Monosialoganglioside GM1 reduces NMDA neurotoxicity in neonatal rat brain

Lipartiti, Maria; Lazzaro, A.; Zanoni, R.; Mazzari, S.; Toffano, G.; Leon, Alberta

doi:10.1016/0014-4886(91)90019-9

Cited by 32 publications

(17 citation statements)

References 18 publications

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“…It remains to be decided whether the effects of this oxysterol on reactive astrocytes we have evidenced here are all inter-related and all contribute to the permeability sterol, had no decreasing effect on the astrocytic reaction whatever the neuroprotective effect of this molecule (Jonsson et al, 1984;Ledeen, 1984;Toffano et al, 1984;Lipartiti et al, 1991;Saqr et al, 1993).…”

Section: Discussionmentioning

confidence: 90%

Oxystdrol (7β‐hydroxycholestesteryl‐3‐oleate) promotes serotonergic reinnervation in the lesioned rat spinal cord by reducing glial reaction

Ribotta

Rajaofetra

Morin-Richaud

et al. 1995

J of Neuroscience Research

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In the present study, following previous experience with electrolytic lesion of the rat brain, and subsequent reduction of reactive gliosis with 7 beta-hydroxycholesterol derivatives (Bochelen et al.: Neuroscience 51:827-834, 1992), we have performed a hemisection of the spinal cord in adult rats and investigated the influence of 7 beta-hydroxycholesteryl-3-oleate (oxysterol) on the intensity of the astrocytic reaction and the axonal regeneration. We have shown here that local administration of liposomes containing this oxysterol reduced the intensity of the astroglial reaction on the sectioned side, as seen with immunocytochemical detection of glial fibrillary acidic protein (GFAP) and by in situ hybridization with a specific RNA probe. Moreover, radioautographic evaluation of astrocyte proliferation with tritiated thymidine evidenced a reduction of the astrocyte labelling index. In addition, double immunocytochemical detection of GFAP and polysialylated neural cell adhesion molecule (E-NCAM) revealed a decrease of the expression of this molecule in reactive astrocytes of the treated animals. Finally, immunocytochemical detection of serotonin (5HT) was determined in the raphespinal projections, which constitute a major descending system. In treated animals, serotonergic axons originating from the intact side reinnervated the dorsal horn of the sectioned side, below the hemisection. These results demonstrate that 7 beta-hydroxycholesteryl-3-oleate can reduce the astrocytic reaction following spinal cord injury, promoting the serotonergic reinnervation of a denervated territory.

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Section: Discussionmentioning

confidence: 90%

Oxystdrol (7β‐hydroxycholestesteryl‐3‐oleate) promotes serotonergic reinnervation in the lesioned rat spinal cord by reducing glial reaction

Ribotta

Rajaofetra

Morin-Richaud

et al. 1995

J of Neuroscience Research

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“…The above facts raise the possibility that GM1 interaction with cholinergic system is indirect via dopaminergic systems. Alternatively, interactions between acetylcholine and glutamate have been suggested in the modulation of memory processes (Aigner 1995) and it has been shown that GM1 treatment can prevent glutamate-mediated neurotoxicity in vitro (Favaron et al 1988;De Erauskin et al 1990) and in vivo (Lipartiti et al 1991;Lombardi and Moroni 1992). The participation of other transmitter systems in the effect of GM1 cannot therefore be excluded.…”

Section: Discussionmentioning

confidence: 93%

Ganglioside GM1 attenuates scopolamine-induced amnesia in rats and mice

1999

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Some experimental evidence suggests that the beneficial effects of monosialoganglioside GM1 on learning and memory could be related to an improving effect in central cholinergic function. The present study investigates the effects of GM1 on the memory impairment induced by scopolamine in rats or mice tested in passive (PA) and discriminative avoidance (DA) tasks, respectively. Wistar EPM-1 male rats and Swiss EPM-M1 male mice were treated daily IP with 50 mg/kg GM1 or saline for 7 or 14 days, respectively. Twenty-four hours after the last injection, GM1-treated animals received 1 mg/kg scopolamine (GM1-SCO) and saline-treated animals received 1 mg/kg scopolamine (SAL-SCO) or saline (SAL-SAL) IP. Twenty minutes later, the animals were submitted to PA or DA conditioning, and tests were performed 24 h later. The latency in entering the dark chamber of the PA apparatus (LD) presented by SAL-SCO rats was significantly decreased when compared to that presented by SAL-SAL animals. GM1-SCO animals showed an increased LD when compared to SAL-SCO animals and were not significantly different from SAL-SAL rats. GM1-SCO and SAL-SAL (but not SAL-SCO) mice spent significantly less time in the aversive enclosed arm of the discriminative avoidance apparatus when compared to the time spent in the non-aversive enclosed arm. The results are consistent with the interpretation that GM1 attenuates scopolamine-induced amnesia. Although not eliminating the participation of other transmitter systems, the present study indicates a possible role of central cholinergic transmission in the action of this compound on learning and memory.

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“…Depending on the cellular context, Ca 2+ influx through voltage-sensitive Ca 2+ channels increased cell survival, whereas Ca 2+ influx via the NMDA receptors in postnatal neurons mediated excitotoxic cell death [102][103][104]. The peak susceptibility to NMDA-mediated excitotoxicity occurred between P7 and P15, from accentuation of its metabolic effects [105,106] or reduction of the voltage-dependent Mg 2+ block [107], potentially correlated with the expression of NMDA subunits in immature neurons [108]. Permanent alterations in the structure of NMDA receptors occurred following exposure to neonatal hypoxic stress, resulting in increased susceptibility to NMDA-induced toxicity thereafter [109,110].…”

Section: Mechanisms Of Neonatal Brain Plasticitymentioning

confidence: 99%

Can Adverse Neonatal Experiences Alter Brain Development and Subsequent Behavior?

Anand

Scalzo²

2000

Neonatology

538

316

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Self-destructive behavior in current society promotes a search for psychobiological factors underlying this epidemic. Perinatal brain plasticity increases the vulnerability to early adverse experiences, thus leading to abnormal development and behavior. Although several epidemiological investigations have correlated perinatal and neonatal complications with abnormal adult behavior, our understanding of the underlying mechanisms remains rudimentary. Models of early experience, such as repetitive pain, sepsis, or maternal separation in rodents and other species have noted multiple alterations in the adult brain, correlated with specific behavioral phenotypes depending on the timing and nature of the insult. The mechanisms mediating such changes in the neonatal brain have remained largely unexplored. We propose that lack of N-methyl-D-aspartate (NMDA) receptor activity from maternal separation and sensory isolation leads to increased apoptosis in multiple areas of the immature brain. On the other hand, exposure to repetitive pain may cause excessive NMDA/excitatory amino acid activation resulting in excitotoxic damage to developing neurons. These changes promote two distinct behavioral phenotypes characterized by increased anxiety, altered pain sensitivity, stress disorders, hyperactivity/attention deficit disorder, leading to impaired social skills and patterns of self-destructive behavior. The clinical important of these mechanisms lies in the prevention of early insults, effective treatment of neonatal pain and stress, and perhaps the discovery of novel therapeutic approaches that limit neuronal excitotoxicity or apoptosis.

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Monosialoganglioside GM1 reduces NMDA neurotoxicity in neonatal rat brain

Cited by 32 publications

References 18 publications

Oxystdrol (7β‐hydroxycholestesteryl‐3‐oleate) promotes serotonergic reinnervation in the lesioned rat spinal cord by reducing glial reaction

Oxystdrol (7β‐hydroxycholestesteryl‐3‐oleate) promotes serotonergic reinnervation in the lesioned rat spinal cord by reducing glial reaction

Ganglioside GM1 attenuates scopolamine-induced amnesia in rats and mice

Can Adverse Neonatal Experiences Alter Brain Development and Subsequent Behavior?

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