Perineuronal Nets and their implications in neuropsychiatric illnesses

Perineuronal Nets (PNN’s) were first discovered at the end of the 19th century. A PNN is a specialized extracellular matrix (ECM) structure that surrounds specific cell types within the central nervous system. PNN’s serve a wide variety of functions, including protection, assisting normal function, providing anchor points for neurons and glial cells, aiding in neurotransmission, neurodevelopment, and neuroplasticity. Recently ECM has been incorporated as a functioning unit into the model of the standard synapse. The standard model of the synapse is now viewed as a “tetrapartite” synapse made of four parts: presynaptic neurons, postsynaptic neurons, glial cells, and the ECM. Each of these plays a key role in successful and correct neurotransmission. This paper will present a review of the research regarding the roll of PNN’s in three different neuropsychiatric diseases: Alzheimer’s, Schizophrenia, and Major Depressive Disorder (MDD). The dominating view of neuropsychiatric illnesses and treatments for the last several decades has been one of a two part synapse. With treatment focusing primarily on correcting the neurotransmitter imbalances seen in these diseases. Current research is challenging the understanding of how the basic synapse works, and the involvement of glial cells and the ECM in a variety of neurological diseases. Alterations in ECM function has been shown to be at least partially responsible for the pathology seen in the three diseases analyzed. This provides a novel approach to new treatments that do not rely on neurotransmitter replacement therapies and could possibly enable patients to receive better treatment in the future.