Endolysosomal dysfunction in radial glia progenitor cells leads to defective cerebral angiogenesis and compromised blood-brain barrier integrity.

The neurovascular unit (NVU) is a complex multicellular structure that helps maintain cerebral homeostasis and blood-brain barrier (BBB) integrity. While extensive evidence links NVU alterations to cerebrovascular diseases and neurodegeneration, the underlying molecular mechanisms remain unclear. Here, we use zebrafish embryos carrying a mutation in Scavenger Receptor B2, a highly conserved endolysosomal protein expressed predominantly in Radial Glia Cells (RGCs), to investigate the interplay among different NVU components.

Biflavonoid Methylchamaejasmin and Khaya grandifoliola Extract Inhibit NLRP3 Inflammasome in THP-1 Cell Model of Neuroinflammation.

Neuroinflammation is a common hallmark of Alzheimer's disease (AD), with NLRP3 inflammasome proven to be activated in microglia of AD patients' brains. In this study, a newly isolated biflavonoid (7,7'-di-O-methylchamaejasmin/M8) and a crude extract of the plant Khaya grandifoliola (KG) were investigated for their inhibitory effect on inflammasome activation. In preliminary experiments, M8 and KG showed no cytotoxicity on human macrophage-like differentiated THP-1 cells and exhibited anti-inflammatory inhibition of nitric oxide produced following lipopolysaccharide stimulation.

Different inflammatory signatures based on CSF biomarkers relate to preserved or diminished brain structure and cognition.

Neuroinflammation is a hallmark of Alzheimer's disease (AD) and both positive and negative associations of individual inflammation-related markers with brain structure and cognitive function have been described. We aimed to identify inflammatory signatures of CSF immune-related markers that relate to changes of brain structure and cognition across the clinical spectrum ranging from normal aging to AD. A panel of 16 inflammatory markers, Aβ42/40 and p-tau181 were measured in CSF at baseline in the DZNE DELCODE cohort (n = 295); a longitudinal observational study focusing on at-risk stages of AD.

Inflammasomes in neurological disorders - mechanisms and therapeutic potential.

Inflammasomes are molecular scaffolds that are activated by damage-associated and pathogen-associated molecular patterns and form a key element of innate immune responses. Consequently, the involvement of inflammasomes in several diseases that are characterized by inflammatory processes, such as multiple sclerosis, is widely appreciated. However, many other neurological conditions, including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, stroke, epilepsy, traumatic brain injury, sepsis-associated encephalopathy and neurological sequelae of COVID-19, all involve persistent inflammation in the brain, and increasing evidence suggests that inflammasome activation contributes to disease progression in these conditions.

NLRP3-directed antisense oligonucleotides reduce microglial immunoactivities in vitro.

Alzheimer's disease (AD) is associated with the cerebral deposition of Amyloid-β (Aβ) peptide, which leads to NLRP3 inflammasome activation and subsequent release of interleukin-1β (IL-1β) and interleukin-18 (IL-18). NLRP3 reduction has been found to increase microglial clearance, protect from synapse loss, and suppress both the changes to synaptic plasticity and spatial memory dysfunction observed in murine AD models. Here, we test whether NLRP3-directed antisense oligonucleotides (ASOs) can be harnessed as immune modulators in primary murine microglia and human THP-1 cells.

Chronic low-dose Δ-tetrahydrocannabinol (THC) treatment stabilizes dendritic spines in 18-month-old mice.

Cognitive functions decline during aging. This decline could be caused by changes in dendritic spine stability and altered spine dynamics. Previously, we have shown that a low dose chronic THC treatment improves learning abilities in old whereas impairs learning abilities in young mice.

Serum IL-6, sAXL, and YKL-40 as systemic correlates of reduced brain structure and function in Alzheimer's disease: results from the DELCODE study.

Background: Neuroinflammation constitutes a pathological hallmark of Alzheimer's disease (AD). Still, it remains unresolved if peripheral inflammatory markers can be utilized for research purposes similar to blood-based beta-amyloid and neurodegeneration measures. We investigated experimental inflammation markers in serum and analyzed interrelations towards AD pathology features in a cohort with a focus on at-risk stages of AD.

Soluble TAM receptors sAXL and sTyro3 predict structural and functional protection in Alzheimer's disease.

There is an urgent need to improve the understanding of neuroinflammation in Alzheimer's disease (AD). We analyzed cerebrospinal fluid inflammatory biomarker correlations to brain structural volume and longitudinal cognitive outcomes in the DELCODE study and in a validation cohort of the F.ACE Alzheimer Center Barcelona.

Inflammasome activation in neurodegenerative diseases.

Approximately ten million people are diagnosed with dementia annually since they experience difficulties with memory and thinking skills. Since neurodegenerative diseases are diagnosed late, most of them are difficult to treat. This is due to the increased severity of the disease during the progression when neuroinflammation plays a critical role.

Cannabinoid receptor 2 is necessary to induce toll-like receptor-mediated microglial activation.

The tight regulation of microglia activity is key for precise responses to potential threats, while uncontrolled and exacerbated microglial activity is neurotoxic. Microglial toll-like receptors (TLRs) are indispensable for sensing different types of assaults and triggering an innate immune response. Cannabinoid receptor 2 (CB2) signaling is a key pathway to control microglial homeostasis and activation, and its activation is connected to changes in microglial activity.

Cannabinoid receptor 2 deletion influences social memory and synaptic architecture in the hippocampus.

Although the cannabinoid receptor 2 (CBR) is often thought to play a role mainly outside the brain several publications unequivocally showed the presence of CBR on hippocampal principal neurons. Activation of CBR produced a long-lasting membrane potential hyperpolarization, altered the input/output function of CA2/3 principal neurons and produced alterations in gamma oscillations. However, other cellular, molecular and behavioral consequences of hippocampal CBR signaling have not been studied in detail.

Virgin coconut oil supplementation in diet modulates immunity mediated through survival signaling pathways in rats.

Background Virgin coconut oil (VCO), a cold processed form of coconut oil, is traditionally consumed in Asian countries owing to its nutritional and medicinal properties. The aim of this study was to investigate whether the health benefits of VCO involve alterations in immune responses that are regulated by intracellular signaling molecules in the spleens of rats. Methods Young male Wistar rats were fed with three doses of VCO in diet for 30 days.