Decreased expression of the embryonic form of the neural cell adhesion molecule in schizophrenic brains.

Barbeau, David; Liang, Jin Jun; Robitalille, Y; Quirion, Rémi; Srivastava, Lalit K.

doi:10.1073/pnas.92.7.2785

Cited by 299 publications

(176 citation statements)

References 40 publications

(48 reference statements)

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“…Such environmental or pharmacological intervention may prove highly relevant in certain disease states with well defined times of onset. For example, the expression of NCAM PSA is reduced in the hippocampal dentate of schizophrenic patients suggestive of a deficit in memory associated synaptic plasticity mechanisms (Barbeau et al, 1995). Thus, the benefits accruing from such procognitive interventions have the potential to oppose and even reverse aberrant synaptic connectivity patterning that likely underlie the developmental emergence of disorders such as autism, schizophrenia, and Alzheimer's disease (Braak and Braak, 1991;Bobinski et al, 1995;Scheff et al, 1996;Feinberg, 1982;Hoffman and McGlashan, 1997;Mirnics et al, 2001;Volkmar and Pauls, 2003).…”

Section: Discussionmentioning

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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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%

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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“…This form of NCAM has been proposed to be related to synaptic rearrangement and plasticity (Barbeau et al, 1995). (ii) Selective displacement of interstitial white matter neurons in the frontal lobes of schizophrenics that may reflect an alteration in the migration of subplate neurons or in the pattern of programmed cell death.…”

Section: Theoretical Neurobiologymentioning

confidence: 99%

The disconnection hypothesis

Friston

1998

Schizophrenia Research

781

466

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This article reviews the disconnection hypothesis of schizophrenia and presents a mechanistic account of how dysfunctional integration among neuronal systems might arise. This neurobiological account is based on the central role played by neuronal plasticity in shaping the connections and the ensuing dynamics that underlie brain function. The particular hypothesis put forward here is that the pathophysiology of schizophrenia is expressed at the level of modulation of associative changes in synaptic efficacy; specifically the modulation of plasticity in those brain systems responsible for emotional learning and memory, in the post-natal period. This modulation is mediated by ascending neurotransmitter systems that: (i) have been implicated in schizophrenia; and (ii) are known to be involved in consolidating synaptic connections during learning. The proposed pathophysiology would translate, in functional terms, into a disruption of the reinforcement of adaptive behaviour that is consistent with the disintegrative aspects of schizophrenic neuropsychology.

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“…[2][3][4]7 Autopsy studies of schizophrenic brains have found evidence of disturbed neuronal formation and migration, [8][9][10] abnormal expression of developmentally-regulated molecules such as NCAM, 11 and a lack of gliosis in brain regions exhibiting cell loss. 7,12 Of note, abnormal levels of an NCAM isoform have been found in the CSF of schizophrenia patients.…”

Section: Human and Epidemiological Studiesmentioning

confidence: 99%

Schizophrenia and viral infection during neurodevelopment: a focus on mechanisms

Pearce

2001

Mol Psychiatry

135

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The task of defining schizophrenia pathogenesis has fascinated and frustrated researchers for nearly a century. In recent years, unprecedented advances from diverse fields of study have given credence to both viral and developmental theories. This review considers possible mechanisms by which viral and developmental processes may interact to engender schizophrenia. Many of the current controversies in schizophrenia pathogenesis are reviewed in light of the viral hypothesis, including: epidemiological findings and the role of a genetic diathesis, phenotype heterogeneity, abnormalities in excitatory and inhibitory neurotransmitter systems, anomalous cerebral latereralization, and static vs progressive disease. The importance of animal models in elucidating the impact of viral infections on developing neurons is illustrated by recent studies in which neonatal rats are infected with lymphocytic choriomeningitis virus in order to examine alterations in hippocampal circuitry. Finally, consideration is given to a new hypothesis that some cases of schizophrenia could be instigated by a viral infection that disrupts developing inhibitory circuits, consequently unleashing glutamatergic neurotransmission leading to selective excitotoxicity, and a degenerative disease course. Molecular Psychiatry (2001) 6, 634-646.

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Decreased expression of the embryonic form of the neural cell adhesion molecule in schizophrenic brains.

Cited by 299 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

The disconnection hypothesis

Schizophrenia and viral infection during neurodevelopment: a focus on mechanisms

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