Child abuse associates with increased recruitment of perineuronal nets in the ventromedial prefrontal cortex: a possible implication of oligodendrocyte progenitor cells

Abstract

Child abuse (CA) is a strong predictor of psychopathologies and suicide, and can lastingly alter normal trajectories of brain development, particularly in areas closely linked to emotional responses such as the prefrontal cortex (PFC). Yet, the cellular underpinnings of these enduring effects are unclear. Childhood and adolescence are marked by the protracted formation of perineuronal nets (PNNs), which are essential in orchestrating the closure of developmental windows of cortical plasticity by regulating the functional integration of parvalbumin interneurons (PV) into neuronal circuits. Using well-characterized post-mortem brain samples, we explored the hypothesis that CA has lasting effects on the development of PNNs in the ventromedial PFC. We found that a history of CA was specifically associated with increased recruitment and maturation of PNNs. Through single-nucleus sequencing and fluorescent in-situ hybridization, we show that the expression of canonical components of PNNs is highly enriched in oligodendrocyte progenitor cells (OPCs), and that they are upregulated in CA victims. These findings suggest that early-life adversity may lead to persistent patterns of maladaptive behaviours by reducing the neuroplasticity of cortical circuits through the enhancement of developmental OPC-mediated PNN formation.

Effects of Early Life Stress on the Developing Basolateral Amygdala-Prefrontal Cortex Circuit: The Emerging Role of Local Inhibition and Perineuronal Nets

“…Along with the augmented density of PNNs, the authors observed an increase in intensity of the staining and coverage of enwrapped cells ( Figure 4 ) that was associated with child abuse. Using in situ hybridization, the same study found that 65% of vmPFC PV-positive cells were surrounded by PNNs in psychiatrically healthy controls ( Tanti et al, 2020 ) which is similar to the ratio calculated in rodent studies using IHC ( Van’t Spijker and Kwok, 2017 ). The ratio of neurons enwrapped by PNNs was disturbed in depressed suicides with a history of child abuse.…”

“…To our knowledge, a single study has examined the possible consequences of ELS on PNNs in human post-mortem tissue. This recent paper reported an increase in PNNs in layers III, IV, V, and VI of the vmPFC of adult depressed suicides with a history of severe child abuse ( Tanti et al, 2020 ). Along with the augmented density of PNNs, the authors observed an increase in intensity of the staining and coverage of enwrapped cells ( Figure 4 ) that was associated with child abuse.…”

“…Perineuronal nets (PNNs) are lattice-like structures consisting of large molecular aggregates composed primarily of chondroitin sulfate proteoglycans (neurocan, brevican, aggrecan, and versican) and extracellular matrix components such as collagen, laminin and fibronectin as well as additional molecules ( Tsien, 2013 ; Van’t Spijker and Kwok, 2017 ). Components of PNNs are thought to be contributed by both neurons and glial cells ( Carulli et al, 2006 ; Tanti et al, 2020 ) although their development is not yet fully understood. Evidence in animals suggest that PNNs may serve very different functions in specific brain regions, for example, loss of PNNs in the adult mouse visual cortex enhances LTP formation ( de Vivo et al, 2013 ) whereas similar manipulations in the adult mouse LA reduces LTP ( Gogolla et al, 2009 ).…”

Parvalbumin interneuron alterations in stress-related mood disorders: A systematic review

“…PNNs are established during postnatal development and their maturation is intimately associated with the opening and closure of critical periods of enhanced neuroplasticity ( Wen et al., 2018 ). Recent evidence suggests that PNNs on PV neurons may be altered by early life stress in animals ( Gildawie et al., 2019 ; Mukhopadhyay et al., 2021 ) and humans ( Tanti et al., 2020 ), which are thought to reflect changes in PV cell excitability, plasticity, oxidative stress, and other metabolic functions ( Wen et al., 2018 ). PNNs are typically labeled using a lectin called Wisteria floribunda lectin (WFL) or agglutinin (WFA), which binds a carbohydrate residue found in PNNs, in particular those surrounding PV neurons.…”

Molecular impacts of childhood abuse on the human brain

“…Moreover, perineuronal nets (PNNs) have heightened affinity to PV-expressing GABAergic interneurons, and PNN formation and condensation is thought to coincide with the closure of critical periods ( Reichelt et al, 2019 ). New evidence suggests that CA might be associated with increased recruitment and maturation of PNNs in human ventromedial prefrontal cortex as well as with upregulated expression of canonical components of PNNs in oligodendrocyte progenitor cells ( Tanti et al, 2020 ). Despite these findings, it has been demonstrated that PNNs may also be dynamically regulated in adulthood, in processes such as learning and memory formation ( Banerjee et al, 2017 ; Carulli et al, 2020 ).…”