hence they are autonomous from perikarya; (iv) participation of perikarya through the fast transport in setting up the axonal programs but not in their immediate regulation. The word merotrophism (meros meaning part) denotes post-transcriptional regulation of phenotype of restricted regions of a cell. We surmise that merotrophism is at the base of many plastic phenomena.