Extracellular matrix remodeling with stress and depression: Studies in human, rodent and zebrafish models

Abstract

Emerging evidence suggests that extracellular matrix (ECM) alterations occur with stress. Specifically, increases in perineuronal net (PNN) deposition have been observed in rodents exposed to chronic corticosterone or persistent social defeat stress. The PNN is a specific form of ECM that is predominantly localized to parvalbumin (PV)-expressing inhibitory interneurons where it modulates neuronal excitability and brain oscillations that are influenced by the same. Consistent with a role for ECM changes in contributing to the depressive phenotype, recent studies have demonstrated that monoamine reuptake inhibitor type antidepressants can reduce PNN deposition, improve behavior and stimulate changes in gamma oscillatory power that may be important to mood and memory. The present review will highlight studies in humans, rodents and zebrafish that have examined stress, PNN deposition and/or gamma oscillations with a focus on potential cellular and molecular underpinnings.

Keywords: depression; gamma oscillations; matrix metalloproteinase; perineuronal net; zebrafish.

Figure 1.

To date, studies of stress and changes in PNN deposition or neuronal population dynamics have been performed in rodents (Khalid et al., 2016; Riga et al., 2017). Stress (middle panel) has been linked to increased PNN deposition (Riga et al., 2017) and reduced complexity of pyramidal dendrites, which in turn may reduce E/I balance to diminish the power of gamma oscillations (Khalid et al., 2016). PNN changes may also influence the abundance of SWRs (Sun et al., 2018). Antidepressant therapy (lower-most panel) may attenuate stress-related PNN deposition through its ability to increase MMP-9 levels (Tamasi et al., 2014; Alaiyed et al., 2019a), restore E/I balance, and normalize gamma power (Alaiyed et al., 2019a; Alaiyed et al., 2020).

Figure 2.

SWR events recorded from the anterodorsal lobe of a 35 day old wild-type (Ekkwill strain) zebrafish following tricaine anaesthesia, decapitation, brain extraction and 2h recovery as described (Vargas et al., 2012). A Traces shown are consecutive local field potential (LFP) recordings. SWR events with low amplitude (red arrowheads) and high amplitude (blue arrowheads) occur spontaneously. B. One large SWR event (marked by a broken line box in A) is displayed with an expanded scale. Top trace: filtered between 0.1–200 Hz, Bottom trace, filtered between 20–200Hz to show gamma and ripple oscillations. C. Power spectrum of the SWR event (black line). In red we show the power spectrum of background noise, 1 second following the SWR event. During the SWR, power peaks in low gamma (20–39), high gamma (50–100), and ripples (120Hz) can be seen in black, with signal above that of background noise.