Reduction of Synaptophysin Immunoreactivity in the Prefrontal Cortex of Subjects With Schizophrenia

Glantz, Leisa A.

doi:10.1001/archpsyc.1997.01830190088009

Cited by 142 publications

(58 citation statements)

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“…Inappropriate dendritic arborization, spinogenesis, and synaptic connections lead to inappropriate connectivity and altered excitation-inhibition balance (McGlashan and Hoffman, 2000; Spronsen and Hoogenraad, 2010; Duman and Aghajanian, 2012). This is supported by observations of decreased dendritic spines and synaptic labeling in post mortem cortex of schizophrenic patients (Glantz and Lewis, 1997, 2000; Honer et al, 1999). Thus, synaptogenesis can be altered by any of the previously discussed developmental events and plays an important role in neuropsychiatric disease pathology.…”

Section: Developmental Effects Of Dopaminergic Modulationsupporting

confidence: 68%

Developmental origins of brain disorders: roles for dopamine

Money

Stanwood

2013

Front. Cell. Neurosci.

179

164

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Neurotransmitters and neuromodulators, such as dopamine, participate in a wide range of behavioral and cognitive functions in the adult brain, including movement, cognition, and reward. Dopamine-mediated signaling plays a fundamental neurodevelopmental role in forebrain differentiation and circuit formation. These developmental effects, such as modulation of neuronal migration and dendritic growth, occur before synaptogenesis and demonstrate novel roles for dopaminergic signaling beyond neuromodulation at the synapse. Pharmacologic and genetic disruptions demonstrate that these effects are brain region- and receptor subtype-specific. For example, the striatum and frontal cortex exhibit abnormal neuronal structure and function following prenatal disruption of dopamine receptor signaling. Alterations in these processes are implicated in the pathophysiology of neuropsychiatric disorders, and emerging studies of neurodevelopmental disruptions may shed light on the pathophysiology of abnormal neuronal circuitry in neuropsychiatric disorders.

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Section: Developmental Effects Of Dopaminergic Modulationsupporting

confidence: 68%

Developmental origins of brain disorders: roles for dopamine

Money

Stanwood

2013

Front. Cell. Neurosci.

179

164

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“…As a result, the synaptic architecture of the PFC may remain in an excessively plastic, permanently juvenile state where synapses and thus functional cortical circuits fail to be stabilized, compromising the integrity, stability and fidelity of PFC circuits that are necessary for reliable and predictable information processing and may thereby contribute to the onset of schizophrenia and the persistent symptomatic and cognitive deficits that characterize the course of this chronic debilitating illness. This scenario may, at least in part, explain the previous postmortem findings of decreased dendritic spines and neuropil in subjects with schizophrenia (48, 62, 63). Consistent with this hypothesis, using a novel free-water imaging technique, it has recently been shown that the extracellular space in the cerebral cortex, of which PNNs are a component, was significantly decreased in first-episode schizophrenia patients (64).…”

Section: Discussionmentioning

confidence: 82%

Developmental Pattern of Perineuronal Nets in the Human Prefrontal Cortex and Their Deficit in Schizophrenia

Mauney

Athanas

Pantazopoulos

et al. 2013

Biological Psychiatry

248

260

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Background Perineuronal nets (PNNs) are extracellular matrix structures that enwrap many neurons in the brain. They regulate the postnatal experience-dependent maturation of brain circuits and maintain their functional integrity in the mature brain by stabilizing their synaptic architecture. Methods Eighty-six postmortem human brains were included in this study. We used Wisteria Floribunda agglutinin histochemistry to visualize PNNs to investigate whether the densities of PNNs in the prefrontal cortex (PFC) and primary visual cortex were altered in subjects with schizophrenia or bipolar disorder. In addition, we quantified the normal postnatal development of PNNs in the human PFC. Results Compared to the normal control subjects, the densities of PNNs were decreased by 70–76% in layers 3 and 5 of the PFC in schizophrenia but not in bipolar disorder. This finding was replicated in a separate group of schizophrenia and normal control subjects. In addition, PNN densities in the primary visual cortex were unaltered in either condition. Finally, the number of PNNs in the PFC increased during postnatal development through the peripubertal period until late adolescence and early adulthood. Conclusions These findings suggest that PNN deficit contributes to PFC dysfunction in schizophrenia. The fact that the timing of PNN development overlaps with the period when schizophrenia symptomatology gradually emerges raises the possibility that aberrant PNN formation may contribute to the onset of illness. Thus, characterization of the molecular mechanisms underlying PNN deficit may have important implications for the conceptualization of novel strategies for the diagnosis, treatment, early intervention and prevention of schizophrenia.

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“…Synaptic structural and ultrastructural changes, altered expression of presynaptic proteins, reduction of dendritic spine density, fewer synaptic vesicles and shrinkage of axon boutons have been reported in several brain regions (Eastwood and Harrison, 1995, Perrone Bizzozero et al, 1996, Uranova et al, 1996, Glantz and Lewis, 1997, Garey et al, 1998, Harrison, 1999, Glantz and Lewis, 2000, Mirnics et al, 2000, Rosoklija et al, 2000, Prabakaran et al, 2004, Clark et al, 2006, Camargo et al, 2007, Le-Niculescu et al, 2007, Sweet et al, 2007, Pennington et al, 2008, Smalla et al, 2008, Sweet et al, 2009, Chan et al, 2010, Chu and Liu, 2010, English et al, 2011). Importantly, synaptic abnormalities have been detected in the entorhinal and perirhinal cortices, regions where CSPG changes were also found (Eastwood and Harrison, 1995, Arnold, 1997, Harrison, 1999, Hemby et al, 2002, Law et al, 2004, Beneyto et al, 2007, Pantazopoulos et al, 2010).…”

Section: Ecm Functions Bear Direct Relevance To the Pathophysiologmentioning

confidence: 98%

Extracellular matrix abnormalities in schizophrenia

2012

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Emerging evidence points to the involvement of the brain extracellular matrix (ECM) in the pathophysiology of schizophrenia (SZ). Abnormalities affecting several ECM components, including Reelin and chondroitin sulfate proteoglycans (CSPGs), have been described in subjects with this disease. Solid evidence supports the involvement of Reelin, an ECM glycoprotein involved in corticogenesis, synaptic functions and glutamate NMDA receptor regulation, expressed prevalently in distinct populations of GABAergic neurons, which secrete it into the ECM. Marked changes of Reelin expression in SZ have typically been reported in association with GABA-related abnormalities in subjects with SZ and bipolar disorder. Recent findings from our group point to substantial abnormalities affecting CSPGs, a main ECM component, in the amygdala and entorhinal cortex of subjects with schizophrenia, but not bipolar disorder. Striking increases of glial cells expressing CSPGs were accompanied by reductions of perineuronal nets, CSPG- and Reelin-enriched ECM aggregates enveloping distinct neuronal populations. CSPGs developmental and adult functions, including neuronal migration, axon guidance, synaptic and neurotransmission regulation are highly relevant to the pathophysiology of SZ. Together with reports of anomalies affecting several other ECM components, these findings point to the ECM as a key component of the pathology of SZ. We propose that ECM abnormalities may contribute to several aspects of the pathophysiology of this disease, including disrupted connectivity and neuronal migration, synaptic anomalies and altered GABAergic, glutamatergic and dopaminergic neurotransmission.

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Reduction of Synaptophysin Immunoreactivity in the Prefrontal Cortex of Subjects With Schizophrenia

Cited by 142 publications

References 0 publications

Developmental origins of brain disorders: roles for dopamine

Developmental origins of brain disorders: roles for dopamine

Developmental Pattern of Perineuronal Nets in the Human Prefrontal Cortex and Their Deficit in Schizophrenia

Extracellular matrix abnormalities in schizophrenia

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