Heterogeneity in Slow Synaptic Transmission Diversifies Purkinje Cell Timing.

The cerebellum plays an important role in diverse brain functions, ranging from motor learning to cognition. Recent studies have suggested that molecular and cellular heterogeneity within cerebellar lobules contributes to functional differences across the cerebellum. However, the specific relationship between molecular and cellular heterogeneity and diverse functional outputs of different regions of the cerebellum remains unclear.

Combination Treatment With Varenicline and Nicotine Patch on Smoking Cessation Outcomes in Heavy Drinkers at 26-Week Follow-up.

Purpose/background: People who smoke cigarettes and drink alcohol heavily are less likely to quit smoking compared with those who do not drink heavily. The current study examined the effects of a 12-week treatment phase of combination varenicline and nicotine patch compared with placebo and nicotine patch on smoking cessation (primary outcome) and alcohol consumption (secondary outcome) in heavy drinking smokers at 26-week follow-up.

Methods/procedures: Participants were daily smokers who met heavy drinking criteria.

Subcellular functions of tau mediates repair response and synaptic homeostasis in injury.

Injury responses in terminally differentiated cells such as neurons is tightly regulated by pathways aiding homeostatic maintenance. Cancer patients subjected to neuronal injury in brain radiation experience cognitive declines similar to those seen in primary neurodegenerative diseases. Numerous studies have investigated the effect of radiation in proliferating cells of the brain, yet the impact in differentiated, post-mitotic neurons, especially the structural and functional alterations remain largely elusive.

MGMT function determines the differential response of ATR inhibitors with DNA-damaging agents in glioma stem cells for GBM therapy.

Background: The most prevalent cancer treatments cause cell death through DNA damage. However, DNA damage response (DDR) repair pathways, initiated by tumor cells, can withstand the effects of anticancer drugs, providing justification for combining DDR inhibitors with DNA-damaging anticancer treatments.

Methods: Cell viability assays were performed with CellTiter-Glo assay.

Catecholamine Vasopressor Exposure Is Associated With Early Poor Allograft Function and Adverse Events in Living Donor Kidney Transplant Recipients.

Background: Hypoperfusion leads to allograft injury during kidney transplantation. Catecholamine vasopressors are used to maintain blood pressure in the perioperative period but have demonstrated negative outcomes in the deceased-donor kidney transplant population. Little is known regarding living donor kidney transplants (LDKTs) and vasopressor use.

User experiences of an American-adapted moderated online social media platform for first-episode psychosis: Qualitative analysis.

Objectives: The current study sought to qualitatively characterize the experiences of American users in a recent open trial of the Horyzons digital platform.

Methods: In total, 20 users on Horyzons USA completed semistructured interviews 12 weeks after their orientation to the platform and addressed questions related to (1) the platform, (2) their online therapist, and (3) the peer workers and community space. A hybrid inductive-deductive coding strategy was used to conduct a thematic analysis of the data (NCT04673851).

Heteroatom engineered graphene-based electrochemical assay for the quantification of high-risk abused drug oxytocin in edibles and biological samples.

The naive detection of scheduled H drug oxytocin is a vital requisite, owing to its deleterious impact on societal affluence prompted by unconstrained usage. Therefore, a reliable, cost-effective, and quick-to-respond analytic technique for this drug is in ample demand. In this work, we report electrochemical detection of oxytocin employing novel nitrogen, phosphorus co-doped coke-derived graphene (NPG) modified electrode.

Mesoporous onion-like carbon nanostructures from natural oil for high-performance supercapacitor and electrochemical sensing applications: Insights into the post-synthesis sonochemical treatment on the electrochemical performance.

Although onion-like carbon nanostructures (OLCs) are attractive materials for energy storage, their commercialization is hampered by the absence of a simple, cost-effective, large-scale synthesis route and binder-free electrode processing. The present study employs a scalable and straightforward technique to fabricate sonochemically tailored OLCs-based high-performance supercapacitor electrode material. An enhanced supercapacitive performance was demonstrated by the OLCs when sonicated in DMF at 60 °C for 15 min, with a specific capacitance of 647 F/g, capacitance retention of 97% for 5000 cycles, and a charge transfer resistance of 3 Ω.

Ensconsin-dependent changes in microtubule organization and LINC complex-dependent changes in nucleus-nucleus interactions result in quantitatively distinct myonuclear positioning defects.

Nuclear movement is a fundamental process of eukaryotic cell biology. Skeletal muscle presents an intriguing model to study nuclear movement because its development requires the precise positioning of multiple nuclei within a single cytoplasm. Furthermore, there is a high correlation between aberrant nuclear positioning and poor muscle function.

4E-BP2-dependent translation in cerebellar Purkinje cells controls spatial memory but not autism-like behaviors.

Recent studies have demonstrated that selective activation of mammalian target of rapamycin complex 1 (mTORC1) in the cerebellum by deletion of the mTORC1 upstream repressors TSC1 or phosphatase and tensin homolog (PTEN) in Purkinje cells (PCs) causes autism-like features and cognitive deficits. However, the molecular mechanisms by which overactivated mTORC1 in the cerebellum engenders these behaviors remain unknown. The eukaryotic translation initiation factor 4E-binding protein 2 (4E-BP2) is a central translational repressor downstream of mTORC1.

Epidermal growth factor treatment of female mice that express at an age of advanced pathology mitigates behavioral and cerebrovascular dysfunction.

is a major genetic risk factor for Alzheimer's disease and high amyloid-β (Aβ) levels in the brain are a pathological hallmark of the disease. However, the contribution of specific -modulated Aβ-dependent and Aβ-independent functions to cognitive decline remain unclear. Increasing evidence supports a role of in modulating cerebrovascular function, however whether ameliorating this dysfunction can improve behavioral function is still under debate.

Exercise Training Results in Lower Amyloid Plaque Load and Greater Cognitive Function in an Intensity Dependent Manner in the Tg2576 Mouse Model of Alzheimer's Disease.

Three months of exercise training (ET) decreases soluble Aβ and Aβ levels in an intensity dependent manner early in life in Tg2576 mice (Moore et al., 2016). Here, we examined the effects of 12 months of low- and high- intensity exercise training on cognitive function and amyloid plaque load in the cortex and hippocampus of 15-month-old Tg2576 mice.

Evaluation of B-correction of relative CBF maps using tagging distance dependent Z-spectrum (TADDZ).

Arterial spin labeling (ASL) MRI, based on endogenous contrast from blood water, is used in research and diagnosis of cerebral vascular conditions. However, artifacts due to imperfect imaging conditions such as B-inhomogeneity (ΔB) could lead to variations in the quantification of relative cerebral blood flow (CBF). In this study, we evaluate a new approach using tagging distance dependent Z-spectrum (TADDZ) data, similar to the ΔB corrections in the chemical exchange saturation transfer (CEST) experiments, to remove the imaging plane B inhomogeneity induced CBF artifacts in ASL MRI.

Dietary docosahexaenoic acid (DHA) as lysophosphatidylcholine, but not as free acid, enriches brain DHA and improves memory in adult mice.

Docosahexaenoic acid (DHA) is uniquely concentrated in the brain, and is essential for its function, but must be mostly acquired from diet. Most of the current supplements of DHA, including fish oil and krill oil, do not significantly increase brain DHA, because they are hydrolyzed to free DHA and are absorbed as triacylglycerol, whereas the transporter at blood brain barrier is specific for phospholipid form of DHA. Here we show that oral administration of DHA to normal adult mice as lysophosphatidylcholine (LPC) (40 mg DHA/kg) for 30 days increased DHA content of the brain by >2-fold.

Peripheral Inflammation, Apolipoprotein E4, and Amyloid-β Interact to Induce Cognitive and Cerebrovascular Dysfunction.

Cerebrovascular dysfunction is rapidly reemerging as a major process of Alzheimer's disease (AD). It is, therefore, crucial to delineate the roles of AD risk factors in cerebrovascular dysfunction. While apolipoprotein E4 ( APOE4), Amyloid-β (Aβ), and peripheral inflammation independently induce cerebrovascular damage, their collective effects remain to be elucidated.

In Vitro Assays to Assess Blood-brain Barrier Mesh-like Vessel Formation and Disruption.

Blood-brain barrier (BBB) coverage plays a central role in the homeostasis of the central nervous system (CNS). The BBB is dynamically maintained by astrocytes, pericytes and brain endothelial cells (BECs). Here, we detail methods to assess BBB coverage using single cultures of immortalized human BECs, single cultures of primary mouse BECs, and a humanized triple culture model (BECs, astrocytes and pericytes) of the BBB.

Epidermal growth factor prevents -induced cognitive and cerebrovascular deficits in female mice.

Cerebrovascular dysfunction is re-emerging as a major component of aging, and may contribute to the risk of developing Alzheimer's disease (AD). Two important risk factors for cerebrovascular dysfunction are and female sex, which are primarily researched in the context of high amyloid-β (Aβ) levels as found in AD. However, and sex modulate Aβ-independent pathways that may induce cerebrovascular dysfunction as a downstream consequence.

EFAD transgenic mice as a human relevant preclinical model of Alzheimer's disease.

Identified in 1993, is the greatest genetic risk factor for sporadic Alzheimer's disease (AD), increasing risk up to 15-fold compared with , with decreasing AD risk. However, the functional effects of on AD pathology remain unclear and, in some cases, controversial. In vivo progress to understand how the human (h)- genotypes affect AD pathology has been limited by the lack of a tractable familial AD-transgenic (FAD-Tg) mouse model expressing h- rather than mouse (m)- The disparity between m- and h-apoE is relevant for virtually every AD-relevant pathway, including amyloid-β (Aβ) deposition and clearance, neuroinflammation, tau pathology, neural plasticity and cerebrovascular deficits.

Epidermal growth factor prevents oligomeric amyloid-β induced angiogenesis deficits in vitro.

Cerebrovascular dysfunction is a critical component of Alzheimer's disease (AD) pathogenesis. Oligomeric amyloid-β42 (oAβ42) is considered a major contributor to AD progression. However, data are limited on the role of oAβ42 in brain endothelial cell vessel degeneration/angiogenesis, including the interaction with angiogenic mediators.

Epidermal growth factor prevents APOE4 and amyloid-beta-induced cognitive and cerebrovascular deficits in female mice.

Cerebrovascular (CV) dysfunction is emerging as a critical component of Alzheimer's disease (AD), including altered CV coverage. Angiogenic growth factors (AGFs) are key for controlling CV coverage, especially during disease pathology. Therefore, evaluating the effects of AGFs in vivo can provide important information on the role of CV coverage in AD.

The role of APOE in cerebrovascular dysfunction.

The ε4 allele of the apolipoprotein E gene (APOE4) is associated with cognitive decline during aging, is the greatest genetic risk factor for Alzheimer's disease and has links to other neurodegenerative conditions that affect cognition. Increasing evidence indicates that APOE genotypes differentially modulate the function of the cerebrovasculature (CV), with apoE and its receptors expressed by different cell types at the CV interface (astrocytes, pericytes, smooth muscle cells, brain endothelial cells). However, research on the role of apoE in CV dysfunction has not advanced as quickly as other apoE-modulated pathways.