title: Developmental pattern of perineuronal nets in the human prefrontal cortex and their deficit in schizophrenia.
abstract: 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
  The densities of PNNs were decreased by 70%-76% in layers 3 and 5 of the PFC in schizophrenia, compared with the normal control subjects, 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. That the timing of PNN development overlaps with the period when schizophrenia symptomatology gradually emerges raises the possibility that aberrant PNN formation might contribute to the onset of illness. Thus, characterization of the molecular mechanisms underlying PNN deficit might have important implications for the conceptualization of novel strategies for the diagnosis, treatment, early intervention, and prevention of schizophrenia.
authors.affiliation: Laboratory of Cellular Neuropathology, McLean Hospital, Belmont, MA 02478, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Mauney
authors.forename: Katina M
authors.initials: KM
authors.lastname: Athanas
authors.forename: Harry
authors.initials: H
authors.lastname: Pantazopoulos
authors.forename: Noel
authors.initials: N
authors.lastname: Shaskan
authors.forename: Eleonora
authors.initials: E
authors.lastname: Passeri
authors.forename: Sabina
authors.initials: S
authors.lastname: Berretta
authors.forename: Tsung-Ung W
authors.initials: TU
authors.lastname: Woo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001714:Bipolar Disorder / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005109:Extracellular Matrix / Q000473:pathology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000254:growth & development / Q000473:pathology*; D017397:Prefrontal Cortex / Q000254:growth & development / Q000473:pathology*; D012559:Schizophrenia / Q000473:pathology*; D055815:Young Adult
keywords: Bipolar disorder; GABA; cerebral cortex; development; schizophrenia; synaptic pruning