Decreased Density of Perineuronal Net in Prelimbic Cortex Is Linked to Depressive-Like Behavior in Young-Aged Rats.

Zhoulong Yu,Die Hu,Jie Shi,Lin Lu,Wen Zhang,Na Chen,Yi Yuan,Wenxi Chen,Shiqiu Meng,Ying Han

doi:10.3389/fnmol.2020.00004

Abstract

Perineuronal nets (PNNs) are condensed extracellular matrix (ECM) structures regulating developmental plasticity and protecting neurons against oxidative stress. PNN abnormalities have been observed in various psychiatric disorders such as schizophrenia and bipolar disorder, but the relationship between PNN density and depression still remains unclear. In the present study, we examined the density and components of PNNs including aggrecan, neurocan and Tenascin-R in the prelimbic cortex (PrL) after chronic unpredictable mild stress (CUMS). We found that depressive-like behaviors were induced after 30 days of CUMS accompanied by decreases in PNN+ cell density and aggrecan expression in the PrL. In addition, rats subjected to 20 days of CUMS were separated into vulnerable and resilient subpopulations that differ along several behavioral domains. Consistently, the density of PNNs and the expression level of neurocan in the vulnerable group were decreased compared to control and resilient groups. Finally, we examined individual differences based on locomotion in a novel context and classified rats as high responding (HR) and low responding (LR) phenotypes. The density of PNNs and the expression level of neurocan in the LR group were lower than the HR group. Moreover, the LR rats were more susceptible to depressive-like behaviors compared with HR rats. Altogether, these results suggest that the density of PNNs in the PrL is associated with depressive-like behaviors in young-aged rats, and it may serve as a potential endophenotype or therapeutic target for depression.

Highlights

Depression is a debilitating psychiatric disorder that causes disability and suicide worldwide (Moussavi et al, 2007; Phillips et al, 2009)
The expression of Perineuronal nets (PNNs) components, including aggrecan, neurocan and Tn-R in prelimbic cortex (PrL) were assessed by Western blot (n = 7 per group)
The expression of aggrecan (two-way analysis of variance (ANOVA), stress × time interaction, F(2,36) = 0.9925, p > 0.05, main effect of stress, F(1,36) = 11.99, p < 0.01; main effect of time, F(2,49) = 0.9308, p > 0.05; post hoc test, 30 days Control vs. 30 days chronic unpredictable mild stress (CUMS), p < 0.05; Figure 1F) is decreased after 30 days of CUMS, but chronic stress had no significant effects on the protein levels of neurocan and Tn-R in the PrL

Summary

Introduction

Depression is a debilitating psychiatric disorder that causes disability and suicide worldwide (Moussavi et al, 2007; Phillips et al, 2009). An individual’s response to stress is determined by both genetic and environmental elements and their complex interactions. Rodent models such as chronic unpredictable mild stress (CUMS) and social. A vast literature describes that the individual differences in response to stress or a novel environment contribute to explain differential susceptibility to develop abnormal behaviors and are important predictors for the occurrence of neuropsychiatric disorders including depression (Armario and Nadal, 2013; Carreira et al, 2017; Weger and Sandi, 2018), but the biological basis underlying the resilience to depression is still poorly understood. PNNs serve as a protective barrier and protect fast-spiking interneurons against oxidative stress and neurotoxins (Morawski et al, 2004, 2010, 2012; Cabungcal et al, 2013)

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Results

Conclusion