Reopening the sensitive period of susceptibility to stress through perineuronal nets degradation

• Grant number: 21/03391-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2021
• End date: October 31, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Felipe Villela Gomes
• Grantee: Debora Akemi Endo Colodete
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 18/17597-3 - The impact of stress on the dopamine system depends on the state of the critical period of neuroplasticity: implications for depression and schizophrenia and for the study of new drug targets, AP.JP
• Associated scholarship(s): 22/06330-1 - The impact of stress in mice lacking molecular breaks of critical periods of plasticity, BE.EP.MS

Abstract

The onset of some psychiatric disorders, such as schizophrenia, anxiety disorders, and depression, often occurs in late adolescence and/or early adulthood, which is a period of greater vulnerability to socioenvironmental factors. The causes of these disorders are still unclear. However, evidence suggests that socioenvironmental factors, such as trauma, psychosocial stress, urbanicity, physical and/or sexual abuse, along with genetic predisposition, may increase the individual's susceptibility to developing psychiatric disorders. The impact of these factors seems to be more pronounced during sensitive periods of development, such as childhood and adolescence, when parvalbumin-positive (PV) interneurons have not reached their "mature" state. It is thought that stress during these periods causes functional loss of PV interneurons in the ventral hippocampus (vHip) and prefrontal cortex. These interneurons modulate the activity of pyramidal neurons contributing to the excitatory-inhibitory balance, which is impaired in some psychiatric disorders. The period of vulnerability of PV interneurons occurs until the end of the critical period of development, which is completed with the appearance of the perineuronal nets (PNNs) around these interneurons. PNNs involve and protect PV interneurons from oxidative and metabolic damage. Therefore, during adolescence, when the PNNs are not yet fully formed, stress can damage PV interneurons. If this hypothesis is correct, it could be predicted that reopening the sensitive period in adulthood may recreate an adolescent-like phenotype of susceptibility to stress. It is suggested that the degradation of PNNs allows the reopening of the sensitive period in the adult brain. Thus, this project aims to investigate whether the degradation of PNNs in the vHip of adult animals through the local infusion of the enzyme chondroitinase ABC would increase the impact of stress on PV interneurons, reinforcing the idea that they are more susceptible in periods of higher plasticity.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

COLODETE, Debora Akemi Endo. Reopening the sensitive period of susceptibility to stress through perineuronal nets degradation. 2023. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.