Neuroinflammation plays a critical role in the pathogenesis of most neurological and neurodegenerative diseases and therefore represents a potential therapeutic target. In this regard, accelerating the resolution process in chronic neuroinflammation may be an effective strategy to deal with the cognitive consequences of neuropathology and generalized inflammatory processes. N-acylethanolamine (NAE) derivatives of fatty acids, being highly active lipid mediators, possess pro-resolving activity in inflammatory processes and are promising agents for the suppression of neuroinflammation and its consequences. This paper is devoted to a study of the effects played by dietary supplement (DS), containing a composition of fatty acid-derived NAEs, obtained from squid Berryteuthis magister, on the hippocampal neuroinflammatory and memory processes. By detecting the production of pro-inflammatory cytokines and glial markers, a pronounced anti-inflammatory activity of DS was demonstrated both in vitro and in vivo. DS administration reversed the LPS-induced reduction in hippocampal neurogenesis and memory deterioration. LC-MS analysis revealed an increase in the production of a range of NAEs with well-documented anti-inflammatory activity in response to the administered lipid composition. To conclude, we found that tested DS suppresses the neuroinflammatory response by reducing glial activation, positively regulates neural progenitor proliferation, and attenuates hippocampal-dependent memory impairment.

Neuropathic pain is a persistent and exhausting condition which results from damage to the nervous system and is often accompanied by emotional and cognitive impairments. In this study, we investigated dynamic changes in pain-related behaviors over 8 weeks using a spared nerve injury (SNI) model in male C57Bl/6 mice. We examined behavioral outcomes in conjunction with glial activation, neurogenesis, and glutamatergic signaling in the hippocampus to elucidate the mechanisms underlying cognitive and affective alterations associated with chronic pain. Our findings demonstrate that SNI-induced neuropathic pain progressively increases anxiety-like behavior and impairs both working and long-term memory. These behavioral deficits are accompanied by significant activation of microglia and astrocytes, a reduction in hippocampal neurogenesis, and a decrease in the expression of NMDA and AMPA glutamate receptor subunits and the scaffolding protein PSD-95. Taken together, our results suggest that hippocampal neuroinflammation and associated synaptic dysfunction contribute to the affective and cognitive disturbances observed in chronic pain, providing insight into potential molecular targets for therapeutic intervention.

Background: Metabolic effects of oleoylethanolamide-based dietary supplement (OEA-DS) were studied in a model of dietary-induced obesity in mice. Obesity was induced by a 2-month high-fat, high-cholesterol diet, resulting in significant morphological changes in liver tissues and elevated cholesterol levels in the animals’ blood serum. Elevated levels of proinflammatory cytokines, oxidative stress, and hepatocyte apoptosis were also observed in the liver tissue. The aim of this study was to examine the mechanisms through which an OEA-based dietary supplement (OEA-DS) exerts a comprehensive influence on multiple aspects of the pathogenesis of MASLD, thereby demonstrating a robust hepatoprotective effect. Methods: mice were fed a high-fat, high-cholesterol diet with or without OEA-DS supplementation. Liver tissues and blood serum were analyzed for cholesterol levels, inflammatory markers (CD68, Iba-1, CD163, IL-1β, IL-6, TNFα), apoptotic markers (Bad, Bax, Bcl-2), nuclear receptors (PPAR-α, PPAR-γ, AdipoR1), and enzymes involved in lipolysis (Acox1, Cpt1a) and cholesterol metabolism (Ldlr, Furin, Pcsk9). Immunohistochemistry, Western blotting, and RT-PCR were used to assess protein expression and gene transcription. Results: administration of OEA-DS normalized cholesterol levels, decreased expression of inflammatory markers (CD68 and Iba-1), pro-apoptotic markers (Bad, Bax) and levels of pro-inflammatory cytokines (IL-1β, IL-6, TNFα). In parallel, the expression of nuclear receptors PPAR-α and PPAR-γ, adiponectin receptor 1 (AdipoR1), and anti-inflammatory (CD163) and anti-apoptotic (Bcl-2) markers have risen. OEA-DS administration induced the expression of liver lipolysis enzymes (Acox1, Cpt1a) and cholesterol metabolism factors (Ldlr, Furin), while simultaneously reducing the transcription of the proatherogenic factor Pcsk9. Conclusions: The results of this study suggest a complex action of OEA-DS in obesity-associated liver damage, which includes reduction of systemic inflammation.

Mild traumatic brain injury (mTBI) disrupts hippocampal network function through coordinated alterations in glial reactivity, synaptic integrity, and adult neurogenesis. Effective therapeutic approaches targeting these interconnected processes remain limited. Lipid-derived molecules capable of modulating these mTBI-induced disturbances are emerging as promising neuroprotective candidates. Here, we investigated the effects of N-stearidonylethanolamine (SDEA), an ω-3 ethanolamide, in a mouse model of mTBI. SDEA treatment attenuated astrocytic reactivity, restored Arc expression, and improved dendritic spine density and morphology in the CA1 hippocampal area. In the dentate gyrus, mTBI reduced Ki-67-indexed proliferation while leaving DCX-positive immature neurons unchanged, and SDEA partially rescued proliferative activity. These effects were accompanied by improvements in anxiety-like behavior and working-memory performance. Together, these findings demonstrate that SDEA modulates several key components of the glia-synapse-neurogenesis axis and supports functional recovery of hippocampal circuits following mTBI. These results suggest that ω-3 ethanolamides may represent promising candidates for multi-target therapeutic strategies in mTBI.

Background/Objectives: Mild traumatic brain injury (mTBI) can cause persistent neuroinflammation and astroglial reactivity. This study examined whether peri-injury administration of stearidonic acid ethanolamide (SDEA) was associated with changes in astrocyte-associated responses after mTBI and in primary astroglial cultures. Methods: Male C57BL/6 mice received SDEA (10 mg/kg, subcutaneously) for 2 days before mTBI, immediately after injury, and for 7 days thereafter. At 11 weeks post-injury, cortical GFAP immunoreactivity and the expression of astrocyte-associated markers, PPAR isoforms, and neurotrophic factors were assessed by immunohistochemistry and RT-qPCR. Primary astroglial cultures were treated with 1 or 10 μM SDEA for 48 h. Results: SDEA attenuated mTBI-associated increases in GFAP-positive cells and cortical Gfap and C3 expression while increasing S100a10 and Clcf1 expression. SDEA treatment was accompanied by increased cortical Ppara and Pparg mRNA expression and changes in the expression of neurotrophic-factor genes. In cultured astroglia, SDEA increased S100a10, Clcf1, Ppara, Pparg, Bdnf, Ngf, and Gdnf mRNA expression without significantly altering Gfap or C3. Conclusions: Peri-injury SDEA administration was associated with reduced chronic cortical GFAP reactivity and changes in selected astrocyte-associated transcripts after mTBI.