Nose to brain strategy coupled to nano vesicular system for natural products delivery: Focus on synaptic plasticity in Alzheimer's disease.

A wide number of natural molecules demonstrated neuroprotective effects on synaptic plasticity defects induced by amyloid-β (Aβ) in and Alzheimer's disease (AD) models, suggesting a possible use in the treatment of this neurodegenerative disorder. However, several compounds, administered parenterally and orally, are unable to reach the brain due to the presence of the blood-brain barrier (BBB) which prevents the passage of external substances, such as proteins, peptides, or phytocompounds, representing a limit to the development of treatment for neurodegenerative diseases, such as AD. The combination of nano vesicular systems, as colloidal systems, and nose to brain (NtB) delivery depicts a new nanotechnological strategy to overtake this limit and to develop new treatment approaches for brain diseases, including the use of natural molecules in combination therapy for AD.

Landmark Positioning on a Map: An Alternative Measure of Spatial Ability for Identifying Students Who May Benefit From Learning Gross Anatomy with Virtual Reality.

Research has shown an inconsistent relationship between spatial abilities and learning outcomes from virtual anatomical tools. Instructors must understand this relationship to select appropriate resources for diverse learners. To identify appropriate tests for measuring spatial ability and evaluate the effectiveness of virtual anatomical resources, this study compared 96 students' visuospatial ability (measured using the Mental Rotation Task [MRT] and Landmark Position on a Map [LPM] tests) with learning outcomes from experimental anatomy sessions and undergraduate anatomical course examinations.

Switch to phagocytic microglia by CSFR1 inhibition drives amyloid-beta clearance from glutamatergic terminals rescuing LTP in acute hippocampal slices.

Microglia, traditionally regarded as innate immune cells in the brain, drive neuroinflammation and synaptic dysfunctions in the early phases of Alzheimer disease (AD), acting upstream to Aβ accumulation. Colony stimulating factor 1-receptor (CSF-1R) is predominantly expressed on microglia and its levels are significantly increased in neurodegenerative diseases, possibly contributing to the chronic inflammatory microglial response. On the other hand, CSF-1R inhibitors confer neuroprotection in preclinical models of neurodegenerative diseases.

Relationship between the relative timing of prosection and dissection experiences and laboratory examination performance in a gross anatomy course.

Reduced hours of instruction are reported within the gross anatomy education literature. Anatomy instruction continues to be challenged with motivating and inspiring learners to value the contribution of gross anatomy knowledge to their career development alongside increased organizational demands for efficiency and effectiveness. To address these demands, this retrospective study sought to understand how the relative timing and amount of gross anatomy instruction were related to examination performance.

Updates on the Physiopathology of Group I Metabotropic Glutamate Receptors (mGluRI)-Dependent Long-Term Depression.

Group I metabotropic glutamate receptors (mGluRI), including mGluR1 and mGluR5 subtypes, modulate essential brain functions by affecting neuronal excitability, intracellular calcium dynamics, protein synthesis, dendritic spine formation, and synaptic transmission and plasticity. Nowadays, it is well appreciated that the mGluRI-dependent long-term depression (LTD) of glutamatergic synaptic transmission (mGluRI-LTD) is a key mechanism by which mGluRI shapes connectivity in various cerebral circuitries, directing complex brain functions and behaviors, and that it is deranged in several neurological and psychiatric illnesses, including neurodevelopmental disorders, neurodegenerative diseases, and psychopathologies. Here, we will provide an updated overview of the physiopathology of mGluRI-LTD, by describing mechanisms of induction and regulation by endogenous mGluRI interactors, as well as functional physiological implications and pathological deviations.

Influence of Cortisol on the Fibril Formation Kinetics of Aβ42 Peptide: A Multi-Technical Approach.

Amyloid-β peptide (Aβ) aggregates are known to be correlated with pathological neurodegenerative diseases. The fibril formation process of such peptides in solution is influenced by several factors, such as the ionic strength of the buffer, concentration, pH, and presence of other molecules, just to mention a few. In this paper, we report a detailed analysis of in vitro Aβ42 fibril formation in the presence of cortisol at different relative concentrations.

How Virtual Animal Anatomy facilitated a successful transition to online instruction and supported student learning during the coronavirus pandemic.

Anatomy faculty with cadaver-based laboratory courses were presented with a significant challenge in March 2020 to create equivalent learning experiences without cadaveric access. The undergraduate domestic animal anatomy course at the Colorado State University was halfway into a 16-week semester when COVID-19 lockdown orders and the transition to remote instruction began. The new course curriculum was critically evaluated using student surveys and course outcome data.

Learning Monologues at Bedtime Improves Sleep Quality in Actors and Non-Actors.

Several studies show that pre-sleep learning determines changes in subsequent sleep, including improvements of sleep quality. Our aims were to confirm this finding using a more ecological task (learning a theatrical monologue) and to investigate whether the effect is modulated by expertise. Using a mixed design, we compared polysomnographic recordings of baseline sleep (BL, 9-h TIB) to those of post-training sleep (TR, with the same TIB but preceded by the training session), in one group of actors ( = 11) and one of non-actors ( = 11).

Neurodegenerative Disease: What Potential Therapeutic Role of Acid-Sensing Ion Channels?

Acidic pH shift occurs in many physiological neuronal activities such as synaptic transmission and synaptic plasticity but also represents a characteristic feature of many pathological conditions including inflammation and ischemia. Neuroinflammation is a complex process that occurs in various neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and Huntington's disease. Acid-sensing ion channels (ASICs) represent a widely expressed pH sensor in the brain that play a key role in neuroinflammation.

Targeting Microglia-Synapse Interactions in Alzheimer's Disease.

In this review, we focus on the emerging roles of microglia in the brain, with particular attention to synaptic plasticity in health and disease. We present evidence that ramified microglia, classically believed to be "resting" (i.e.

Ceftriaxone- and ceftazidime-resistant species, , and methicillin-resistant dominate caesarean surgical site infections at Mulago Hospital, Kampala, Uganda.

Objectives: The aim of this study was to determine the proportion and mechanism of resistance to ceftriaxone and ceftazidime among species and and examine the burden of methicillin-resistant from caesarean section surgical site infections in Uganda.

Methods: Wound swabs from 109 caesarean section surgical site infections were cultured for pathogenic bacteria following standard microbiological procedures. The Kirby-Bauer disc diffusion technique was used for antimicrobial susceptibility testing.

Role of ASIC1a in Normal and Pathological Synaptic Plasticity.

Acid-sensing ion channels (ASICs), members of the degenerin/epithelial Na+ channel superfamily, are broadly distributed in the mammalian nervous system where they play important roles in a variety of physiological processes, including neurotransmission and memory-related behaviors. In the last few years, we and others have investigated the role of ASIC1a in different forms of synaptic plasticity especially in the CA1 area of the hippocampus. This review summarizes the latest research linking ASIC1a to synaptic function either in physiological or pathological conditions.

Targeting Synaptic Plasticity in Experimental Models of Alzheimer's Disease.

Long-term potentiation (LTP) and long-term depression (LTD) of hippocampal synaptic transmission represent the principal experimental models underlying learning and memory. Alterations of synaptic plasticity are observed in several neurodegenerative disorders, including Alzheimer's disease (AD). Indeed, synaptic dysfunction is an early event in AD, making it an attractive therapeutic target for pharmaceutical intervention.

Acid-Sensing Ion Channel 1a Is Involved in N-Methyl D-Aspartate Receptor-Dependent Long-Term Depression in the Hippocampus.

Acid-sensing ion channels (ASICs), members of the degenerin/epithelial Na channel superfamily, are largely expressed in the mammalian nervous system. ASIC1a is highly permeable to Ca and are involved in many physiological processes, including synaptic plasticity, learning, and memory. To clarify the role of ASIC1a in synaptic transmission and plasticity, we investigated N-methyl D-aspartate (NMDA) receptor-dependent long-term depression (LTD) in the CA1 region of the hippocampus.

Lithium as a Treatment for Alzheimer's Disease: The Systems Pharmacology Perspective.

Systems pharmacology is a novel framework for drug research that models traditional and innovative pharmacological parameters and provides the overall efficacy and safety profile of a drug across body systems and complex, non-linear, molecular interactions. Lithium chloride, a pharmacological compound approved for the therapy of psychiatric disorders, represents a poorly explored compound for the treatment of Alzheimer's disease (AD). Lithium has been shown to reduce downstream effects associated with the aberrant overactivation of certain molecular pathways, such as glycogen synthase kinase 3 subunit β (GSK3-β)-related pathways, involved in AD-related pathophysiology.

The selective disruption of presynaptic JNK2/STX1a interaction reduces NMDA receptor-dependent glutamate release.

The neuronal loss caused by excessive glutamate release, or 'excitotoxicity', leads to several pathological conditions, including cerebral ischemia, epilepsy, and neurodegenerative diseases. Over-stimulation of presynaptic N-methyl-D-aspartate (NMDA) receptors is known to trigger and support glutamate spillover, while postsynaptic NMDA receptors are responsible for the subsequent apoptotic cascade. Almost all molecules developed so far are unable to selectively block presynaptic or postsynaptic NMDA receptors, therefore a deeper knowledge about intracellular NMDA pathways is required to design more specific inhibitors.

The positive allosteric modulator at mGlu2 receptors, LY487379, reverses the effects of chronic stress-induced behavioral maladaptation and synaptic dysfunction in the adulthood.

Chronic stress induces maladaptive neural responses in several brain areas including hippocampus. It has been demonstrated that chronic stress exposure induced a downregulation of the putative presynaptic type 2 metabotropic glutamate (mGlu2) receptors, which would reduce the negative feedback role exerted by these receptors. The reduced availability of these receptors would enhance glutamate overflow in the hippocampus, supporting the hypothesis that hippocampal glutamatergic neurotransmission plays a key etiopathological determinant in stress-induced neuropsychiatric disorders.

Stress as risk factor for Alzheimer's disease.

Prolonged stress predisposes susceptible individuals to a number of physiological disorders including cardiovascular disease, obesity and gastrointestinal disorders, as well as psychiatric and neurodegenerative disorders. Preclinical studies have suggested that manipulation of the glucocorticoid milieu can trigger cellular, molecular and behavioral derangement resembling the hallmarks of Alzheimer's Disease (AD). For example, stress or glucocorticoid administration can increase amyloid ß precursor protein and tau phosphorylation which are involved in synaptic dysfunction and neuronal death associated with AD.

Role of ASIC1a in Aβ-induced synaptic alterations in the hippocampus.

Acid-sensing ion channels (ASICs) are widely expressed in the mammalian central nervous system where they play a key role in synaptic transmission and in specific forms of memory. On the other hand, ASICs can be persistently active under pathological conditions contributing to neuronal damage in ischemic stroke, brain trauma, epilepsy and Parkinson's disease. However, to date no experimental evidence has linked ASICs to Alzheimer's disease (AD).

Early alteration of distribution and activity of hippocampal type-1 cannabinoid receptor in Alzheimer's disease-like mice overexpressing the human mutant amyloid precursor protein.

Besides its involvement in Alzheimer's disease (AD) as precursor of the neurotoxic amyloid peptides, the pathophysiological impact of brain accumulation of amyloid precursor protein (APP) is not yet well understood. Recent studies reported that APP interacts with other membrane proteins, including G protein coupled receptors, affecting their biological functions. Here, we focused on the study of the potential impact of human mutant APP on expression, distribution and activity of type-1 cannabinoid (CB) receptor in the hippocampus of Tg2576 mice, an AD-like mice model.

Neuregulin 1/ErbB signalling modulates hippocampal mGluRI-dependent LTD and object recognition memory.

The neurotrophic factors neuregulins (NRGs) and their receptors, ErbB tyrosine kinases, regulate neurotransmission, synaptic plasticity and cognitive functions and their alterations have been associated to different neuropsychiatric disorders. Group 1 metabotropic glutamate receptors (mGluRI)-dependent mechanisms are also altered in animal models of neuropsychiatric diseases, especially mGluRI-induced glutamatergic long-term depression (mGluRI-LTD), a form of synaptic plasticity critically involved in learning and memory. Despite this evidence, a potential link between NRGs/ErbB signalling and mGluRI-LTD has never been considered.

PDGF Modulates Synaptic Excitability and Short-Latency Afferent Inhibition in Multiple Sclerosis.

Maintenance of synaptic plasticity reserve is crucial to contrast clinical deterioration in MS and PDGF plays a key role in this phenomenon. Indeed, higher cerebrospinal fluid PDGF concentration correlates with improved clinical recovery after a relapse, and the amplitude of LTP-like cortical plasticity in relapsing-remitting MS patients. However, LTP-like cortical plasticity varies depending on the individual level of inhibitory cortical circuits.