Nitric oxide synthase in motor neurons after axotomy.

Yu, Wan-hua Amy

doi:10.1177/42.4.7510317

Cited by 143 publications

(69 citation statements)

References 3 publications

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“…The expression of nitric oxide synthase (NOS), an enzyme for synthesis of the free radical nitric oxide (NO), can be induced in adult rat motoneurons following both spinal root avulsion (20,22) and cranial nerve axotomy (23), and it has been suggested that the cell death following these lesions may be induced by oxidative stress and reactive oxygen species such as NO (20)(21)(22).…”

mentioning

confidence: 99%

Rescue of adult mouse motoneurons from injury-induced cell death by glial cell line-derived neurotrophic factor.

Wu²,

Lin³

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

333

195

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Glial cell line-derived neurotrophic factor (GDNF) has been shown to rescue developing motoneurons in vivo and in vitro from both naturally occurring and axotomyinduced cell death. To test whether GDNF has trophic effects on adult motoneurons, we used a mouse model of injuryinduced adult motoneuron degeneration. Injuring adult motoneuron axons at the exit point of the nerve from the spinal cord (avulsion) resulted in a 70% loss of motoneurons by 3 weeks following surgery and a complete loss by 6 weeks. Half of the loss was prevented by GDNF treatment. GDNF also induced an increase (hypertrophy) in the size of surviving motoneurons. These data provide strong evidence that the survival of injured adult mammalian motoneurons can be promoted by a known neurotrophic factor, suggesting the potential use of GDNF in therapeutic approaches to adultonset motoneuron diseases such as amyotrophic lateral sclerosis.Factors that promote motoneuron survival have potential as therapeutic agents for the treatment of human neurodegenerative diseases (1). It has been shown that several neurotrophic factors, including brain-derived neurotrophic factor (BDNF) (2-4), insulin-like growth factor (I.GF) (5), ciliary neurotrophic factor (6), and glial cell line-derived neurotrophic factor (GDNF) (7-10), can rescue developing motoneurons from both naturally occurring and axotomy-induced cell death. However, whether these trophic factors also play a role in adult motoneuron survival is not known. Because many motoneuron diseases, such as amyotrophic lateral sclerosis, have a late (i.e., adult) onset, it is important to determine whether neurotrophic factors are effective on injured adult motoneurons.Interactions between motoneurons and their target muscles have been extensively investigated. For example, it is known that transection of axons of motoneurons or removal of their target during embryonic and early postnatal development results in massive motoneuron cell loss, whereas axotomy of adult peripheral nerve induces little if any neuronal death (11)(12)(13)(14)(15)(16)(17)(18)(19). A plausible explanation for this difference is that trophic support derived from mature nonneuronal cells (e.g., Schwann cells) associated with the peripheral nerve maintains the survival of adult motoneurons.A different type of lesion, ventral root avulsion, which involves pulling the root out of the spinal cord, induces the death of virtually all motoneurons in the adult rat and provides a good model to examine the response of adult motoneurons to trophic factors (20,21). The expression of nitric oxide synthase (NOS), an enzyme for synthesis of the free radical nitric oxide (NO), can be induced in adult rat motoneurons following both spinal root avulsion (20,22) and cranial nerve axotomy (23), and it has been suggested that the cell death following these lesions may be induced by oxidative stress and reactive oxygen species such as [20][21][22].Although the target dependency of motoneuron survival is diminished in adult animals (15, 18), adult rat m...

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mentioning

confidence: 99%

Rescue of adult mouse motoneurons from injury-induced cell death by glial cell line-derived neurotrophic factor.

Wu²,

Lin³

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

333

195

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“…We sacrificed eight animals at 48 h and eight at 1 wk; always four mice were treated with MSP and four with conditioned medium. Two mice were axotomyzed and treated with saline solution.Mice in which one of the two nerves was resected and treated with saline solution, showed increased NADPH-d reactivity in the axotomized side compared with the contralateral intact one, as described in literature (Yu, 1994). Similarly, NADPH-d reactivity increased in the nucleus ipsilateral to axotomy of mice treated with conditioned medium ( Figure 4A, on left, and C).…”

mentioning

confidence: 48%

“…Together with the loss of cholinergic phenotype, another effect of axon injury in the adult hypoglossal system is an up-regulation of NO synthesis through transcriptional induction of NOS (Yu, 1994). Because MSP represses the production of NO in murine peritoneal macrophages (Wang et al, 1994), we studied whether this function was present in the hypoglossal motoneurons as well.…”

Section: Msp Prevents the Induction Of Nitric-oxide Synthase (Nos) Inmentioning

confidence: 99%

Macrophage Stimulating Protein Is a Novel Neurotrophic Factor

Stella

Vercelli

Repici

et al. 2001

MBoC

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Macrophage stimulating protein (MSP), also known as hepatocyte growth factor-like, is a soluble cytokine that belongs to the family of the plasminogen-related growth factors (PRGFs). PRGFs are ␣/␤ heterodimers that bind to transmembrane tyrosine kinase receptors. MSP was originally isolated as a chemotactic factor for peritoneal macrophages. Through binding to its receptor, encoded by the RON gene, it stimulates dissociation of epithelia and works as an inflammatory mediator by repressing the production of nitric oxide (NO). Here, we identify a novel role for MSP in the central nervous system. As a paradigm to analyze this function we chose the hypoglossal system of adult mice. We demonstrate in vivo that either administration of exogenous MSP or transplantation of MSP-producing cells at the proximal stump of the resected nerve is sufficient to prevent motoneuron atrophy upon axotomy. We also show that the MSP gene is expressed in the tongue, the target of the hypoglossal nerve, and that MSP induces biosynthesis of Ron receptor in the motoneuron somata. Finally, we show that MSP suppresses NO production in the injured hypoglossal nuclei. Together, these data suggest that MSP is a novel neurotrophic factor for cranial motoneurons and, by regulating the production of NO, may have a role in brain plasticity and regeneration. INTRODUCTIONMacrophage stimulating protein (MSP;Skeel et al., 1991;Yoshimura et al., 1993), also known as hepatocyte growth factor-like (Degen et al., 1991), belongs to the family of plasminogen-related growth factors (PRGF; Donate et al., 1994), of which hepatocyte growth factor (HGF) is the prototype. These soluble cytokines share a common structure: they are heterodimeric polypeptides comprising two subunits joined by disulfide bonds, respectively, characterized by the presence of four kringle domains and a nonfunctional serine-protease-like domain (Naldini et al., 1992;Waltz et al., 1997). The PRGF receptors of MSP and HGF identified so far are Ron for MSP (Gaudino et al., 1994) and Met for HGF (Bottaro et al., 1991;Naldini et al., 1991).MSP/hepatocyte growth factor-like was originally isolated as a chemotactic factor for peritoneal macrophages Skeel, 1978, 1979), although it may also act as a mitogen or morphogen in a variety of other cell types such as osteoclasts (Kurihara et al., 1996(Kurihara et al., , 1998, epithelial cells (Medico et al., 1996), hematopoietic precursors (Broxmeyer et al., 1996), and carcinoma cells (Maggiora et al., 1998;Willett et al., 1998). It has been shown that in exudate macrophages MSP inhibits the production of nitric oxide (NO), an inflammatory mediator produced in response to treatment with bacterial lipopolysaccharide or interferon-gamma (Wang et al., 1994;Chen et al., 1998).MSP transcripts are present in the liver and, at a lower amount, in kidney and pancreas (Bezerra et al., 1993;Yoshimura et al., 1993). Transcripts of RON (also known as STK in mouse) are detectable in many different organs during murine development. Relatively late in development, hig...

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“…NADPHd and NOS protein are inducible in term of de novo synthesis in traumatically injured neurons (Wu, 2000). After peripheral axotomy, NOS protein and NOS mRNA increase in some neuronal populations (Verge et al, 1992;Vizzard et al, 1995); moreover, NOS is up-regulated in axotomized motoneurons (Yu, 1994;Yu, 1997;Mü ller and Stoll, 1998;Ma et al, 2000).…”

Section: Nos Induction After Axotomymentioning

confidence: 99%

Nitric oxide synthase in the frog cerebellum: Response of Purkinje neurons to unilateral eighth nerve transection

et al. 2002

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When vestibular damage occurs, nitric oxide synthase (NOS) expression in rat cerebellar flocculus is affected. Since compensation for postural symptoms occurs and Purkinje cells play an important role in movement coordination and motor learning, we analyzed in situ the induction of NOS in the Purkinje cell population of the cerebellum (corpus cerebelli) of frog after unilateral transection of the eighth statoacoustic nerve to gain insight into the role of NO in neural plasticity after injury. Three days after neurectomy, the early effects induced NADPH diaphorase reactivity in most of the Purkinje cells on the ipsilateral side, while on the contralateral side the highest labeling was observed at 15 days. This finding can give information on the dynamics of vestibular compensation, in which NOS involvement was investigated. At 30 days, NADPH diaphorase reactivity was present in a large number of Purkinje cells of the whole cerebellum, while at 60 days a down-regulation for NADPH diaphorase reactivity was evident. A similar trend was observed for NOS-immunoreactivity, which was still present at 60 days in a high percentage of Purkinje cells, mainly on the ipsilateral side. On the basis of cell density evaluations, it was proposed that the early induction of NOS after neurectomy was linked to the degeneration of a part of the Purkinje neurons, while the permanence of NOS labeling might be due to a neuroprotective role of NO in the restoration phase of the vestibular compensation process. Anat Rec 268: 73-83, 2002.

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Nitric oxide synthase in motor neurons after axotomy.

Cited by 143 publications

References 3 publications

Rescue of adult mouse motoneurons from injury-induced cell death by glial cell line-derived neurotrophic factor.

Rescue of adult mouse motoneurons from injury-induced cell death by glial cell line-derived neurotrophic factor.

Macrophage Stimulating Protein Is a Novel Neurotrophic Factor

Nitric oxide synthase in the frog cerebellum: Response of Purkinje neurons to unilateral eighth nerve transection

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