Aggrecan expression, a component of the inhibitory interneuron perineuronal net, is altered following an early-life seizure

Abstract

The perineuronal net (PN), a component of the neural extracellular matrix (ECM), is a dynamic structure whose expression decreases following diminished physiological activity. Here, we analyzed the effects of increased neuronal activity on the development of aggrecan, a component of the PN, in the hippocampus. We show aggrecan expression to be prominent around parvalbumin (PV) interneurons in the postnatal hippocampus. Moreover, after seizure induction in early life there was a significant increase in aggrecan expression in a region specific manner during the course of development. We conclude that increased neuronal activity leads to accelerated expression of PNs in the hippocampus that attenuates in the adult hippocampus. This study shows the dynamic nature of the PN component of the ECM and the role neuronal activity has in molding the extracellular milieu of inhibitory interneurons.

Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia

“…For example, increased PV and WFA labeling during the closure of critical periods in sensory cortices is likely driven by increased excitatory input (McRae and Porter, 2012). In addition, both aggrecan expression (McRae et al, 2010) and glycosylation state (Lander et al, 1997) are activity-dependent. Because DLPFC layer 3 PCs appear to receive fewer excitatory synaptic inputs (Glantz and Lewis, 2000) resulting in a lower expression of gene products critical for energy production (Arion et al, 2015), their lower activity would result in less excitatory drive to neighboring layer 3 PV cells (which receive a large proportion of their excitatory inputs from layer 3 PCs (Melchitzky et al, 1998).…”

The perineuronal net component of the extracellular matrix in plasticity and epilepsy

“…The appearance of the PN in cortex, spinal cord, and hippocampus is relatively late during postnatal development and not likely involved in early developmental processes such as cell migration, synaptogenesis or process elongation (Hockfiled and McKay, 1983; Sur et al, 1988; Kalb and Hockfield, 1988; Lurie et al, 1997; Balmer et al, 2009; McRae et al, 2010). It is of interest that PNs first appear around the close of the critical period for multiple cortical areas.…”

“…While all CSPGs family members can be found in PNs, aggrecan is unique because, unlike the other CSPGs and lecticans, in the CNS it is found exclusively in the PNs (Matthews et al, 2002; Galtrey et al, 2008; Morawski et al, 2012). Aggrecan expressing PNs develop postnatally in the hippocampus primarily around PV interneurons (McRae et al, 2010, 2012). Inducing SE with kainic acid early in development, prior to the expression of the PN led to accelerated expression of aggrecan positive PNs.…”

Regulation of astrocyte glutamine synthetase in epilepsy

“…Thirdly, loss of the extracellular matrix component aggrecan leads to differentiation of astrocytes with induction of GS, GFAP and the glutamate transporter GLAST (Domowicz et al, 2008). Aggrecan accumulates in the brain in response to early-life seizures and therefore may prevent astrocytes from differentiating into a GS-expressing phenotype (McRae et al, 2010). Finally, studies in peripheral organs have shown that the GLUL gene is induced by beta-catenin, a cytoplasmic protein involved in the Wnt pathway (Audard et al, 2008; Cadoret et al, 2002; Kruithof-de Julio et al, 2005).…”