Environmental Enrichment Protects against Neurotoxic Effects of Lipopolysaccharide: A Comprehensive Overview

Abstract

Neuroinflammation is a pathophysiological condition associated with damage to the nervous system. Maternal immune activation and early immune activation have adverse effects on the development of the nervous system and cognitive functions. Neuroinflammation during adulthood leads to neurodegenerative diseases. Lipopolysaccharide (LPS) is used in preclinical research to mimic neurotoxic effects leading to systemic inflammation. Environmental enrichment (EE) has been reported to cause a wide range of beneficial changes in the brain. Based on the above, the purpose of the present review is to describe the effects of exposure to EE paradigms in counteracting LPS-induced neuroinflammation throughout the lifespan. Up to October 2022, a methodical search of studies in the literature, using the PubMed and Scopus databases, was performed, focusing on exposure to LPS, as an inflammatory mediator, and to EE paradigms in preclinical murine models. On the basis of the inclusion criteria, 22 articles were considered and analyzed in the present review. EE exerts sex- and age-dependent neuroprotective and therapeutic effects in animals exposed to the neurotoxic action of LPS. EE’s beneficial effects are present throughout the various ages of life. A healthy lifestyle and stimulating environments are essential to counteract the damages induced by neurotoxic exposure to LPS.

Mitochondrial antioxidant elamipretide improves learning and memory impairment induced by chronic sleep deprivation in mice

“…Progressive neuroinflammation plays a primary role in the cognitive impairment related with neurodegenerative diseases such as Alzheimer's disease and Huntington's disease (Bains et al., 2022; Decandia et al., 2023). Neuroinflammation influences cell proliferation and differentiation, synaptic plasticity, and cognitive function (Bai et al., 2023; Cangalaya et al., 2023).…”

Advance in Neurotoxicity Research from Development to Aging

“…Moreover, they describe such a link as the first example of a microbiome-derived neurotoxic glycolipid having significant detrimental miRNA-mediated actions on the expression of NF-L, a filamentous protein known to be important in the maintenance of neuronal and synaptic homeostasis. However, in relation to LPS neurotoxicity, two papers proposed in the present Special Issue describe the protective effects of two different kinds of non-pharmacological interventions, such as Environmental Enrichment (EE) [7] and dietary supplementation [6].…”

“…Landolfo and colleagues [7] focused their review on the beneficial effects of EE, defined as a combination of enhanced stimulations involving cognitive, social, and physical factors [57,58]. EE results in a wide range of brain changes, such as increased synaptogenesis, neurogenesis, glycogenesis, angiogenesis, and modulations of neurotrophic factors and neuroinflammation, inflammation, immune senescence, and DNA epigenetic modification, with the resulting modulation of cognition and behavior [59,60].…”

“…This Special Issue includes a total of eight papers addressing the effects of the exposure to different neurotoxic agents in both developmental and/or aging stages. Namely, advances on the specific aspects of the neurotoxicity of metals (such as zinc, silver, and iron [1][2][3]), inhalational anesthetics (such as sevoflurane [4]), bacterial endotoxins (such as Lipopolysaccharide (LPS) [5][6][7]), as well as Amyloid β (Aβ)-induced cytotoxicity [8] during different stages of development (from gestational and postnatal periods to adulthood and old age) are described in the present Special Issue and will be discussed as follows:…”