PSA–NCAM Is Required for Activity-Induced Synaptic Plasticity

Michelet, Dominique; Wang, C.; Skibo, G. G.; Toni, Nicolas; Cremer, Harold; Calaora, Viviane; Rougon, Geneviève; Kiss, József Zoltán

doi:10.1016/s0896-6273(00)80174-9

Cited by 555 publications

(439 citation statements)

References 40 publications

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“…Given that expression of polysialylated NCAM is a prerequisite for activity-dependent synaptic plasticity (Muller et al, 1996;Theodosis et al, 1999), it is perhaps not surprising that enhancing cholinergic function, long known to be necessary for memory consolidation (Doyle and Regan, 1993;Everitt and Robbins, 1997;Milner et al, 1998), modulates expression of this neuroplastic mechanism. Tacrine directly enhances acetylcholine transmission by inhibition of AChE while deprenyl will increase acetylcholine activity indirectly via improved dopamine function (Tariot et al, 1987;Piccinin et al, 1990;Mangoni et al, 1991;Molinengo and Ghi, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…For example, the neural cell adhesion molecule (NCAM) is necessary for activity-dependent synaptic plasticity, such as that associated with hippocampal long-term potentiation (LTP) and avoidance conditioning and spatial learning paradigms (Doyle et al, 1992;Lüthi et al, 1994;R nn et al, 1995;Alexinsky et al, 1997). Glycosylation of NCAM with extended chains of a2,8-linked polysialic acid (PSA) is also necessary for memory consolidation as their cleavage with endoneuraminidase prevents LTP and spatial learning (Becker et al, 1996;Muller et al, 1996;Kleene and Schachner, 2004). Within the hippocampus, a transient increase in polysialylation of neurons located at the dentate infragranular zone at 10-12 h following learning is necessary for memory consolidation (Fox et al, 1995;Murphy et al, 1996;Foley et al, 2003;Sandi et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Chronic Exposure of Rats to Cognition Enhancing Drugs Produces a Neuroplastic Response Identical to that Obtained by Complex Environment Rearing

Murphy

Foley

O’Connell

et al. 2005

Neuropsychopharmacol

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Recent data suggest that Alzheimer's patients who discontinue treatment with cholinesterase inhibitors have a significantly delayed cognitive decline as compared to patients receiving placebo. Such observations suggest cholinesterase inhibitors to provide a diseasemodifying effect as well as symptomatic relief and, moreover, that this benefit remains after drug withdrawal. Consistent with this suggestion, we now demonstrate that chronic administration of tacrine, nefiracetam, and deprenyl, drugs that augment cholinergic function, increases the basal frequency of dentate polysialylated neurons in a manner similar to the enhanced neuroplasticity achieved through complex environment rearing. While both drug-treated and complex environment reared animals continue to exhibit memoryassociated activation of hippocampal polysialylated neurons, the magnitude is significantly reduced suggesting that such interventions induce a more robust memory pathway that can acquire and consolidate new information more efficiently. This hypothesis is supported by our findings of improved learning behavior and enhanced resistance to cholinergic deficits seen following either intervention. Furthermore, the level of enhancement of basal neuroplastic status achieved by either drug or environmental intervention correlates directly with improved spatial learning ability. As a combination of both interventions failed to further increase basal polysialylated cell frequency, complex environment rearing and chronic drug regimens most likely enhanced cognitive performance by the same mechanism(s). These findings suggest that improved memory-associated synaptic plasticity may be the fundamental mechanism underlying the disease modifying action of drugs such as cholinesterase inhibitors. Moreover, the molecular and cellular events underpinning neuroplastic responses are identified as novel targets in the search for interventive drug strategies for the treatment of neurodegenerative and neuropsychiatric disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chronic Exposure of Rats to Cognition Enhancing Drugs Produces a Neuroplastic Response Identical to that Obtained by Complex Environment Rearing

Murphy

Foley

O’Connell

et al. 2005

Neuropsychopharmacol

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“…Later studies reported that, as adults, these NCAM-null mutants showed a reduction in thorny excrescences in CA3 pyramidal cells, as well as alterations in mossy fiber growth and fasciculation Cremer et al, 1998). As adults, the exploratory behavior of these null mutant mice, their spatial learning, fear conditioning, and LTP were inferior to those of the wildtype, and the mice were characterized by increased aggressiveness as well as alterations in emotional/motivational behavior and hyperresponsiveness of the serotonergic system (Muller et al, 1996;Stork et al, 1997Stork et al, , 1999Stork et al, , 2000. Interestingly, in these mutants, 'anxious' behaviors, but not learning, could be rescued through a transgenic manipulation causing reexpression of the NCAM-180 kDa isoform (Stork et al, 2000).…”

Section: Exposure To Stress During Juvenility Alters Emotional Responmentioning

confidence: 99%

Exposure to Stressors during Juvenility Disrupts Development-Related Alterations in the PSA-NCAM to NCAM Expression Ratio: Potential Relevance for Mood and Anxiety Disorders

Tsoory

Guterman

Richter‐Levin

2007

Neuropsychopharmacol

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Childhood trauma is associated with higher rates of both mood and anxiety disorders in adulthood. The exposure of rats to stressors during juvenility has comparable effects, and was suggested as a model of induced predisposition for these disorders. The neural cell adhesion molecule (NCAM) and its polysialylated form PSA-NCAM are critically involved in neural development, activity-dependent synaptic plasticity, and learning processes. We examined the effects of exposure to stressors during juvenility on coping with stressors in adulthood and on NCAM and PSA-NCAM expression within the rat limbic system both soon after the exposure and in adulthood. Exposure to stressors during juvenility reduced novel-setting exploration and impaired two-way shuttle avoidance learning in adulthood. Among naive rats, a development-related decrease of about 50% was evident in the PSA-NCAM to NCAM expression ratio in the basolateral amygdala, in the CA1 and dentate gyrus regions of the hippocampus, and in the entorhinal cortex. In juvenile-stressed rats, we found no such decrease, but rather an increase in the polysialylation of NCAM (B50%), evident soon after the exposure to juvenile stress and also in adulthood. Our results suggest that exposure to stressors during juvenility alters the maturation of the limbic system, and potentially underlies the predisposition to exhibit stress-related symptoms in adulthood.

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“…Although PSA-NCAM disappears from most of the CNS after early postnatal development it continues to be expressed in regions of the brain capable of cellular remodeling and neurogenesis, including the granule cell layer of the hippocampus. PSA-NCAM is reported to play a role in long-term potentiation and other forms of activity dependent cellular remodeling (see Muller et al 1996;Becker et al 1996).…”

Section: Colocalization Of Phospho-creb With Markers Of Maturing Neuronsmentioning

confidence: 99%

Regulation of Adult Neurogenesis by Antidepressant Treatment

Duman

Nakagawa

Malberg

2001

Neuropsychopharmacology

423

249

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Demonstration of neurogenesis in adult brainOur understanding of how the brain functions and undergoes adaptation and plasticity has changed dramatically over the past several years. A great deal of work has demonstrated that altered levels of neurotransmitters, second messenger pathways, and gene expression profiles underlie cellular and behavioral plasticity. This includes models of learning and memory as well as models of depression, anxiety, and psychosis, and the long-term actions of psychotropic drugs. However, it is now becoming increasing evident that changes in cellular morphology and even more pronounced alterations in brain structure also contribute to neural plasticity or remodeling. At the cellular level these changes can occur in the form of up or down-regulation of synapse formation and spine density or extension and retraction of dendrites. Another very dramatic example is up or down-regulation of neurogenesis in adult brain. Studies in recent years demonstrate that new cell birth occurs in adult brain and that the rate of neurogenesis and the survival of new neurons is regulated by a number of environmental, endocrine, and pharmacological treatments.In this paper we discuss the evidence that structural remodeling may be involved in the pathophysiology and treatment of mood disorders. The potential role of neurogenesis is also discussed as well as the molecular mechanisms which underlie antidepressant regulation of new cell birth and survival. The studies to date suggest an exciting possibility for the role of neurogenesis

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PSA–NCAM Is Required for Activity-Induced Synaptic Plasticity

Cited by 555 publications

References 40 publications

Chronic Exposure of Rats to Cognition Enhancing Drugs Produces a Neuroplastic Response Identical to that Obtained by Complex Environment Rearing

Chronic Exposure of Rats to Cognition Enhancing Drugs Produces a Neuroplastic Response Identical to that Obtained by Complex Environment Rearing

Exposure to Stressors during Juvenility Disrupts Development-Related Alterations in the PSA-NCAM to NCAM Expression Ratio: Potential Relevance for Mood and Anxiety Disorders

Regulation of Adult Neurogenesis by Antidepressant Treatment

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