Extracellular Matrix Abnormalities in the Amygdala of Subjects with Schizophrenia

Abstract

Schizophrenia is a chronic, progressive disease distinguished by bizarre thinking, emotional disturbances, difficulties in motivation, and social dysfunction. Consistent findings have linked the GABAergic neurotransmitter system and the mechanisms regulating neuronal migration, synaptic formation, and neuroplasticity to schizophrenia pathophysiology. Recent evidence has also implicated a previously unsuspected factor, the brain extracellular matrix, in pathophysiology. Perineuronal nets (PNNs) are aggregates of brain extracellular matrix molecules, which form mesh-like structures around distinct classes of GABAergic neurons during late postnatal maturation. PNNs are known to control neuroplasticity, stabilize synaptic connections, regulate receptor trafficking, and protect neurons from oxidative stress. Abnormalities in PNN formation in the amygdala of schizophrenia subjects have previously been reported. The present study focused on PNN formation within the central nucleus of the amygdala (CE), as this had not been previously examined. The CE is an area known to be involved in the expression of fear responses and the generation of social behavior. Results showed no change in either the total number or the numerical density of PNNs in the CE in either subjects with schizophrenia or bipolar disorder, suggesting the resiliency of PNNs in this nucleus. Our study also revealed the presence of two distinct types of PNNs in the CE, whose morphology suggest they surround sub-types of GABAergic neurons expressing selected neuropeptides. Alterations in PNN formation seen within distinct amygdaloid nuclei offers clues into the neurobiological underpinnings of schizophrenia pathophysiology.