Blood levels of cytokines highlight the role of inflammation in Alzheimer's disease.

Inflammation and angiogenesis have been defined as potential mechanisms associated with clinical progression from a cognitively normal state to Alzheimer's disease (AD). In this observational case-control study, we aimed to determine plasma levels of cytokines as indicators of inflammation involved in cognitive decline. We measured 30 plasma proteins in 49 controls (CTL), 36 individuals with mild cognitive impairment (MCI) and 52 patients diagnosed with probable AD.

Therapeutic Efficacy of the Inositol D-Pinitol as a Multi-Faceted Disease Modifier in the 5×FAD Humanized Mouse Model of Alzheimer's Amyloidosis.

Background/objectives: Alzheimer's disease (AD), a leading cause of dementia, lacks effective long-term treatments. Current therapies offer temporary relief or fail to halt its progression and are often inaccessible due to cost. AD involves multiple pathological processes, including amyloid beta (Aβ) deposition, insulin resistance, tau protein hyperphosphorylation, and systemic inflammation accelerated by gut microbiota dysbiosis originating from a leaky gut.

The Effect of Fat Intake with Increased Omega-6-to-Omega-3 Polyunsaturated Fatty Acid Ratio in Animal Models of Early and Late Alzheimer's Disease-like Pathogenesis.

This work aims to clarify the effect of dietary polyunsaturated fatty acid (PUFA) intake on the adult brain affected by amyloid pathology. McGill-R-Thy1-APP transgenic (Tg) rat and 5xFAD Tg mouse models that represent earlier or later disease stages were employed. The animals were exposed to a control diet (CD) or an HFD based on corn oil, from young (rats) or adult (mice) ages for 24 or 10 weeks, respectively.

Nicotinamide as potential biomarker for Alzheimer's disease: A translational study based on metabolomics.

The metabolic routes altered in Alzheimer's disease (AD) brain are poorly understood. As the metabolic pathways are evolutionarily conserved, the metabolic profiles carried out in animal models of AD could be directly translated into human studies. We performed untargeted Nuclear Magnetic Resonance metabolomics in hippocampus of McGill-R-Thy1-APP transgenic (Tg) rats, a model of AD-like cerebral amyloidosis and the translational potential of these findings was assessed by targeted Gas Chromatography-Electron Impact-Mass Spectrometry in plasma of participants in the German longitudinal cohort AgeCoDe.

Acute intrahippocampal administration of melanin-concentrating hormone impairs memory consolidation and decreases the expression of MCHR-1 and TrkB receptors.

Interest in the role of melanin-concentrating hormone (MCH) in memory processes has increased in recent years, with some studies reporting memory-enhancing effects, while others report deleterious effects. Due to these discrepancies, this study seeks to provide new evidence about the role of MCH in memory consolidation and its relation with BDNF/TrkB system. To this end, in the first experiment, increased doses of MCH were acutely administered in both hippocampi to groups of male rats (25, 50, 200, and 500 ng).

Nucleoredoxin Plays a Key Role in the Maintenance of Retinal Pigmented Epithelium Differentiation.

Nucleoredoxin (Nrx) belongs to the Thioredoxin protein family and functions in redox-mediated signal transduction. It contains the dithiol active site motif Cys-Pro-Pro-Cys and interacts and regulates different proteins in distinct cellular pathways. Nrx was shown to be catalytically active in the insulin assay and recent findings indicate that Nrx functions, in fact, as oxidase.

Mitochondrial Supercomplexes: Physiological Organization and Dysregulation in Age-Related Neurodegenerative Disorders.

Several studies suggest that the assembly of mitochondrial respiratory complexes into structures known as supercomplexes (SCs) may increase the efficiency of the electron transport chain, reducing the rate of production of reactive oxygen species. Therefore, the study of the (dis)assembly of SCs may be relevant for the understanding of mitochondrial dysfunction reported in brain aging and major neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). Here we briefly reviewed the biogenesis and structural properties of SCs, the impact of mtDNA mutations and mitochondrial dynamics on SCs assembly, the role of lipids on stabilization of SCs and the methodological limitations for the study of SCs.

Thioredoxin 1 Plays a Protective Role in Retinas Exposed to Perinatal Hypoxia-Ischemia.

Thioredoxin family proteins are key modulators of cellular redox regulation and have been linked to several physiological functions, including the cellular response to hypoxia-ischemia. During perinatal hypoxia-ischemia (PHI), the central nervous system is subjected to a fast decrease in O and nutrients with a subsequent reoxygenation that ultimately leads to the production of reactive species impairing physiological redox signaling. Particularly, the retina is one of the most affected tissues, due to its high oxygen consumption and exposure to light.

Environmental enrichment improves cognitive symptoms and pathological features in a focal model of cortical damage of multiple sclerosis.

Multiple Sclerosis (MS) is a neuroinflammatory disease affecting white and grey matter, it is characterized by demyelination, axonal degeneration along with loss of motor, sensitive and cognitive functions. MS is a heterogeneous disease that displays different clinical courses: relapsing/remitting MS (RRMS), and MS progressive forms: primary progressive (PPMS) and secondary progressive (SPMS). Cortical damage in the progressive MS forms has considerable clinical relevance due to its association with cognitive impairment and disability progression in patients.

Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer's disease.

Rare coding variants in TREM2, PLCG2, and ABI3 were recently associated with the susceptibility to Alzheimer's disease (AD) in Caucasians. Frequencies and AD-associated effects of variants differ across ethnicities. To start filling the gap on AD genetics in South America and assess the impact of these variants across ethnicity, we studied these variants in Argentinian population in association with ancestry.

Platelets Bioenergetics Screening Reflects the Impact of Brain Aβ Plaque Accumulation in a Rat Model of Alzheimer.

Alzheimer's disease (AD) is associated to depressed brain energy supply and impaired cortical and hippocampal synaptic function. It was previously reported in McGill-R-Thy1-APP transgenic (Tg(+/+)) rats that Aβ deposition per se is sufficient to cause abnormalities in glucose metabolism and neuronal connectivity. These data support the utility of this animal model as a platform for the search of novel AD biomarkers based on bioenergetic status.

Oleoylethanolamide and Palmitoylethanolamide Protect Cultured Cortical Neurons Against Hypoxia.

Perinatal hypoxic-ischemic (HI) encephalopathy is defined as a neurological syndrome where the newborn suffers from acute ischemia and hypoxia during the perinatal period. New therapies are needed. The acylethanolamides, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), possess neuroprotective properties, and they could be effective against perinatal HI.

Palmitoylethanolamide prevents neuroinflammation, reduces astrogliosis and preserves recognition and spatial memory following induction of neonatal anoxia-ischemia.

Rational: Neonatal anoxia-ischemia (AI) particularly affects the central nervous system. Despite the many treatments that have been tested, none of them has proven to be completely successful. Palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are acylethanolamides that do not bind to CB1 or CB2 receptors and thus they do not present cannabinoid activity.

Chronic Hippocampal Expression of Notch Intracellular Domain Induces Vascular Thickening, Reduces Glucose Availability, and Exacerbates Spatial Memory Deficits in a Rat Model of Early Alzheimer.

The specific roles of Notch in progressive adulthood neurodegenerative disorders have begun to be unraveled in recent years. A number of independent studies have shown significant increases of Notch expression in brains from patients at later stages of sporadic Alzheimer's disease (AD). However, the impact of Notch canonical signaling activation in the pathophysiology of AD is still elusive.

Palmitoylethanolamide attenuates cocaine-induced behavioral sensitization and conditioned place preference in mice.

Cocaine addiction is a chronically relapsing disorder characterized by compulsive drug-seeking and drug-taking behaviors. Previous studies have demonstrated that cocaine, as well as other drugs of abuse, alters the levels of lipid-based signaling molecules, such as N-acylethanolamines (NAEs). Moreover, brain levels of NAEs have shown sensitivity to cocaine self-administration and extinction training in rodents.

Neuronal Damage Induced by Perinatal Asphyxia Is Attenuated by Postinjury Glutaredoxin-2 Administration.

The general disruption of redox signaling following an ischemia-reperfusion episode has been proposed as a crucial component in neuronal death and consequently brain damage. Thioredoxin (Trx) family proteins control redox reactions and ensure protein regulation via specific, oxidative posttranslational modifications as part of cellular signaling processes. Trx proteins function in the manifestation, progression, and recovery following hypoxic/ischemic damage.

Acylethanolamides and endocannabinoid signaling system in dorsal striatum of rats exposed to perinatal asphyxia.

Endocannabinoids (eCBs) and acylethanolamides (AEs) have lately received more attention due to their neuroprotective functions in neurological disorders. Here we analyze the alterations induced by perinatal asphyxia (PA) in the main metabolic enzymes and receptors of the eCBs/AEs in the dorsal striatum of rats. To induce PA, we used a model developed by Bjelke et al.

Worsening of memory deficit induced by energy-dense diet in a rat model of early-Alzheimer's disease is associated to neurotoxic Aβ species and independent of neuroinflammation.

Diet is a modifiable risk factor for Alzheimer's disease (AD), but the mechanisms linking alterations in peripheral metabolism and cognition remain unclear. Since it is especially difficult to study long-term effects of high-energy diet in individuals at risk for AD, we addressed this question by using the McGill-R-Thy1-APP transgenic rat model (Tg(+/-)) that mimics presymptomatic AD. Wild-type and Tg(+/-) rats were exposed during 6months to a standard diet or a Western diet (WD), high in saturated fat and sugar.

Cocaine-induced behavioral sensitization decreases the expression of endocannabinoid signaling-related proteins in the mouse hippocampus.

In the reward mesocorticolimbic circuits, the glutamatergic and endocannabinoid systems are implicated in neurobiological mechanisms underlying cocaine addiction. However, the involvement of both systems in the hippocampus, a critical region to process relational information relevant for encoding drug-associated memories, in cocaine-related behaviors remains unknown. In the present work, we studied whether the hippocampal gene/protein expression of relevant glutamate signaling components, including glutamate-synthesizing enzymes and metabotropic and ionotropic receptors, and the hippocampal gene/protein expression of cannabinoid type 1 (CB1) receptor and endocannabinoid metabolic enzymes were altered following acute and/or repeated cocaine administration resulting in conditioned locomotion and locomotor sensitization.

Synaptosomal bioenergetic defects are associated with cognitive impairment in a transgenic rat model of early Alzheimer's disease.

Synaptic bioenergetic deficiencies may be associated with early Alzheimer's disease (AD). To explore this concept, we assessed pre-synaptic mitochondrial function in hemizygous (+/-)TgMcGill-R-Thy1-APP rats. The low burden of Aβ and the wide array of behavioral and cognitive impairments described in 6-month-old hemizygous TgMcGill-R-Thy1-APP rats (Tg(+/-)) support their use to investigate synaptic bioenergetics deficiencies described in subjects with early Alzheimer's disease (AD).

Perinatal asphyxia results in altered expression of the hippocampal acylethanolamide/endocannabinoid signaling system associated to memory impairments in postweaned rats.

Perinatal asphyxia (PA) is an obstetric complication that strongly affects the CNS. The endocannabinoid system (ECS) is a lipid transmitter system involved in several physiological processes including synaptic plasticity, neurogenesis, memory, and mood. Endocannabinoids, and other acylethanolamides (AEs) without endocannabinoid activity, have recently received growing attention due to their potential neuroprotective functions in neurological disorders, including cerebral ischemia.

Life-long environmental enrichment counteracts spatial learning, reference and working memory deficits in middle-aged rats subjected to perinatal asphyxia.

Continuous environmental stimulation induced by exposure to enriched environment (EE) has yielded cognitive benefits in different models of brain injury. Perinatal asphyxia results from a lack of oxygen supply to the fetus and is associated with long-lasting neurological deficits. However, the effects of EE in middle-aged rats suffering perinatal asphyxia are unknown.

Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer's disease.

Intraneuronal accumulation of amyloid β (iAβ) has been linked to mild cognitive impairment that may precede Alzheimer's disease (AD) onset. This neuropathological trait was recently mimicked in a novel animal model of AD, the hemizygous transgenic McGill-R-Thy1-APP (Tg(+/-)) rat. The characterization of the behavioral phenotypes in this animal model could provide a baseline of efficacy for earlier therapeutic interventions.