Extracellular matrix-glial abnormalities in the amygdala and entorhinal cortex of subjects diagnosed with schizophrenia.
BACKGROUND
Chondroitin sulfate proteoglycans (CSPGs), a main component of the brain extracellular matrix, regulate developmental and adult neural functions that are highly relevant to the pathogenesis of schizophrenia. Such functions, together with marked expression of CSPGs in astrocytes within the normal human amygdala and evidence of a disruption of astrocytic functions in this disease, point to involvement of CSPG-glial interactions in schizophrenia.


OBJECTIVE
Chondroitin sulfate proteoglycan-related abnormalities involve glial cells and extracellular matrix pericellular aggregates (perineuronal nets) in the amygdala and entorhinal cortex of subjects with schizophrenia.


METHODS
Postmortem case-control study.


METHODS
The Translational Neuroscience Laboratory at McLean Hospital, Harvard Medical School. Specimens were obtained from the Harvard Brain Tissue Resource Center at McLean Hospital.


METHODS
Two separate cohorts of healthy control (n = 15; n = 10) and schizophrenic (n = 11; n = 10) subjects and a cohort of subjects with bipolar disorder (n = 11).


METHODS
Quantitative, immunocytological, and histological postmortem investigations.


METHODS
Numerical densities of CSPG-positive glial cells and perineuronal nets, glial fibrillary acidic protein-positive astrocytes, and total numbers of parvalbumin-positive neurons in the deep amygdala nuclei and entorhinal cortex.


RESULTS
In schizophrenia, massive increases in CSPG-positive glial cells were detected in the deep amygdala nuclei (419%-1162%) and entorhinal cortex (layer II; 480%-1560%). Perineuronal nets were reduced in the lateral nucleus of the amygdala and lateral entorhinal cortex (layer II). Numerical densities of glial fibrillary acidic protein-positive glial cells and total numbers of parvalbumin-positive neurons were unaltered. Changes in CSPG-positive elements were negligible in subjects with bipolar disorder.


CONCLUSIONS
Marked changes in functionally relevant molecules in schizophrenia point to a pivotal role for extracellular matrix-glial interactions in the pathogenesis of this disease. Disruption of these interactions, unsuspected thus far, may represent a unifying factor contributing to disturbances of neuronal migration, synaptic connectivity, and GABAergic, glutamatergic, and dopaminergic neurotransmission in schizophrenia. The lack of CSPG abnormalities in bipolar disorder points to a distinctive aspect of the pathophysiology of schizophrenia in key medial temporal lobe regions.
Pantazopoulos
Harry
H
Translational Neuroscience Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
Woo
Tsung-Ung W
TU
Lim
Maribel P
MP
Lange
Nicholas
N
Berretta
Sabina
S
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000679:Amygdala / Q000378:metabolism* / Q000473:pathology; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001714:Bipolar Disorder / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D018728:Entorhinal Cortex / Q000378:metabolism* / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D012559:Schizophrenia / Q000453:epidemiology* / Q000378:metabolism* / Q000473:pathology; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
D011508:Chondroitin Sulfate Proteoglycans