The Impact of High-Dose Fish Oil Supplementation on Mfsd2a, Aqp4, and Amyloid-β Expression in Retinal Blood Vessels of 5xFAD Alzheimer's Mouse Model.

In patients with Alzheimer's disease (AD) and in animal models, the increased accumulation of amyloid β (Aβ) in retinal blood vessels strongly correlates with brain amyloid deposits and cognitive decline. The accumulation of Aβ in blood vessels may result from impaired transcytosis and a dysfunctional ocular glymphatic system in AD. High-dose fish oil (FO) supplementation has been shown to significantly change the expression of major facilitator superfamily domain-containing protein 2a (Mfsd2a), a key regulator of transcytosis, and Aquaporin 4 (Aqp4), an essential component of the glymphatic system in the retinas of WT mice.

Ketamine's Amelioration of Fear Extinction in Adolescent Male Mice Is Associated with the Activation of the Hippocampal Akt-mTOR-GluA1 Pathway.

Fear-related disorders, including post-traumatic stress disorder (PTSD), and anxiety disorders are pervasive psychiatric conditions marked by persistent fear, stemming from its dysregulated acquisition and extinction. The primary treatment for these disorders, exposure therapy (ET), relies heavily on fear extinction (FE) principles. Adolescence, a vulnerable period for developing psychiatric disorders, is characterized by neurobiological changes in the fear circuitry, leading to impaired FE and increased susceptibility to relapse following ET.

Reduced light exposure mitigates streptozotocin-induced vascular changes and gliosis in diabetic retina by an anti-inflammatory effect and increased retinal cholesterol turnover.

Diabetic retinopathy is not cured efficiently and changes of lifestyle measures may delay early retinal injury in diabetes. The aim of our study was to investigate the effects of reduced daily light exposure on retinal vascular changes in streptozotocin (STZ)-induced model of DM with emphasis on inflammation, Aqp4 expression, visual cycle and cholesterol metabolism-related gene expression in rat retina and RPE. Male Wistar rats were divided into the following groups: 1.

Nanocarriers in topical photodynamic therapy.

Introduction: Photodynamic therapy (PDT) has gained significant attention due to its superiority over conventional treatments. In the context of skin cancers and nonmalignant skin diseases, topical application of photosensitizer formulations onto affected skin, followed by illumination, offers distinct advantages. Topical PDT simplifies therapy by providing easy access to the skin, increasing drug concentration within the target area, and confining residual photosensitivity to the treated skin.

The supplementation of a high dose of fish oil during pregnancy and lactation led to an elevation in Mfsd2a expression without any changes in docosahexaenoic acid levels in the retina of healthy 2-month-old mouse offspring.

Introduction: During fetal development, the proper development of neural and visual systems relies on the maternal supplementation of omega-3 fatty acids through placental transfer. Pregnant women are strongly advised to augment their diet with additional sources of omega-3, such as fish oil (FO). This supplementation has been linked to a reduced risk of preterm birth, pre-eclampsia, and perinatal depression.

Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus.

Zaleplon is a positive allosteric modulator of the γ-aminobutyric acid (GABA) receptor approved for the short-term treatment of insomnia. Previous publications on zaleplon have not addressed the proteins involved in its mechanism of action but have mostly referred to behavioral or pharmacological studies. Since both GABAergic and glutamatergic signaling have been shown to regulate wakefulness and sleep, we examined the effects of prolonged zaleplon treatment (0.

The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer's Disease.

Cerebral amyloid angiopathy (CAA) is characterized by amyloid β (Aβ) accumulation in the blood vessels and is associated with cognitive impairment in Alzheimer's disease (AD). The increased accumulation of Aβ is also present in the retinal blood vessels and a significant correlation between retinal and brain amyloid deposition was demonstrated in living patients and animal AD models. The Aβ accumulation in the retinal blood vessels can be the result of impaired transcytosis and/or the dysfunctional ocular glymphatic system in AD and during aging.

Shortened Daily Photoperiod Alleviates Anxiety-like Behaviour by Antioxidant Effect and Changes Serum Fatty Acid Profile in Diabetic Rats.

The aim of our study was to investigate the effects of a shortened daily photoperiod on anxiety-like behaviour, brain oxidative stress, lipid status and fatty acid composition of serum lipids in a streptozotocin (STZ)-induced model of diabetes mellitus in rats. Male Wistar rats were divided into the following groups: first group-control group (C); second group-diabetic group (DM; 100 mg/kg STZ); third group-control group exposed to a light/dark cycle 6/18 h (C); fourth group-diabetic group exposed to a light/dark cycle 6/18 h (DM). Anxiety-like behaviour was tested three weeks following STZ injection by elevated plus maze (EPM) and open-field test (OFT).

The presymptomatic treatment with 3HFWC nanosubstance decreased plaque load in 5XFAD mouse model of Alzheimer's disease.

Introduction: In the present study, we assessed the effects of the hyper-harmonized-hydroxylated fullerene-water complex (3HFWC) on Alzheimer's disease (AD) neuropathological hallmarks in 5XFAD mice, an AD animal model.

Methods: The 3-week-old 5XFAD mice were exposed to 3HFWC water solution ad libitum for 3 months in the presymptomatic phase of pathology. The functional effects of the treatment were confirmed through near-infrared spectroscopy (NIRS) analysis through machine learning (ML) using artificial neural networks (ANNs) to classify the control and 3HFWC-treated brain tissue samples.

Food Restriction Counteracts Dexamethasone-Induced Downregulation of Genes Involved in Cholesterol Homeostasis in Rat Brain during Aging.

Glucocorticoids are the most potent anti-inflammatory agents known. Limited in vivo data are available to characterize the mechanism underlying their cognitive side effects and transient occurrence of steroid psychosis. Cholesterol is important for proper neurotransmission and brain plasticity, and disruption of its homeostasis in the brain has been closely associated with memory decline during aging and in age-related neurodegenerative disorders.

Tryptophan metabolites in depression: Modulation by gut microbiota.

Clinical depression is a multifactorial disorder and one of the leading causes of disability worldwide. The alterations in tryptophan metabolism such as changes in the levels of serotonin, kynurenine, and kynurenine acid have been implicated in the etiology of depression for more than 50 years. In recent years, accumulated evidence has revealed that gut microbial communities, besides being essential players in various aspects of host physiology and brain functioning are also implicated in the etiology of depression, particularly through modulation of tryptophan metabolism.

Fatty acids as biomodulators of Piezo1 mediated glial mechanosensitivity in Alzheimer's disease.

The brain is the softest organ in the body, and any change in the mechanical properties of the tissue induces the activation of glial cells, astrocytes and microglia. Amyloid plaques, one of the main pathological features of Alzheimer's disease (AD), are substantially harder than the surrounding brain tissue and can activate astrocytes and microglia resulting in the glial engulfment of plaques. Durotaxis, a migratory preference towards stiffer tissue, is prompting microglia to form a mechanical barrier around plaques reducing amyloid β (Aβ) induced neurotoxicity.

From chronic stress and anxiety to neurodegeneration: Focus on neuromodulation of the axon initial segment.

To adapt to the sustained demands of chronic stress, discrete brain circuits undergo structural and functional changes often resulting in anxiety disorders. In some individuals, anxiety disorders precede the development of motor symptoms of Parkinson's disease (PD) caused by degeneration of neurons in the substantia nigra (SN). Here, we present a circuit framework for probing a causal link between chronic stress, anxiety, and PD, which postulates a central role of abnormal neuromodulation of the SN's axon initial segment by brainstem inputs.

Short-term fish oil supplementation applied in presymptomatic stage of Alzheimer's disease enhances microglial/macrophage barrier and prevents neuritic dystrophy in parietal cortex of 5xFAD mouse model.

Dystrophic neurites and activated microglia are one of the main neuropathological characteristics of Alzheimer's disease (AD). Although the use of supplements with omega-3 fatty acids has been associated with reduced risk and lessened AD pathology, it still remains elusive whether such a treatment could affect dystrophic neurites (DNs) formation and microglia/macrophage behavior in the early phase of disease. We analyzed the effects of short-term (3 weeks) fish oil supplementation on DNs formation, tau hyperphosphorylation, Amyloid-beta peptide 1-42 (Aβ42) levels and microglial/macrophage response to AD pathology in the parietal cortex of 4-month-old 5xFAD mice, a mouse model of AD.

Short-Term Fish Oil Treatment Changes the Composition of Phospholipids While Not Affecting the Expression of Mfsd2a Omega-3 Transporter in the Brain and Liver of the 5xFAD Mouse Model of Alzheimer's Disease.

Long-term fish oil (FO) supplementation is able to improve Alzheimer's disease (AD) pathology. We aimed to determine the impact of short-term fish oil (FO) intake on phospholipids composition and plaque pathology in 5xFAD mice, a widely used animal model of AD. A 3-week-long FO supplementation administered at 3 months of age decreased the number of dense core plaques in the 5xFAD cortex and changed phospholipids in the livers and brains of wild-type (Wt) and 5xFAD mice.

Limited daily feeding and intermittent feeding have different effects on regional brain energy homeostasis during aging.

Albeit aging is an inevitable process, the rate of aging is susceptible to modifications. Dietary restriction (DR) is a vigorous nongenetic and nonpharmacological intervention that is known to delay aging and increase healthspan in diverse species. This study aimed to compare the impact of different restricting feeding regimes such as limited daily feeding (LDF, 60% AL) and intermittent feeding (IF) on brain energy homeostasis during aging.

Cholesterol metabolism changes under long-term dietary restrictions while the cholesterol homeostasis remains unaffected in the cortex and hippocampus of aging rats.

Maintaining cholesterol homeostasis in the brain is vital for its proper functioning. While it is well documented that dietary restriction modulates the metabolism of cholesterol peripherally, little is known as to how it can affect cholesterol metabolism in the brain. The present study was designed to elucidate the impact of long-term dietary restriction on brain cholesterol metabolism.

Direct inhibition of myosin II effectively blocks glioma invasion in the presence of multiple motogens.

Anaplastic gliomas, the most common and malignant of primary brain tumors, frequently contain activating mutations and amplifications in promigratory signal transduction pathways. However, targeting these pathways with individual signal transduction inhibitors does not appreciably reduce tumor invasion, because these pathways are redundant; blockade of any one pathway can be overcome by stimulation of another. This implies that a more effective approach would be to target a component at which these pathways converge.

Constitutive EGFR signaling in oligodendrocyte progenitors leads to diffuse hyperplasia in postnatal white matter.

Gliogenesis requires the careful orchestration of migration, differentiation, and proliferation of progenitors. Signaling through the epidermal growth factor receptor (EGFR) has been implicated in regulating these processes in a variety of cell types, including neural progenitors. By retroviral infection, we constitutively expressed an EGFR-GFP fusion protein in white matter glial progenitors at postnatal day 3 of the rat forebrain in vivo and analyzed the development of these cells over the subsequent 15 weeks.

DARPP-32 genomic fragments drive Cre expression in postnatal striatum.

To direct Cre-mediated recombination to differentiated medium-size spiny neurons (MSNs) of the striatum, we generated transgenic mice that express Cre recombinase under the regulation of DARPP-32 genomic fragments. In this reported line, recombination of an R26R reporter allele occurred postnatally in the majority of medium-size spiny neurons of the dorsal and ventral striatum (caudate nucleus and nucleus accumbens/olfactory tubercle), as well as in the piriform cortex and choroid plexus. Although regulatory fragments were selected to target MSNs, low levels of Cre-recombinase expression, as detected by beta-galactosidase activity from the R26R reporter gene, were also apparent in widely dispersed areas or cells of the forebrain and hindbrain.

Prenatal exposure to cocaine decreases adenylyl cyclase activity in embryonic mouse striatum.

Adenylyl cyclase activity was measured in the striatum of naive mice as a function of age and in mice exposed in utero to cocaine. In naive Swiss-Webster mice, basal and forskolin-stimulated adenylyl cyclase activity increased gradually from embryonic day 13 (E13) until 2-3 weeks of age when activity peaked before decreasing slightly to adult levels. The ability of the dopamine D1 receptor agonist, SKF 82958, to stimulate adenylyl cyclase activity also increased in magnitude until P15.

Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development.

Coordinated production and remodeling of the extracellular matrix is essential during development. It is of particular importance for skeletogenesis, as the ability of cartilage and bone to provide structural support is determined by the composition and organization of the extracellular matrix. Connective tissue growth factor (CTGF, CCN2) is a secreted protein containing several domains that mediate interactions with growth factors, integrins and extracellular matrix components.

Autoregulation of neurogenesis by GDF11.

In the olfactory epithelium (OE), generation of new neurons by neuronal progenitors is inhibited by a signal from neurons themselves. Here we provide evidence that this feedback inhibitory signal is growth and differentiation factor 11 (GDF11). Both GDF11 and its receptors are expressed by OE neurons and progenitors, and GDF11 inhibits OE neurogenesis in vitro by inducing p27(Kip1) and reversible cell cycle arrest in progenitors.