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.

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.

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.

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.

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.

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.

Brain derived neurotrophic factor (BDNF) containing neurons in the hypothalamic paraventricular and supraoptic nuclei of juvenile and middle-aged rats after chronic stress.

The type and duration of stress stimulation are postulated to affect the expression of the brain derived neurotrophic factor (BDNF) differentially during ontogenetic life. The aim of our study was to investigate the influence of two different stressors, i.e.

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.

Effects of chronic forced swim stress on hippocampal brain-derived neutrophic factor (BDNF) and its receptor (TrkB) immunoreactive cells in juvenile and aged rats.

A type of stress stimulation and age are claimed to affect the expression of brain-derived neurotrophic factor (BDNF) and its receptor - tyrosine kinase B (TrkB) in the hippocampal regions differentially. This study aimed to explore the influence of chronic (15 min daily for 21 days) forced swim stress (FS) exposure on the BDNF and TrkB containing neurons in the hippocampal CA1, CA3 pyramidal cell layers and dentate gyrus (DG) granule cell layer in juvenile (P28) and aged (P360) rats. An immunofluorescence (-ir) method was used to detect BDNF-ir and TrkB-ir cells.

Changes in NGF/c-Fos double staining in the structures of the limbic system in juvenile and aged rats exposed to forced swim test.

This study aimed to investigate the influence of acute (a single 15 min) and chronic (15 min daily for 21 days) exposure to forced swim (FS) test on nerve growth factor (NGF)/c-Fos cells in hypothalamic paraventricular (PV) and supraoptic (SO) nuclei, the central (CeA) and medial (MeA) amygdaloid nuclei and CA3-hippocampus in juvenile (P28) and aged (P360) rats. The double-immunofluorescence (-ir) method was used to detect NGF-ir and c-Fos-ir cells. The amount of NGF/c-Fosir cells in relation to all NGF-ir cells is shown as a percentage.

The anatomical relationships between the serotonergic afferents and the neurons containing calcium-binding proteins in the rat claustrum.

Claustrum is a telencephalic structure integrating information of various modalities. Proper functioning of this structure depends on the presence of a network of intrinsic connections. This includes GABA-ergic neuronal populations that also contain calcium-binding proteins (CaBPs).

Fibroblast growth factor receptor signaling affects development and function of dopamine neurons - inhibition results in a schizophrenia-like syndrome in transgenic mice.

Developing and mature midbrain dopamine (DA) neurons express fibroblast growth factor (FGF) receptor-1 (FGFR1). To determine the role of FGFR1 signaling in the development of DA neurons, we generated transgenic mice expressing a dominant negative mutant [FGFR1(TK-)] from the catecholaminergic, neuron-specific tyrosine hydroxylase (TH) gene promoter. In homozygous th(tk-)/th(tk-) mice, significant reductions in the size of TH-immunoreactive neurons were found in the substantia nigra compacta (SNc) and the ventral tegmental area (VTA) at postnatal days 0 and 360.

Organically modified silica nanoparticles: a nonviral vector for in vivo gene delivery and expression in the brain.

This article reports on the application of organically modified silica (ORMOSIL) nanoparticles as a nonviral vector for efficient in vivo gene delivery. Highly monodispersed, stable aqueous suspension of nanoparticles, surface-functionalized with amino groups for binding of DNA, were prepared and characterized. Stereotaxic injections of nanoparticles, complexed with plasmid DNA encoding for EGFP, into the mouse ventral midbrain and into lateral ventricle, allowed us to fluorescently visualize the extensive transfection of neuronal-like cells in substantia nigra and areas surrounding the lateral ventricle.

Control of CREB-binding protein signaling by nuclear fibroblast growth factor receptor-1: a novel mechanism of gene regulation.

In integrative nuclear fibroblast growth factor receptor-1 (FGFR1) signaling a newly synthesized FGFR1 translocates to the nucleus to stimulate cell differentiation and associated gene activities. The present study shows that FGFR1 accumulates and interacts with the transcriptional co-activator CREB-binding protein (CBP) in nuclear speckle domains in the developing brain and in neural progenitor-like cells in vitro, which accompanies differentiation and postmitotic growth. Cell differentiation and gene activation by nuclear FGFR1 do not require tyrosine kinase activity.

Analysis of calretinin immunoreactivity in the rat piriform cortex after open field stress during postnatal maturation.

In our study we used c-Fos protein to identify whether cells containing calretinin (CR) in the rat piriform cortex are engaged in the response to stress stimulation and to find out how this expression changes during maturation (PC). The material consisted of Wistar strain rats of between 0 and 120 days of age divided into 9 groups. Each group consisted of 5 experimental and 3 control rats.