Nerve Growth Factor and the Monosialoganglioside GM1: Analogous and Different in Vivo Effects on Biochemical, Morphological, and Behavioral Parameters of Adult Cortically Lesioned Rats

Garofalo, L.; Cuello, A. Claudio

doi:10.1006/exnr.1994.1024

Cited by 56 publications

(24 citation statements)

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“…This finding differs from studies on AD patients, which have shown that modification of the cholinergic inputs in the cortex is the result of either death or atrophy of the basal forebrain cholinergic neurons (Perry et al, 1978;Whitehouse et al, 1982;Pearson et al, 1983;Katzman, 1986). The lack of cell body atrophy could be related to the fact that massive loss of cerebral cortex tissue is required to provoke somatodendritic atrophy in the nucleus basalis Garofalo and Cuello, 1994). Therefore, a higher level of cortical pathology is required to elicit a retrograde involvement of the cholinergic basalocortical projection.…”

Section: Discussioncontrasting

confidence: 58%

Reorganization of Cholinergic Terminals in the Cerebral Cortex and Hippocampus in Transgenic Mice Carrying Mutated Presenilin-1 and Amyloid Precursor Protein Transgenes

et al. 1999

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Cholinergic deficits are one of the most consistent neuropathological landmarks in Alzheimer's disease (AD). We have examined transgenic mouse models (PS1 M146L , APP K670N,M671L ) and a doubly transgenic line (APP K670N,M671L ϩ PS1 M146L ) that overexpress mutated AD-related genes [presenilin-1 (PS1) and the amyloid precursor protein (APP)] to investigate the effect of AD-related gene overexpression and/or amyloidosis on cholinergic parameters.The size of the basal forebrain cholinergic neurons and the pattern of cholinergic synapses in the hippocampus and cerebral cortex were revealed by immunohistochemical staining for choline acetyltransferase and the vesicular acetylcholine transporter, respectively. At the time point studied (8 months), no apparent changes in either the size or density of cholinergic synapses were found in the PS1 M146L mutant relative to the nontransgenic controls. However, the APP K670N,M671L mutant showed a significant elevation in the density of cholinergic synapses in the frontal and parietal cortices. Most importantly, the double mutant (APP K670N,M671L ϩ PS1 M146L ), which had extensive amyloidosis, demonstrated a prominent diminution in the density of cholinergic synapses in the frontal cortex and a reduction in the size of these synapses in the frontal cortex and hippocampus. Nonetheless, no significant changes in the size of basal forebrain cholinergic neurons were observed in these three mutants. This study shows a novel role of APP and a synergistic effect of APP and PS1 that correlates with amyloid load on the reorganization of the cholinergic network in the cerebral cortex and hippocampus at the time point studied.

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Section: Discussioncontrasting

confidence: 58%

Reorganization of Cholinergic Terminals in the Cerebral Cortex and Hippocampus in Transgenic Mice Carrying Mutated Presenilin-1 and Amyloid Precursor Protein Transgenes

et al. 1999

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“…Twelve 8,500-m basalis magnocellularis (NBM) were visualized and analyzed with the same system that was used for the presynaptic boutons, with a 20ϫ objective. For analysis of the NBM, a total of six sections from the midbasalis were taken from each animal as described (12). Three random fields for each level were quantified.…”

Section: Morphometric Analysismentioning

confidence: 99%

“…These areas are the major targets of ascending projections from cholinergic basal forebrain neurons that retrogradely transport NGF from these areas to the cholinergic cell bodies of the basal forebrain (9,10). The intracerebral application of NGF prevents the downregulation of cholinergic markers in septal cholinergic neurons after axotomy (11) and ameliorates both cholinergic and behavioral deficits after basalocortical lesions (12,13).…”

mentioning

confidence: 99%

A nerve growth factor mimetic TrkA antagonist causes withdrawal of cortical cholinergic boutons in the adult rat

Debeir

Cuello

1999

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

109

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Cholinergic neurons respond to the administration of nerve growth factor (NGF) in vivo with a prominent and selective increase of choline acetyl transferase activity. This suggests the possible involvement of endogenous NGF, acting through its receptor TrkA, in the maintenance of central nervous system cholinergic synapses in the adult rat brain. To test this hypothesis, a small peptide, C(92-96), that blocks NGF-TrkA interactions was delivered stereotactically into the rat cortex over a 2-week period, and its effect and potency were compared with those of an anti-NGF monoclonal antibody (mAb NGF30). Two presynaptic antigenic sites were studied by immunoreactivity, and the number of presynaptic sites was counted by using an image analysis system. Synaptophysin was used as a marker for overall cortical synapses, and the vesicular acetylcholine transporter was used as a marker for cortical cholinergic presynaptic sites. No significant variations in the number of synaptophysin-immunoreactive sites were observed. However, both mAb NGF30 and the TrkA antagonist C(92-96) provoked a significant decrease in the number and size of vesicular acetylcholine transporter-IR sites, with the losses being more marked in the C(92-96) treated rats. These observations support the notion that endogenously produced NGF acting through TrkA receptors is involved in the maintenance of the cholinergic phenotype in the normal, adult rat brain and supports the idea that NGF normally plays a role in the continual remodeling of neural circuits during adulthood. The development of neurotrophin mimetics with antagonistic and eventually agonist action may contribute to therapeutic strategies for central nervous system degeneration and trauma.Nerve growth factor (NGF) is the first well characterized member of a family of neurotrophic factors (NTFs) (1) that includes brain-derived neurotrophic factor, neurotrophin 3, and neurotrophin 4 (2, 3). These neurotrophins are known to regulate the survival, differentiation, and phenotypic maintenance of specific neuronal populations, but their role in neuronal plasticity is not fully understood. Investigations in newborn and adult rats have shown that cholinergic neurons in the corpus striatum and those in the basal forebrain projecting to the hippocampus and cortex respond to exogenous NGF with a selective and prominent increase of choline acetyl transferase (ChAT) activity (4-8). These areas are the major targets of ascending projections from cholinergic basal forebrain neurons that retrogradely transport NGF from these areas to the cholinergic cell bodies of the basal forebrain (9, 10). The intracerebral application of NGF prevents the downregulation of cholinergic markers in septal cholinergic neurons after axotomy (11) and ameliorates both cholinergic and behavioral deficits after basalocortical lesions (12, 13).Another cholinergic phenotype-specific protein is the vesicular acetylcholine transporter (VAChT) (14). This molecule mobilizes cytosolic acetylcholine (ACh) into the synaptic vesicle...

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“…It was reported that GM1 could protect cerebral ischemia in vivo and in vitro, one protective mechanism of which is that GM1 could reduce neural injury induced by toxicity of excitatory amino acid via N-methyl-D-aspartate receptor (NMDAR) (Kharlamov et al, 1993;Simon et al, 1993;Garofalo and Cuello, 1994;de Erausquin et al, 1990). NMDAR is a kind of ionotrophic glutamate receptor, a receptor gated Ca 2+ channel, and is extensively distributed in the central nervous system (CNS).…”

Section: Introductionmentioning

confidence: 99%

GM1 stabilizes expression of NMDA receptor subunit 1 in the ischemic hemisphere of MCAo/reperfusion rat

Liu

Ding

Wei

et al. 2005

J. Zhejiang Univ. Sci.

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Liu et al. / J ZhejiangAbstract: Objective: To determine the protective effect of monosialoganglionside (GM1) and evaluate the influence of GM1 on expression of N-methyl-D-aspartate receptor subunit 1 (NMDAR1) in Sprague-Dawley (SD) rats with focal cerebral ischemia-reperfusion (I/R). Methods: Left middle cerebral artery (MCA) was occluded by an intraluminal suture for 1 h and the brain was reperfused for 72 h in SD rats when infarct volume was measured, GM1 (10 mg/kg) was given ip (intraperitoneally) at 5 min (group A), 1 h (group B) and 2 h (group C) after MCA occlusion (MCAo). Expression of NMDAR1 was detected by Western blot at various time after reperfusion (4 h, 6 h, 24 h, 48 h and 72 h) in ischemic hemispheres of the rats with or without GM1 administered. Results: (1) Adjusted relative infarct volumes of groups A and B were significantly smaller than that of group C and the control group (P<0.01 and P<0.05, respectively). (2) Expression level of NMDAR1 was temporally high at 6 h after reperfusion, and dipped below the normal level at 72 h after reperfusion. GM1 at 5 min after MCAo significantly suppressed the expression of NMDAR1 at 6 h after reperfusion (P<0.05 vs the control). At 72 h after reperfusion, the NMDAR1 expression level of rats treated with GM1 administered (at 5 min or 2 h after MCAo) was significantly higher than that of the control (P<0.05). Conclusion: GM1 can time-dependently reduce infarct volume in rats with focal cerebral I/R partly through stabilizing the expression of NMDAR1.

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Nerve Growth Factor and the Monosialoganglioside GM1: Analogous and Different in Vivo Effects on Biochemical, Morphological, and Behavioral Parameters of Adult Cortically Lesioned Rats

Cited by 56 publications

References 0 publications

Reorganization of Cholinergic Terminals in the Cerebral Cortex and Hippocampus in Transgenic Mice Carrying Mutated Presenilin-1 and Amyloid Precursor Protein Transgenes

Reorganization of Cholinergic Terminals in the Cerebral Cortex and Hippocampus in Transgenic Mice Carrying Mutated Presenilin-1 and Amyloid Precursor Protein Transgenes

A nerve growth factor mimetic TrkA antagonist causes withdrawal of cortical cholinergic boutons in the adult rat

GM1 stabilizes expression of NMDA receptor subunit 1 in the ischemic hemisphere of MCAo/reperfusion rat

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