Abstract
The neural cell adhesion molecule (NCAM) is a glycoprotein implicated in cell–cell adhesion, neurite outgrowth and synaptic plasticity. Polysialic acid (polySia) is mainly attached to NCAM (polySia-NCAM) and has an essential role in regulating NCAM-dependent developmental processes that require plasticity, that is, cell migration, axon guidance and synapse formation. Post-mortem and genetic evidence suggests that dysregulation of polySia-NCAM is involved in schizophrenia (SZ). We enrolled 45 patients diagnosed with SZ and 45 healthy individuals who were submitted to polySia-NCAM peripheral quantification, cognitive and psychopathological assessment and structural neuroimaging (brain volumes and diffusion tensor imaging). PolySia-NCAM serum levels were increased in SZ patients, independently of antipsychotic treatment, and were associated with negative symptoms, blunted affect and declarative memory impairment. The increased polySia-NCAM levels were associated with decreased volume in the left prefrontal cortex, namely Brodmann area 46, in patients and increased volume in the same brain area of healthy individuals. As this brain region is involved in the pathophysiology of SZ and its associated phenomenology, the data indicate that polySia-NCAM deserves further scrutiny because of its possible role in early neurodevelopmental mechanisms of the disorder.
Highlights
Development of brain connectivity requires temporal and spatial control of cellular interactions
previous report indicated that the serum levels structure before the onset
related to those found in the brains of SZ patients
Summary
Development of brain connectivity requires temporal and spatial control of cellular interactions. When polySia is present on NCAM it acts as a negative regulator of cell interactions associated with a variety of developmental processes that require plasticity, including cell migration, the guidance and targeting of axons and synapse formation.[2,3] The loss of polySia-NCAM (polySia attached to NCAM) in NCAM-deficient mice or in wild-type mice treated with a polySia-specific endosialidase has been associated with alterations in a variety of brain functions, including learning and memory behaviors and both long-term potentiation and longterm depression in the hippocampus.[4] Imbalanced synthesis of polySia and NCAM causes pathological brain development, including reduction of prefrontal cortex (PFC) interneurons, hypoplasia of major brain axon tracts, enlarged ventricles, reduced size of the thalamus and disturbed thalamus–cortex connectivity, which may be linked to the deficits in the cognitive performance observed in these mice.[5,6,7] a synergistic negative consequence of polySia deficiency and cannabis exposure on cognitive performance has been demonstrated,[8] and in a doublehit animal model of schizophrenia (SZ) prefrontal changes of polySia were detected together with altered excitatory–inhibitory balance.[9]
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