Pressure Cycling Technology Combined With MicroLC-SWATH Mass Spectrometry for the Analysis of Sex-Related Differences Between Male and Female Cerebella: A Promising Approach to Investigating Proteomics Differences in Psychiatric and Neurodegenerative Diseases.

Purpose: Pressure cycling technology (PCT) coupled with data-independent sequential window acquisition of all theoretical mass spectra (SWATH-MS) can be a powerful tool for identifying and quantifying biomarkers (e.g., proteins) in complex biological samples.

The cerebellum: the 'little' brain and its big role.

Reports from recent years provide compelling evidence about the structure and the existence of functional topography in the cerebellum. However, most of them focused on the motor functions of the cerebellum. Recent studies suggest the involvement of the posterior lobe of the cerebellum in the context of neurodegenerative and cognitive disorders.

Monitoring of age- and gender-related alterations of endocannabinoid levels in selected brain regions with the use of SPME probes.

Introduction: The endocannabinoid system consists of different types of receptors, enzymes and endocannabinoids (ECs), which are involved in several physiological processes, but also play important role in the development and progression of central nervous system disorders.

Objectives: The purpose of this study was to apply precise and sensitive methodology for monitoring of four ECs, namely anandamide (AEA), 2-arachidonoyl glycerol (2-AG), N-arachidonoyl dopamine (NADA), 2-arachidonyl glyceryl ether (2-AGe) in selected brain regions of female and male rats at different stages of development (young, adult and old).

Methods: Biocompatible solid-phase microextraction (SPME) probes were introduced into the intact (non-homogenized) brain structures for isolation of four ECs, and the extracts were subjected to LC-MS/MS analysis.

How to write an umbrella review? A step-by-step tutorial with tips and tricks.

The number of meta-analyses (MA) and systematic reviews (SR) on various medical issues has increased during the last two decades. The MA and SR results may differ from one another due to a number of factors such as inaccurate or diverse searches through the databases, discrepancies in the extraction process or in statistical analysis, among others. Some results may even contradict one another, resulting in confusion among readers.

Mechanoreceptor Piezo1 Is Downregulated in Multiple Sclerosis Brain and Is Involved in the Maturation and Migration of Oligodendrocytes .

Mechanical properties of the brain such as intracranial pressure or stiffness of the matrix play an important role in the brain's normal physiology and pathophysiology. The physical properties are sensed by the cells through mechanoreceptors and translated into ion currents which activate multiple biochemical cascades allowing the cells to adapt and respond to changes in their microenvironment. Piezo1 is one of the first identified mechanoreceptors.

Can the kisspeptin help us in the understanding of pathology of some neurodegenerative brain diseases?

It is already known that the discovery of kisspeptin was a revolutionary step in the understanding of neuroendocrine regulation of reproduction. Kisspeptin is one of the main moderators of the gonadotropic axis, but the kisspeptin gene is known to be expressed in various regions of the central nervous system. The activity of kisspeptin is not limited to hypothalamic pituitary gonadal axis; it participates in the regulation of multiple neuronal circuits in the limbic system.

EBI2 is expressed in glial cells in multiple sclerosis lesions, and its knock-out modulates remyelination in the cuprizone model.

EBI2 receptor regulates the immune system, and in multiple, sclerosis is upregulated in the central nervous system infiltrating lymphocytes. In newborn EBI2-deficient mice, myelin development is delayed, and its persistent antagonism inhibits remyelination in chemically demyelinated organotypic cerebellar slices. We used the cuprizone model of multiple sclerosis to elucidate the role of central nervous system-expressed EBI2 in de- and remyelination.

EBI2 Is Temporarily Upregulated in MO3.13 Oligodendrocytes during Maturation and Regulates Remyelination in the Organotypic Cerebellar Slice Model.

The EBI2 receptor regulates the immune system and is expressed in various immune cells including B and T lymphocytes. It is also expressed in astrocytes in the central nervous system (CNS) where it regulates pro-inflammatory cytokine release, cell migration and protects from chemically induced demyelination. Its signaling and expression are implicated in various diseases including multiple sclerosis, where its expression is increased in infiltrating immune cells in the white matter lesions.

Phenylbutyrate administration reduces changes in the cerebellar Purkinje cells population in PDC‑deficient mice.

In humans, pyruvate dehydrogenase complex (PDC) deficiency impairs brain energy metabolism by reducing the availability of the functional acetyl‑CoA pool. This "hypometabolic defect" results in congenital lactic acidosis and abnormalities of brain morphology and function, ranging from mild ataxia to profound psychomotor retardation. Our previous study showed reduction in total cell number and dendritic arbors in the cerebellar Purkinje cells in systemic PDC‑deficient mice.

Pyruvate dehydrogenase deficiency: morphological and metabolic effects, creation of animal model to search for curative treatment.

The main source of energy for brain and other organs is glucose. To obtain energy for all tissue, glucose has to come through glycolysis; then as pyruvate it is converted to acetyl-CoA by pyruvate dehydrogenase complex (PDC) and finally enters citric acid cycle. What happens when one of these stages become disturb? Mutation in genes encoding subunits of PDC leads to pyruvate dehydrogenase deficiency.

The influence of early postnatal chronic mild stress stimulation on the activation of amygdala in adult rat.

Amygdala is a limbic structure involved in the stress response. The immunohistochemical and morphometric methods were used to examine whether the chronic mild psychological stress during the early postnatal period would change activation of amygdaloid nuclei in response to the same stressor in adult. In the study we focused on the role of neurons containing calbindin (CB), calretinin (CR), parvalbumin (PV) and nitric oxide synthase (NOS).

Effects of Inducing Gamma Oscillations in Hippocampal Subregions DG, CA3, and CA1 on the Potential Alleviation of Alzheimer's Disease-Related Pathology: Computer Modeling and Simulations.

The aim of this study was to evaluate the possibility of the gamma oscillation function (40-130 Hz) to reduce Alzheimer's disease related pathology in a computer model of the hippocampal network dentate gyrus, CA3, and CA1 (DG-CA3-CA1) regions. : Computer simulations were made for a pathological model in which Alzheimer's disease was simulated by synaptic degradation in the hippocampus. Pathology modeling was based on sequentially turning off the connections with entorhinal cortex layer 2 (EC2) and the dentate gyrus on CA3 pyramidal neurons.

Computer Modeling of Alzheimer's Disease-Simulations of Synaptic Plasticity and Memory in the CA3-CA1 Hippocampal Formation Microcircuit.

This paper aims to present computer modeling of synaptic plasticity and memory in the CA3-CA1 hippocampal formation microcircuit. The computer simulations showed a comparison of a pathological model in which Alzheimer's disease (AD) was simulated by synaptic degradation in the hippocampus and control model (healthy) of CA3-CA1 networks with modification of weights for the memory. There were statistically higher spike values of both CA1 and CA3 pyramidal cells in the control model than in the pathological model (p = 0.

Synthesis and Biological Evaluation of Acridine/Acridone Analogs as Potential Anticancer Agents.

Background: The lack of efficacious therapy for advanced melanoma and neuroblastoma makes new approaches necessary. Therefore, many scientists seek new, more effective, more selective and less toxic anticancer drugs.

Objective: We propose the synthesis of the new functionalized analogs of 1-nitroacridine/4- nitroacridone connected to tuftsin/retro-tuftsin derivatives as potential anticancer agents.

Brain Organoids: Expanding Our Understanding of Human Development and Disease.

Stem cell-derived brain organoids replicate important stages of the prenatal human brain development and combined with the induced pluripotent stem cell (iPSC) technology offer an unprecedented model for investigating human neurological diseases including autism and microcephaly. We describe the history and birth of organoids and their application, focusing on cerebral organoids derived from embryonic stem cells and iPSCs. We discuss new insights into organoid-based model of schizophrenia and shed light on challenges and future applications of organoid-based disease model system.

Organisation of the dopamine neuronal subsets within midbrain of the feathertail glider (Acrobates pygmaeus, Acrobatidae, Marsupialia).

The Marsupial feathertail glider has a unique set of morphological, anatomical and behavioural features that make it a promising model for study of primate evolution. Among them it has many locomotor adaptations to arboreal life, such as diagonal gait of movements, gliding, fast climbing and running along branches. These ecological and behavioural specialisations could result in differences in anatomy of the brain systems involved in their integration.

Correlation between dopaminergic phenotype and expression of calretinin in the midbrain nuclei of the opossum (Monodelphis domestica): an immunohistological study.

We investigated distribution and morphology of neurons of the midbrain nuclei: the ventral tegmental area (VTA), substantia nigra (SN) and periaqueductal gray (PAG) of the adult grey short-tailed opossums that were double immunolabeled for the presence of calretinin (CR) and/or tyrosine hydroxylase (TH). The majority of TH-immunopositive neurons and fibers were located in the VTA, SN, and only scarce population of small neurons expressing TH was present in the PAG. In the SN 80 percent of TH-expressing neurons had large cell bodies, and only a small fraction had small perikarya.

Effect of light-dark changes on the locomotor activity in open field in adult rats and opossums.

There have been no reports on how the light-dark changes determine the locomotor activity of animals in the group of high reactivity (HR) and low reactivity (LR). In the present study we have compared selected parameters of the locomotor activity of the HR and the LR groups of the laboratory opossums and Wistar rats during consecutive, light and dark phases in the open field test. Sixty male Wistar adult rats, at an average weight of 350 g each, and 24 adult Monodelphis opossums of both sexes at an average weight of 120 g each were used.

Transcription factor Pax6 is expressed by astroglia after transient brain ischemia in the rat model.

Reactive astrogliosis is regarded as an universal astrocytic response to different kinds of lesions, concerned with glial fibrillary acidic protein (GFAP) up-regulation, cellular hypertrophy and proliferation. The origin of reactive and proliferating cells in the adult brain is still disputable. Persistent progenitors as well as de-differentiating adult cells of various glial lineages are regarded as possible candidates.

Activation of developmental nuclear fibroblast growth factor receptor 1 signaling and neurogenesis in adult brain by α7 nicotinic receptor agonist.

Reactivation of endogenous neurogenesis in the adult brain or spinal cord holds the key for treatment of central nervous system injuries and neurodegenerative disorders, which are major health care issues for the world's aging population. We have previously shown that activation of developmental integrative nuclear fibroblast growth factor receptor 1 (FGFR1) signaling (INFS), via gene transfection, reactivates neurogenesis in the adult brain by promoting neuronal differentiation of brain neural stem/progenitor cells (NS/PCs). In the present study, we report that targeting the α7 nicotinic acetylcholine receptors (α7nAChRs) with a specific TC-7020 agonist led to a robust accumulation of endogenous FGFR1 in the cell nucleus.

α7 nicotinic receptor agonist reactivates neurogenesis in adult brain.

Reactivation of neurogenesis by endogenous Neural Stem/Progenitor Cells (NS/PC) in the adult brain or spinal cord holds the key for treatment of CNS injuries as well as neurodegenerative disorders, which are major healthcare issues for the world's aging population. Recent studies show that targeting the α7 nicotinic acetylcholine receptors (α7nAChR) with a specific TC-7020 agonist inhibits proliferation and stimulates neuronal differentiation of NS/PC in subventricular zone (SVZ) in the adult mouse brain. TC-7020-induced neuronogenesis is observed in different brain regions, including: (1) βIII Tubulin-expressing cortical neurons, (2) calretinin expressing hippocampal neurons and (3) cells in substantia nigra (SN) expressing predopaminergic Nurr1+phenotype.

Different strategies of exploration and phenotypic variability of the locomotor behavior in new environment: Comparative study of the laboratory opossum (Monodelphis domestica) and Wistar rat (Rattus norvegicus).

Spontaneous locomotor activity of opossums and Wistar rats during a two-hour session in the open field has been recorded, assessed and behavior of individuals of the two species compared. Afterwards, groups of highly active (HA) and low active (LA) opossums and rats were selected on the basis of the distance traveled in the test. Differences between the selected groups were evaluated.

Schizophrenia: a neurodevelopmental disorder--integrative genomic hypothesis and therapeutic implications from a transgenic mouse model.

Schizophrenia is a neurodevelopmental disorder featuring complex aberrations in the structure, wiring, and chemistry of multiple neuronal systems. The abnormal developmental trajectory of the brain appears to be established during gestation, long before clinical symptoms of the disease appear in early adult life. Many genes are associated with schizophrenia, however, altered expression of no one gene has been shown to be present in a majority of schizophrenia patients.

Nerve growth factor (NGF) immunoreactive neurons in the juvenile rat hippocampus: response to acute and long-term high-light open-field (HL-OF) or forced swim (FS) stress stimulation.

This study aimed at examining and comparing the influence of two different stress stimuli on the density (number of cells/mm²) of nerve growth factor (NGF) containing neurons in the hippocampal CA1 and CA3 pyramidal cell layers and the dentate gyrus (DG) granule cell layer in juvenile rats (P28; P-postnatal day). The high-light open-field (HL-OF) test and forced swim (FS) test were employed to investigate the effects of a single, 15-min acute exposure and repeated (15 min daily for 21 days) long-term exposure to stress. In order to detect NGF-ir neurons, immunohistochemical (-ir) techniques were used.

Do two models of acute and chronic stress stimulation influence the amount of nerve growth factor (NGF) and its receptor TrkA in the hippocampal neurons of middle aged rats?

Our study aimed to explore the influence of two different stressors: acute (once for 15 min) and chronic (15 min daily for 21 days) exposure to high light open field (HL-OF) or forced swim (FS) on the density of nerve growth factor (NGF) and tyrosine kinase A (TrkA) immunoreactive neurons in the hippocampal CA1 and CA3 pyramidal cell layers and dentate gyrus (DG) granule cell layer in middle aged (360 days old; P360; P, postnatal day) rats. In contrast to non-stressed animals, acute HL-OF stimulation resulted in an increase (p<0.001) in the density of NGF-ir cells in CA1, CA3, DG, whereas chronic HL-OF produced no changes in all hippocampal regions.