Toxoplasma gondii infection damages the perineuronal nets in a murine model

BACKGROUND Behavioral and neurochemical alterations associated with toxoplasmosis may be influenced by the persistence of tissue cysts and activation of an immune response in the brain of Toxoplasma gondii-infected hosts. The cerebral extracellular matrix is organised as perineuronal nets (PNNs) that are both released and ensheath by some neurons and glial cells. There is evidences to suggest that PNNs impairment is a pathophysiological mechanism associated with neuropsychiatric conditions. However, there is a lack of information regarding the impact of parasitic infections on the PNNs integrity and how this could affect the host's behavior. OBJECTIVES In this context, we aimed to analyse the impact of T. gondii infection on cyst burden, PNNs integrity, and possible effects in the locomotor activity of chronically infected mice. METHODS We infected mice with T. gondii ME-49 strain. After thirty days, we assessed locomotor performance of animals using the open field test, followed by evaluation of cysts burden and PNNs integrity in four brain regions (primary and secondary motor cortices, prefrontal and somesthetic cortex) to assess the PNNs integrity using Wisteria floribunda agglutinin (WFA) labeling by immunohistochemical analyses. FINDINGS AND MAIN CONCLUSIONS Our findings revealed a random distribution of cysts in the brain, the disruption of PNNs surrounding neurons in four areas of the cerebral cortex and hyperlocomotor behavior in T. gondii-infected mice. These results can contribute to elucidate the link toxoplasmosis with the establishment of neuroinflammatory response in neuropsychiatric disorders and to raise a discussion about the mechanisms related to changes in brain connectivity, with possible behavioral repercussions during chronic T. gondii infection.

Perineuronal nets-a double-edged sword regulating neuropsychiatric disorders / 中国药理学通报

Perineuronal nets (PNNs) are unique extracellular matrix (ECM) structures surrounding parvalbumin (PV) positive intemeurons in the central nervous system (CNS). The intact structure of PNNs is critical to the function of CNS. PNNs regulate the function of GABA neurons, inhibit the damage of neurons induced by reactive oxygen species, and also participate in the regulation of neuroplasticity and the development of central nervous system. They will change in quantity and quality after mental disorders, aging, memory and drug abuse. Here the focus is on how the PNNs protect interneuron and control plasticity , and on the role of PNNs in memory in normal aging, Alzheimer's disease and drug addiction, and the association with altered PNNs formation. Understanding the molecular mechanism on PNNs would offer insights into new treatments of relevant diseases.

Enriched environment contributes to recovery of visual acuity and increases perineuronal nets in monocular-deprived animals

The aim of the present study was to analyze the influence of enriched environment on the distribution of perineuronal nets (PNNs) using a stereogically based unbiased protocol and visual acuity in adult Swiss albino mice that underwent monocular deprivation during the critical period of postnatal development. Eight female Swiss albino mice were monocular deprived on postnatal day 10 and divided into two groups at weaning: standard environment (SE group, n = 4) and enriched environment (EE group, n = 4). After 3 months, all of the mice were subjected to grating visual acuity tests, sacrificed, and perfused with aldehyde fixative. The brains were removed and cut at 70 µm thickness in a vibratome and processed for lectin histochemical staining with Wisteria floribunda agglutinin (WFA). Architectonic limits of area 17 were conspicuously defined by WFA histochemical staining, and the optical fractionator stereological method was applied to estimate the total number of PNNs in the supragranular, granular, and infragranular layers. All groups were compared using Student's t-test at a 95 percent confidence level. Comparative analysis of the average PNN estimations revealed that the EE group had higher PNNs in the supragranular layer (2726.33 ± 405.416, mean ± standard deviation) compared with the SE group (1543.535 ± 260.686; Student's t-test, p = .0495). No differences were found in the other layers. Visual acuity was significantly lower in the SE group (0.55 cycles/degree) than in the EE group (1.06 cycles/degree). Our results suggest that the integrity of the specialized extracellular matrix PNNs of the supragranular layer may be essential for normal visual acuity development.