Plasticidade aumentada no córtex pré-frontal de ratos com a remoção de redes perineuronais

Abstract

Aging is associated with decreasing brain plasticity, especially after the closure of the critical periods of plasticity (a sensitive limited period in life of elevated brain plasticity). Some brain regions may be particularly affected by aging, such as prefrontal cortex (PFC), which has a key role in the organization of higherorder cognitive aspects, the executive functions, including attention, set-shifting, working memory, decision making, etc. Decline of plasticity in the PFC and the brain is attributed mainly to the appearance of a structure called perineuronal net (PNNs) which enwraps the cell body and dendrites of many classes of neurons. PNNs are extracellular matrix structures consisting of chondroitin sulfate proteoglycans, hyaluronan, link proteins and tenascin, and are involved in the control of experience-dependent cortical plasticity and the closure of critical periods. Degradation of PNNs with the enzyme Chondroitinase ABC (ChABC) restores juvenile forms of plasticity in the adult brain. Here, we examined the developmental time course of PNN formation in the medial PFC (mPFC) of male rats ranging in age from the seventh postnatal day (PND) to 11 months. We used the lectin Vicia villosa agglutinin that binds to glycosaminoglycan chains present in the PNNs. We also investigated whether the digestion of PNNs by bilateral injection of ChABC in the mPFC may open a new window of increased plasticity in adult rats, evaluated by two executive function tests: object recognition and spontaneous alternation. We found that immature PNNs were observed in PND 20 animals, but mature PNNs were seen only after PND 75-90 and a mature form appeared around 5 months of age. In addition, our results showed that enzymatic PNN removal promoted a significant increase in performance in the ChABC-treated animals in both behavioral tests. The present study reveals for the first time the temporal development of PNN formation in the rat mPFC. We also show that the degradation of PNNs with ChABC not only promotes plasticity but also potentiates cognitive abilities in adult animals.