Blocking PirB Function Increases Dendritic Spine Density in the Prefrontal Cortex of Adult Rats
Abstract
Schizophrenia is a psychotic disorder consisting of positive, negative, and cognitive symptoms. While patients currently have access to treatments for the positive and negative symptoms, no satisfactory treatment exists to alleviate the cognitive deficits, which cause severe impairments to the quality of life of patients and their families. Although the mechanisms underlying the cognitive deficits of schizophrenia are not clear, a decreased dendritic spine density on layer 3 pyramidal neurons in the dorsolateral prefrontal cortex has been strongly implicated. Generally, the adult brain is not permissive to the formation of new dendritic spines. Recently, an immune receptor called paired immunoglobulin-like receptor B (PirB) has been identified to play an active role in inhibiting dendritic spine growth in the adult brain. The current thesis infused PirB blocker into the prefrontal cortex of a rat model that recapitulates several neuroanatomical changes and behavioral deficits associated with schizophrenia, and then analyzed dendritic spine densities using Golgi-Cox method and immunohistochemical labelling of Neurabin-2. The results showed a significant increase in spine density in Golgi-Cox impregnated neurons, and increased Neurabin-2 labelling following infusions of PirB blocker compared to vehicle infusions. These results provide a promising first step in the development of a novel treatment for the cognitive deficits of schizophrenia.