Wprowadzenie

Oddajemy w ręce Czytelników kolejny tom czasopisma „Rozwój Regionalny i Polityka Regionalna”, który jest efektem obrad cyklicznej konferencji naukowej Forum Architektury Krajobrazu. Tytuł tegorocznego XXIV spotkania brzmiał „Architektura krajobrazu wobec zagrożeń współczesności”. Konferencja odbywała się zdalnie w dniach 1–2 grudnia 2022 r. i była współorganizowana przez Wydział Rolnictwa, Ogrodnictwa i Bioinżynierii Uniwersytetu Przyrodniczego w Poznaniu oraz Wydział Geografii Społeczno-Ekonomicznej i Gospodarki Przestrzennej Uniwersytetu im. Adama Mickiewicza w Poznaniu

P2X7 Receptor is Involved in Mitochondrial Dysfunction Induced by Extracellular Alpha Synuclein in Neuroblastoma SH-SY5Y Cells

The purinergic P2X7 receptor (P2X7R) belongs to a family of trimeric ion channels that are gated by extracellular adenosine 5′-triphosphate (ATP). Several studies have pointed to a role of P2X7R-dependent signalling in Parkinson\u27s disease (PD)-related neurodegeneration. The pathology of (PD) is characterized by the formation of insoluble alpha-synuclein (α-Syn) aggregates—Lewy bodies, but the mechanisms underlying α-Syn-induced dopaminergic cell death are still partially unclear. Our previous studies indicate that extracellular α-Syn directly interact with neuronal P2X7R and induces intracellular free calcium mobilization in neuronal cells. The main objective of this study was to examine the involvement of P2X7R receptor in α-Syn-induced mitochondrial dysfunction and cell death. We found that P2X7R stimulation is responsible for α-Syn-induced oxidative stress and activation of the molecular pathways of programmed cell death. Exogenous α-Syn treatment led to P2X7R-dependent decrease in mitochondrial membrane potential as well as elevation of mitochondrial ROS production resulting in breakdown of cellular energy production. Moreover, P2X7R-dependent deregulation of AMP-activated protein kinase as well as decrease in parkin protein level could be responsible for α-Syn-induced mitophagy impairment and accumulation of dysfunctional mitochondria. P2X7R might be putative pharmacological targets in molecular mechanism of extracellular α-Syn toxicity

Prenatal exposure to valproic acid induces alterations in the expression and activity of purinergic receptors in the embryonic rat brain

Purinergic signalling is involved in the control of several processes related to brain development, such as neurogenesis and gliogenesis, migration and differentiation of neuronal precursors, synaptogenesis and synaptic elimination to achieve a fully wired and efficient mature brain. Therefore, any deregulation of purine-dependent signalling mediated by stimulation of specific adenosine and purinergic receptor subtypes: P1, P2X, or P2Y, can lead to functional deficits and the development of neuropsychiatric disorders, including autism spectrum disorders (ASD). In this study, we investigated the changes in expression and activity of selected purinergic receptors during rat brain development in an animal model of ASD. Pregnant dams received an intraperitoneal injection of valproic acid (VPA; 450 mg/kg body weight) at embryonic day (ED) 12.5, around the time of neural tube closure. Subsequently, changes in the expression and activity of specific purinergic receptor subtypes were analysed at ED19, an important prenatal stage of brain development. Our results suggest that prenatal VPA exposure leads to a significant increase in the level and activity of adenosinergic receptors A1, A2b and A3, which are involved in the regulation of progenitor cell proliferation and nerve growth, and upregulation of purinergic P2X2/P2X3 receptors, which in turn may contribute to the postnatal neuroanatomical abnormalities and synaptic dysfunction. Conversely, the significant downregulation of P2Y1 and P2X7 receptors, together with their reduced activity in the embryonic VPA brain, may indicate disturbances in the processes of neuronal precursor migration and differentiation, dendritic and axonal formation, and glutamate/GABA imbalance, thereby altering neuronal excitability. In conclusion, defects in purinergic signalling induced by prenatal VPA exposure could have a profound impact on brain development during embryogenesis and on intellectual and behavioural functions after birth. These observations could provide clues for future implementation of potential therapeutic strategies for ASD

Glia-Neurotrophic Factor Relationships: Possible Role in Pathobiology of Neuroinflammation-Related Brain Disorders

Neurotrophic factors (NTFs) play an important role in maintaining homeostasis of the central nervous system (CNS) by regulating the survival, differentiation, maturation, and development of neurons and by participating in the regeneration of damaged tissues. Disturbances in the level and functioning of NTFs can lead to many diseases of the nervous system, including degenerative diseases, mental diseases, and neurodevelopmental disorders. Each CNS disease is characterized by a unique pathomechanism, however, the involvement of certain processes in its etiology is common, such as neuroinflammation, dysregulation of NTFs levels, or mitochondrial dysfunction. It has been shown that NTFs can control the activation of glial cells by directing them toward a neuroprotective and anti-inflammatory phenotype and activating signaling pathways responsible for neuronal survival. In this review, our goal is to outline the current state of knowledge about the processes affected by NTFs, the crosstalk between NTFs, mitochondria, and the nervous and immune systems, leading to the inhibition of neuroinflammation and oxidative stress, and thus the inhibition of the development and progression of CNS disorders

The Role of Bromodomain and Extraterminal (BET) Proteins in Controlling the Phagocytic Activity of Microglia In Vitro: Relevance to Alzheimer’s Disease

The correct phagocytic activity of microglia is a prerequisite for maintaining homeostasis in the brain. In the analysis of mechanisms regulating microglial phagocytosis, we focused on the bromodomain and extraterminal domain (BET) proteins: Brd2, Brd3, and Brd4, the acetylation code readers that control gene expression in cooperation with transcription factors. We used pharmacological (JQ1) and genetic (siRNA) inhibition of BET proteins in murine microglial cell line BV2. Inhibition of BET proteins reduced the phagocytic activity of BV2, as determined by using a fluorescent microspheres-based assay and fluorescently labelled amyloid-beta peptides. Gene silencing experiments demonstrated that all brain-existing BET isoforms control phagocytosis in microglia. From a set of 84 phagocytosis-related genes, we have found the attenuation of the expression of 14: Siglec1, Sirpb1a, Cd36, Clec7a, Itgam, Tlr3, Fcgr1, Cd14, Marco, Pld1, Fcgr2b, Anxa1, Tnf, Nod1, upon BET inhibition. Further analysis of the mRNA level of other phagocytosis-related genes which were involved in the pathomechanism of Alzheimer’s disease demonstrated that JQ1 significantly reduced the expression of Cd33, Trem2, and Zyx. Our results indicate the important role of BET proteins in controlling microglial phagocytosis; therefore, targeting BET may be the efficient method of modulating microglial activity