Behavioral and neuroinflammatory effects caused by a simulated poverty model in mice: implications for panic disorder

Abstract

Panic disorder (PD) is a chronic, disabling pathology, characterized by the recurrence of unexpected panic attacks. Recently, a model of neonatal stress in rodents was proposed, which consists of simulating a condition of poverty, limiting the material available for lactating dams to adequately care for their offspring. It has been shown that the limited bedding and nesting experience promotes changes in the behavior of the offspring, in addition to inducing neuroimmune alterations. Recently gathered evidence in our laboratory suggests that this stressor is also able to increase the adult animal's vulnerability to panic attack-evoking stimuli. In this context, the present study aims to evaluate the behavioral and neuroinflammatory effects caused by the limited bedding and nesting stress protocol in mice. For this, will be evaluated in the offspring of C57BL/6 mice, males and females, the behavioral consequences of exposure to a high concentration of CO2 (20%), a well-known panicogenic stimulus. In addition, we will evaluate the activation of microglia and astrocytes, as well as the levels of pro- and anti-inflammatory cytokines in the dorsal periaqueductal gray matter, dorsal raphe nucleus, medial hypothalamus and locus coeruleus, areas involved in the pathophysiology of PD. In the second and third stages of this project, the same behavioral and neuroinflammatory parameters will be evaluated after an early intervention or chronic treatment in adult life of animals with drugs that modulate glial cells, more specifically, minocycline and PLX5562. With this work, we expect to expand the knowledge about the environmental and neurobiological factors that predispose PD, in addition to better understanding the impacts of adversities suffered in childhood.