The impact of early life maternal deprivation on the perineuronal nets in the prefrontal cortex and hippocampus of young adult rats

Abstract

Early life stress negatively impacts brain development and affects structure and function of parvalbumin immunopositive (PV+) inhibitory neurons. Main regulators of PV+ interneurons activity and plasticity are perineuronal nets (PNNs), an extracellular matrix formation that enwraps PV+ interneurons mainly in the neocortex and hippocampus. To experimentally address the impact of early life stress on the PNNs and PV+ interneurons in the medial prefrontal cortex and dorsal hippocampus in rats, we employed a 24 h maternal deprivation protocol. We show that maternal deprivation in the medial prefrontal cortex of adult rats caused a decrease in density of overall PNNs and PNNs that enwrap PV+ interneurons in the rostral cingulate cortex. Furthermore, a staining intensity decrease of overall PNNs and PNN+/PV+ cells was found in the prelimbic cortex. Finally, a decrease in both intensity and density of overall PNNs and PNNs surrounding PV+ cells was observed in the infralimbic cortex, together with increase in the intensity of VGAT inhibitory puncta. Surprisingly, maternal deprivation did not cause any changes in the density of PV+ interneurons in the mPFC, neither had it affected PNNs and PV+ interneurons in the hippocampus. Taken together, our findings indicate that PNNs, specifically the ones enwrapping PV+ interneurons in the medial prefrontal cortex, are affected by early life stress.

Inhibitory, But Not Excitatory Synapses Are Reduced in the Hippocampus of the Six-Month-Old Alzheimer’s Disease Model Mouse

“…The loss of parvalbumin-positive interneurons was reported in the olfactory cortex of a similar APP/PS1 double transgenic mouse model ( 16) and electrophysiological deficits in PV-positive cortical interneurons were found (17). Additionally, selective vulnerability of PVpositive interneurons has been documented under different experimental conditions, including epilepsy (18), global ischemia (19), IL6 overexpression (20) and schizophrenia (21,22). In our study there were no indication of the loss of parvalbumin-positive interneurons in the hippocampus, based on the immunostaining pattern, thus it is rather the loss of axons and/or synaptic terminals that occurs in APPPS1 mice.…”

The long-term effects of maternal deprivation on the number and size of inhibitory interneurons in the rat amygdala and nucleus accumbens

“…Like in our study, they showed that GABAergic and extracellular maturation corresponds with major changes in neurocircuitry and plasticity. New evidence showing that early life stress alters perineuronal nets that play important role stabilizing synaptic inputs to developing inhibitory interneurons ( Guadagno et al, 2021 ; Jakovljević et al, 2022 ). Maternal deprivation, as a model of early life stress, also affects the physiology of the nucleus accumbens.…”

“…In all these structures, structure volume, number of principal neurons as well as interneurons were decreased ( Aksić et al, 2014 , 2021 ), and the evidence for the increased oxidative stress were found ( Marković et al, 2017 ). Additionally, the number and structure of perineuronal nets around PV+, as well as PV-neurons were altered in the lymbic cortex, but not in the hippocampus ( Jakovljević et al, 2022 ). These findings are accompanied by reduced cholinergic input to those structures, as well as overall loss of dopaminergic neurons in the substantia nigra and ventral tegmental area ( Marković et al, 2014 ; Kapor et al, 2020 ).…”

“…In order to visualize brain structures, every 10th microscope slide (containing 4 sections at 250-μm distance from each other), was stained using standard cresyl-violet staining protocol, as previously described ( Jakovljević et al, 2022 ). Briefly, the sections were rinsed for 3 min in 2 changes of xylene, 95, and 70% ethanol and distilled water.…”

The Role of Tenascin-C on the Structural Plasticity of Perineuronal Nets and Synaptic Expression in the Hippocampus of Male Mice

“…PNNs have been reported to be altered in conditions such as early life stress [23], schizophrenia [24], Alzheimer's disease (AD) [25], ischemia [26,27], and Rett syndrome [28]. In fact, the dysfunction or disruption of PNNs in the hippocampus has been associated with the modulation of memory [29], highlighting their essential role in higher cognitive functions.…”