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The brain extracellular matrix (ECM) has garnered increasing attention as a fundamental component of brain function in a predominantly "neuron-centric" paradigm. Particularly, the perineuronal nets (PNNs), a specialized net-like structure formed by ECM aggregates, play significant roles in brain development and physiology. PNNs enwrap synaptic junctions in various brain regions, precisely balancing new synaptic formation and long-term stabilization, and are highly dynamic entities that change in response to environmental stimuli, especially during the neurodevelopmental period. They are found mainly surrounding parvalbumin (PV)-expressing GABAergic interneurons, being proposed to promote PV interneuron maturation and protect them against oxidative stress and neurotoxic agents. This structural and functional proximity underscores the crucial role of PNNs in modulating PV interneuron function, which is critical for the excitatory/inhibitory balance and, consequently, higher-level behaviours. This review delves into the molecular underpinnings governing PNNs formation and degradation, elucidating their functional interactions with PV interneurons. In the broader physiological context and brain-related disorders, we also explore their intricate relationship with other molecules, such as reactive oxygen species and metalloproteinases, as well as glial cells. Additionally, we discuss potential therapeutic strategies for modulating PNNs in brain disorders., (© 2024 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)

Background and Hypothesis: Redox dysregulation has been proposed as a convergent point of childhood trauma and the emergence of psychiatric disorders, such as schizophrenia (SCZ). A critical region particularly vulnerable to environmental insults during adolescence is the ventral hippocampus (vHip). However, the impact of severe stress on vHip redox states and their functional consequences, including behavioral and electrophysiological changes related to SCZ, are not entirely understood., Study Design: After exposing adolescent animals to physical stress (postnatal day, PND31-40), we explored social and cognitive behaviors (PND47-49), the basal activity of pyramidal glutamate neurons, the number of parvalbumin (PV) interneurons, and the transcriptomic signature of the vHip (PND51). We also evaluated the impact of stress on the redox system, including mitochondrial respiratory function, reactive oxygen species (ROS) production, and glutathione (GSH) levels in the vHip and serum., Study Results: Adolescent-stressed animals exhibited loss of sociability, cognitive impairment, and vHip excitatory/inhibitory (E/I) imbalance. Genome-wide transcriptional profiling unveiled the impact of stress on redox system- and synaptic-related genes. Stress impacted mitochondrial respiratory function and changes in ROS levels in the vHip. GSH and glutathione disulfide (GSSG) levels were elevated in the serum of stressed animals, while GSSG was also increased in the vHip and negatively correlated with sociability. Additionally, PV interneuron deficits in the vHip caused by adolescent stress were associated with oxidative stress., Conclusions: Our results highlight the negative impact of adolescent stress on vHip redox regulation and mitochondrial function, which are partially associated with E/I imbalance and behavioral abnormalities related to SCZ., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Adolescent individuals exhibit great variability in cortical dynamics and behavioral outcomes. The developing adolescent brain is highly sensitive to social experiences and environmental insults, influencing how personality traits emerge. A distinct pattern of mitochondrial gene expression in the prefrontal cortex (PFC) during adolescence underscores the essential role of mitochondria in brain maturation and the development of mental illnesses. Mitochondrial features in certain brain regions account for behavioral differences in adulthood. However, it remains unclear whether distinct adolescent behavioral phenotypes and the behavioral consequences of early adolescent stress exposure in rats are accompanied by changes in PFC mitochondria-related genes and mitochondria respiratory chain capacity. We performed a behavioral characterization during late adolescence (postnatal day, PND 47-50), including naïve animals and a group exposed to stress from PND 31-40 (10 days of footshock and 3 restraint sessions) by z-normalized data from three behavioral domains: anxiety (light-dark box tests), sociability (social interaction test) and cognition (novel-object recognition test). Employing principal component analysis, we identified three clusters: naïve with higher-behavioral z-score (HBZ), naïve with lower-behavioral z-score (LBZ), and stressed animals. Genome-wide transcriptional profiling unveiled differences in the expression of mitochondria-related genes in both naïve LBZ and stressed animals compared to naïve HBZ. Genes encoding subunits of oxidative phosphorylation complexes were significantly down-regulated in both naïve LBZ and stressed animals and positively correlated with behavioral z-score of phenotypes. Our network topology analysis of mitochondria-associated genes found Ndufa10 and Cox6a1 genes as central identifiers for naïve LBZ and stressed animals, respectively. Through high-resolution respirometry analysis, we found that both naïve LBZ and stressed animals exhibited a reduced prefrontal phosphorylation capacity and redox dysregulation. Our findings identify an association between mitochondrial features and distinct adolescent behavioral phenotypes while also underscoring the detrimental functional consequences of adolescent stress on the PFC., (© 2023. The Author(s).)

Despite the standard approaches to treat the highly aggressive and invasive glioblastoma (GBM), it remains incurable. In this sense, cannabinoids highlight as a promising tool, because this tumor overexpresses CB1 and/or CB2 receptors and being, therefore, can be susceptible to cannabinoids treatment. Thus, this work investigated the action of the cannabinoid agonist WIN55-212-2 on GBM cell lines and non-malignant cell lines, in vitro and in vivo. WIN was selectively cytotoxic to GBM cells. These presented blebbing and nuclear alterations in addition to cell shrinkage and chromatin condensation. WIN also significantly inhibited the migration of GAMG and U251 cells. Finally, the data also showed that the antitumor effects of WIN are exerted, at least to some extent, by the expression of p53 and increased cathepsin D in addition to the decreased expression of HSP70.This data can indicate caspase-independent cell death mechanism. In addition, WIN decreased tumoral perimeter as well as caused a reduction the blood vessels in this area, without causing lysis, hemorrhage or blood clotting. So, the findings herein presented reinforce the usefulness of cannabinoids as a candidate for further evaluation in treatment in glioblastoma treatment., (Copyright © 2019 Elsevier Ltd. All rights reserved.)