Marco Sassoè-Pognetto

• Professor (Associate) at University of Turin

Background Choroid plexus (ChP) is the secretory epithelial structure located in brain ventricles. Choroid plexus tumors (CPTs) are rare neoplasms predominantly occurring in young patients with intensified malignancy in children. CPT treatment is hindered by insufficient knowledge of the tumor pathology and limited availability of valid models. Me...

Fibrosis is a marker of chronic kidney disease (CKD) and consists of the accumulation of the extracellular matrix (ECM) components, causing the progressive deterioration of kidney function. Human liver stem cells (HLSCs) have anti-fibrotic activity, and HLSC-derived extracellular vesicles (EVs) mediate this effect. Herein, we evaluated the ability...

Background Bites caused by European vipers are rare medical emergencies but can occasionally cause life-threatening complications. Viper venom causes local symptoms, which can be accompanied by systemic manifestations in severe cases. The local effects of snakebites include edema and, more rarely, necrosis and compartment syndrome. The consequences...

These are the "proceedings" of the SHI scientific congress held in Turin in September 2022. It is a compilation of 21 papers dealing with several aspects of amphibian and reptile biology. Further and separate articles will be shared on Research Gate as well. Those interested in receiving more information could contact the editors.

A chiusura del volume degli atti del XIV Congresso Nazionale della Societas Herpetologica Italica, tenutosi a Torino dal 13 al 17 settembre 2022, vengono celebrati due erpetologi piemontesi di spicco in occasione del bicentenario della nascita di Michele Lessona (1823-1894) e del centenario della scomparsa di Mario Giacinto Peracca (1861-1923).

This report describes three cases of human envenomation by the asp viper (Vipera aspis) in Piedmont, north-west Italy. A woman was bitten on the ankle while she was hiking and two herpetologists received bites on the hand while they were manipulating the animals. In the first case, the victim presented severe systemic symptoms (abdominal pain, vomi...

Due to its stereotyped cellular architecture, the cerebellum has always constituted a useful model system for studying the basic organization and development of synaptic circuits. This chapter describes the current state of knowledge relating to the development of cerebellar glutamate and GABA synapses and highlights observations on the molecular a...

Background Choroid plexuses (ChPs) are intraventricular structures mainly composed by specialized epithelial cells interconnected by tight junctions that establish the blood-cerebrospinal fluid (CSF) barrier. ChPs are essential to produce CSF and transport solutes from and into the brain. Deterioration of ChP function and morphology has been correl...

Choroid plexus (ChP) epithelium is composed of specialized multiciliated cells. By using multiple microscopic techniques, biochemical approaches in various mutant mice and longitudinal analysis from mouse embryogenesis to aging, we show that ChP cilia are built on a gradient of events which are spatio-temporally regulated. We uncover that ChP cilia...

Ecology and abundance of the Walser viper In the period 2016-2019, we performed repeated surveys of 67 study sites placed within the Walser viper known distribution range, collecting 55 occurrence data. We combined field observations with 59 bibliographic records, in order to gather an exhaustive dataset of the viper occurrences. Employing the alph...

The abstract book of the XIV herpetological congress of the Societas Herpetologica Italica (SHI), with plenary lectures, ordinary talks and poster presentations.

Neuroligin-3 is a postsynaptic adhesion molecule involved in development, function, and pathologies of synapses in the brain. It is a genetic cause of autism and a potent component of the tumor microenvironment in gliomas. There are four Neuroligins that operate at distinct synapse types, selectively interacting with presynaptic adhesion and postsy...

In this study, we investigated the use of wireless ultrasonography as an imaging system to study the reproductive ecology of the asp viper (Vipera aspis), a viviparous snake found in southwestern Europe. Female vipers were captured during the summer and immediately scanned to obtain an estimate of the number of embryos. Ultrasound imaging was perfo...

Growing evidence demonstrates that serotonin (5-HT) depletion increases activity in the amygdala and medial prefrontal cortex (mPFC), ultimately leading to anxiety behavior. Previously, we showed that glyphosate-based herbicides (GBHs) increased anxiety levels and reduced the number of serotoninergic fibers within the mPFCs and amygdalas of exposed...

Despite Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) -induced Oxidative Stress (OxS) being well documented in different organs, the molecular pathways underlying placental OxS in late-pregnancy women with SARS-COV-2 infection are poorly understood. Herein, we performed an observational study to determine whether placentae of women t...

RIASSUNTO In questo lavoro viene presa in esame la presenza della rana toro (Lithobates catesbeianus Shaw, 1802) nelle collezio-ni museali italiane. Viene riportata la presenza di questo anfibio in numerose collezioni museali, sia nei grandi musei metropolitani, sia in alcuni musei provinciali di minori dimensioni. La presenza della rana toro nei m...

Human liver stem-cell-derived extracellular vesicles (HLSC-EVs) exhibit therapeutic properties in various pre-clinical models of kidney injury. We previously reported an overall improvement in kidney function following treatment with HLSC-EVs in a model of aristolochic acid nephropathy (AAN). Here, we provide evidence that HLSC-EVs exert anti-fibro...

In the rodent olfactory bulb the smooth dendrites of the principal glutamatergic mitral cells (MCs) form reciprocal dendrodendritic synapses with large spines on GABAergic granule cells (GC), where unitary release of glutamate can trigger postsynaptic local activation of voltage-gated Na ⁺ -channels (Na v s), that is a spine spike. Can such single...

Multiple myeloma is a plasma cell neoplasm characterized by the production of unfolded immunoglobulins, which cause endoplasmic reticulum (ER) stress and sensitivity to proteasome inhibition. The genomic landscape of multiple myeloma is characterized by the loss of several genes rarely mutated in other cancers that may underline specific weaknesses...

Muscle dystrophin–glycoprotein complex (DGC) links the intracellular cytoskeleton to the extracellular matrix. In neurons, dystroglycan and dystrophin, two major components of the DGC, localize in a subset of GABAergic synapses, where their function is unclear. Here we used mouse models to analyze the specific role of the DGC in the organization an...

Glyphosate-based herbicides (GBH) are the most widely used pesticides worldwide. Despite considerable progress in describing the neurotoxic potential of GBH, the harmful effects on brain cytoarchitecture and behavior are still unclear. Here, we addressed the developmental impact of GBH by exposing female mice to 250 or 500 mg/kg doses of GBH during...

published on BioRxiv, doi.org/10.1101/440198 I do not know why Researchgate seems to be "unwilling" to update the previous version. I cannot enter the correct DOI for unknown reasons.

Mutations in the CDKL5 (cyclin-dependent kinase-like 5) gene cause CDKL5 Deficiency Disorder (CDD), a severe neurodevelopmental syndrome where patients exhibit early-onset seizures, intellectual disability, stereotypies, limited or absent speech, autism-like symptoms and sensory impairments. Mounting evidences indicate that disrupted sensory percep...

Key points Tymothy syndrome (TS) is a multisystem disorder featuring cardiac arrhythmias, autism and adrenal gland dysfunction that originates from a de novo point mutation in the gene encoding the Cav1.2 (CACNA1C) L‐type channel. To study the role of Cav1.2 channel signals in autism, the autistic TS2‐neo mouse has been generated bearing the G406R...

Mitochondrial dysregulation plays a central role in cancers and drives reactive oxygen species (ROS)-dependent tumor progression. We investigated the pro-tumoral roles of mitochondrial dynamics and altered intracellular ROS levels in pancreatic ductal adenocarcinoma (PDAC). We identified ‘family with sequence similarity 49 member B’ (FAM49B) as a m...

The neuronal scaffold protein p140Cap was investigated during hippocampal network formation. p140Cap is present in presynaptic GABAergic terminals and its genetic depletion results in a marked alteration of inhibitory synaptic activity. p140Cap-/- cultured neurons display higher frequency of miniature inhibitory postsynaptic currents (mIPSCs) with...

Sab (SH3 binding protein 5 or SH3BP5) is a mitochondrial scaffold protein involved in signaling associated with mitochondrial dysfunction and apoptosis; furthermore, Sab is a crucial signaling platform for neurodegenerative disease. To determine how this signaling nexus could have a significant effect on disease, we examined the regional abundance...

Cyclin-dependent kinase-like 5 (CDKL5) mutations are found in severe neurodevelopmental disorders, including the Hanefeld variant of Rett syndrome (RTT; CDKL5 disorder). CDKL5 loss-of-function murine models recapitulate pathological signs of the human disease, such as visual attention deficits and reduced visual acuity. Here we investigated the cel...

Due to its stereotyped cellular architecture, the cerebellum has always constituted a useful model system for studying the basic organization and development of synaptic circuits. This chapter describes the current state of knowledge relating to the development of cerebellar glutamate and GABA synapses and reviews recent studies on the molecular an...

Since the groundbreaking work of Ramon y Cajal, the cerebellar Purkinje cell has always represented an ideal model for studying the organization, development and function of synaptic circuits. Purkinje cells receive distinct types of glutamatergic and GABAergic synapses, each characterized by exquisite sub-cellular and molecular specificity. The fo...

Actin is a regulator of synaptic vesicle mobilization and exocytosis, but little is known about the mechanisms that regulate actin at presynaptic terminals. Genetic data on LIMK1, a negative regulator of actin-depolymerizing proteins of the ADF/cofilin family, suggest a role for ADF/cofilin in presynaptic function. However, synapse physiology is fu...

Background Actin depolymerizing proteins of the ADF/cofilin family are essential for actin dynamics, which is critical for synaptic function. Two ADF/cofilin family members, namely ADF and n-cofilin, are highly abundant in the brain where they are present in excitatory synapses. Previous studies demonstrated the relevance of n-cofilin for postsynap...

Understanding the role of lipids in synapses and the aberrant molecular mechanisms causing the cognitive deficits that characterize most lipidosis is necessary to develop therapies for these diseases. Here we describe sphingomyelin (SM) as a key modulator of the dendritic spine actin cytoskeleton. We show that increased SM levels in neurons of acid...

Neurexins (Nrxs) have emerged as potential determinants of synaptic specificity, but little is known about their localization at central synapses. Here we show that Nrxs have a remarkably selective localization at distinct types of glutamatergic synapses and we reveal an unexpected ontogenetic regulation of Nrx expression at GABAergic synapses. Our...

The neurotransmitter GABA regulates many aspects of inhibitory synapse development. We tested the hypothesis that GABA receptors (GABARs) work together with the synaptic adhesion molecule neuroligin 2 (NL2) to regulate synapse formation in different subcellular compartments. We investigated mice ("γ2 knockdown mice") with an engineered allele of th...

Epigenetic changes such as covalent modifications of histone proteins represent complex molecular signatures that provide a cellular memory of previously experienced stimuli without irreversible changes of the genetic code. In this study we show that new gene expression induced in vivo by morphine withdrawal occurs with concomitant epigenetic modif...

More than a century ago, Ramón y Cajal based on the cerebellum his initial description of neurons labeled with the silver impregnation method, obtaining evidence in favor of the neuron doctrine. It is perhaps less known that Cajal also made an accurate description of cerebellar development, laying the foundation for successive studies of cell migra...

The ventral tegmental area (VTA) is widely implicated in drug addiction and other psychiatric disorders. This brain region is densely populated by dopaminergic (DA) neurons and also contains a sparse population of γ-aminobutyric acid (GABA)ergic cells that regulate the activity of the principal neurons. Therefore, an in-depth knowledge of the organ...

In mammals, olfactory bulb granule cells (GCs) are generated throughout life in the subventricular zone. GABAergic inputs onto newborn neurons likely regulate their maturation, but the details of this process remain still elusive. Here, we investigated the differentiation, synaptic integration, and survival of adult-born GCs when their afferent GAB...

The deregulation of brain cholesterol metabolism is typical in acute neuronal injury (such as stroke, brain trauma and epileptic seizures) and chronic neurodegenerative diseases (Alzheimer's disease). Since both conditions are characterized by excessive stimulation of glutamate receptors, we have here investigated to which extent excitatory neurotr...

Profilins are important regulators of actin dynamics and have been implicated in activity-dependent morphological changes of dendritic spines and synaptic plasticity. Recently, defective presynaptic excitability and neurotransmitter release of glutamatergic synapses were described for profilin2-deficient mice. Both dendritic spine morphology and sy...

Collybistin is a brain-specific guanine nucleotide exchange factor (GEF) that is crucial for the postsynaptic accumulation of gephyrin and γ-aminobutyric acid A receptors (GABA(A) Rs) at a specific subset of inhibitory synapses. Our understanding of the in vivo function of collybistin has been hampered by lack of information about the synaptic loca...

Actin plays important roles in a number of synaptic processes, including synaptic vesicle organization and exocytosis, mobility of postsynaptic receptors, and synaptic plasticity. However, little is known about the mechanisms that control actin at synapses. Actin dynamics crucially depend on LIM kinase 1 (LIMK1) that controls the activity of the ac...

GABAergic synapses exhibit a high degree of subcellular and molecular specialization, which contrasts with their apparent simplicity in ultrastructural appearance. Indeed, when observed in the electron microscope, GABAergic synapses fit in the symmetric, or Gray's type II category, being characterized by a relatively simple postsynaptic specializat...

The olfactory bulb (OB) receives and integrates newborn interneurons throughout life. This process is important for the proper functioning of the OB circuit and consequently, for the sense of smell. Although we know how these new interneurons are produced, the way in which they integrate into the pre-existing ongoing circuits remains poorly documen...

Supplementary Figure 2: Proximal synaptic responses evoked by minimal stimulation. Gradually increasing stimulus intensity abruptly evoked events in an all-or-none manner. Open and closed circles indicate response success and failure, respectively. Unitary response amplitude was confirmed to be constant by a small increase in the stimulus intensity...

Supplementary Figure 1: Classification of developing adult-generated granule cells (GCs). (A) Relationship between length of apical dendrite and maximal Na+ current evoked by a depolarizing step pulse. Adult-born GCs were classified according to Na+ current amplitude, with white, gray and black circles representing classes 3, 4 and 5, respectively....

Supplementary Figure 3: Developmental change of 3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated outward currents at depolarized membrane potentials. (A) Typical traces. After AMPAR-mediated and N-methyl D-aspartate receptor (NMDAR)-mediated currents were recorded at the holding potential of +40 mV, 2,3-dioxo-6-nitro-1,2,3,4-t...

Supplementary Figure 4: Ca2+-permeable AMPARs in class 3 GCs. (A) (Black) AMPAR-mediated EPSCs at the holding potential of -70 mV (red). This trace shows predicted data, obtained by inversion of the trace shown in black and multiplication by four-sevenths. (B) (Green) AMPAR-mediated and NMDAR-mediated EPSCs at the holding potential of +40 mV. (Pink...

Supplementary Figure 5: Axon terminals make contacts with both adult-born and pre-existing GCs. A large axon terminal (Ax: red) makes two synapses with a GFP-positive dendrite (GC at 7 days post-injection: green) and a GFP-negative dendrite (a presumptive pre-existing GC: blue). Arrows point to the postsynaptic density. Note that the synapse onto t...

Neuroligins (NL1-NL4) are postsynaptic adhesion proteins that control the maturation and function of synapses in the central nervous system (CNS). Loss-of-function mutations in NL4 are linked to rare forms of monogenic heritable autism, but its localization and function are unknown. Using the retina as a model system, we show that NL4 is preferenti...

In 1875 Camillo Golgi published his classical description of the olfactory bulb, which contained the first images of neurons visualized with the "black reaction". This new staining method opened the way for structural investigations of the nervous tissue, that culminated in the extraordinary neuroanatomical work of Ramón y Cajal and the formulation...

The third paper by Camillo Golgi on his new method was on the olfactory bulb. This paper has never been translated into English, but is of special interest both for its pioneering description of olfactory bulb cells and for containing the first illustration by Golgi of cells stained with his new method. A translation into English is provided in thi...

Gephyrin and collybistin are key components of GABAA receptor (GABAAR) clustering. Nonetheless, resolving the molecular interactions between the plethora of GABAAR subunits and these clustering proteins is a significant challenge. We report a direct interaction of GABAAR α2 and α3 subunit intracellular M3–M4 domain (but not α1, α4, α5, α6, β1–3, or...

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In the cerebellar cortex, interneurons of the molecular layer (stellate and basket cells) provide GABAergic input to Purkinje cells, as well as to each other and possibly to other interneurons. GABAergic inhibition in the molecular layer has mainly been investigated at the interneuron to Purkinje cell synapse. In this study, we used complementary s...

Neuronal plasticity is an important process for learning, memory and complex behaviour. Rapid remodelling of the actin cytoskeleton in the postsynaptic compartment is thought to have an important function for synaptic plasticity. However, the actin-binding proteins involved and the molecular mechanisms that in vivo link actin dynamics to postsynapt...

New olfactory bulb granule cells (GCs) are GABAergic interneurons continuously arising from neuronal progenitors and integrating into preexisting bulbar circuits. They receive both GABAergic and glutamatergic synaptic inputs from olfactory bulb intrinsic neurons and centrifugal afferents. Here, we investigated the spatiotemporal dynamic of newborn...

Although feedforward inhibition onto Purkinje cells was first documented 40 years ago, we understand little of how inhibitory interneurons contribute to cerebellar function in behaving animals. Using a mouse line (PC-Deltagamma2) in which GABA(A) receptor-mediated synaptic inhibition is selectively removed from Purkinje cells, we examined how feedf...

In the olfactory bulb, mitral and tufted cells receive GABAergic inhibition at dendrodendritic synapses with granule cells. Recent studies have revealed a remarkable variability in the subunit composition of GABA(a) receptors in dendrodendritic microcircuits, with differential expression patterns of the alpha1 and alpha3 subunits in different subty...

Activity-dependent changes in the strength of synaptic connections in the hippocampus are central for cognitive processes such as learning and memory storage. In this study, we reveal an activity-dependent presynaptic mechanism that is related to the modulation of synaptic plasticity. In acute mouse hippocampal slices, high-frequency stimulation (H...

Characterization of the Different Fractions of the Protocol Used to Isolate Synaptosomes from ASMKO Mice Brains. Western blots using antibodies against the synaptic marker synaptophysin, the myelin marker Myelin basic protein (MBP) and the lysosomal marker LAMP 2, in samples containing equal amount of protein. (6.43 MB EPS)

Effects of Se Treatment on the Lipid Composition of Wt Synaptosomes. Levels of cholesterol (Chol), phospholipids (PE, PC and PS), Ceramide (Cer), SM and Se in wt synaptosomes treated or not with 100 µM Se for 2.5 hours at 370 C, followed by dilution and recentrifugation before lipid analysis (mean±SD; n = 3). (0.76 MB EPS)

Characterizacion of phenotypes in 1-month-old ASMko mice. A. Hippocampal presynaptic plasticity in 1-month-old mice. (a) PPF expressed as mean paired-pulse ratios of fEPSPs recorded at nine interstimulus intervals in wt and ASMko slices. (b) PTP plot in wt and ASMko slices. Arrows indicate tetanus application (100 Hz for one second). For all graphs...

Accumulation of uncatabolized lipid substrates in hippocampal neurons of ASMko mice. A, B, C, D: light-microscopic micrographs of semithin sections through the CA1 region of wt (A,C) and ASMko (B,D) mice depicting the cell bodies of hippocampal pyramidal neurons at 1 month (A,B) and 7 months (C,D) of age. E: Inset of the area depicted with a rectan...

Syntaxin1A Purification. Protein profiles were visualized using Coomassie blue staining of the different fractions of the purification protocol. Molecular weight markers used in the SDS-PAGE are indicated on the left in kDa. (0.51 MB EPS)

Consensus exists that lipids must play key functions in synaptic activity but precise mechanistic information is limited. Acid sphingomyelinase knockout mice (ASMko) are a suitable model to address the role of sphingolipids in synaptic regulation as they recapitulate a mental retardation syndrome, Niemann Pick disease type A (NPA), and their neuron...

DefinitionThis characterizes the lowest level of sound that a listener can reliably detect and is sometimes referred to as threshold of audibility. The units are typically reported in dB sound pressure level (SPL).Psychoacoustics

GABAergic synapses are crucial for brain function, but the mechanisms underlying inhibitory synaptogenesis are unclear. Here, we show that postnatal Purkinje cells (PCs) of GABAAα1 knockout (KO) mice express transiently the α3 subunit, leading to the assembly of functional GABAA receptors and initial normal formation of inhibitory synapses, that ar...

In rodent cerebellar cortex, synaptogenesis occurs entirely postnatally, allowing study of the mechanisms of synapse formation in vivo. Here we monitored the clustering of GABA(A) receptors and the scaffolding protein gephyrin at GABAergic postsynaptic sites during rat cerebellar development. We found that GABA(A) receptors and gephyrin co-aggregat...

Fluctuations in the brain concentrations of neurosteroids are accompanied by changes in the expression of GABA(A) receptor subunits in the cerebral cortex and hippocampus. Here, we investigated the expression of the postsynaptic molecule gephyrin in the cerebral cortex and hippocampus of pregnant rats, as well as in rats treated chronically with co...

We controlled the specificity of pERK immunolabelling by analysing brain sections after SL327 injection. A and B show confocal images of pERK immunofluorescence in the visual cortex of a rat exposed to light for 2.5 minutes after 3 days of dark rearing and injected with SL327 (B), and of another rat that received the same visual stimulation and veh...

To assess the reliability of pERK immunogold localization at synapses, we analyzed consecutive thin sections of the primary visual cortex. Micrographs in A′-A′ illustrate the consistency of labeling in serial sections of an axo-spinous synapse. Immunogold particles decorate a presynaptic terminal (asterisks) in all three sections whereas the juxtap...

Profilins are actin binding proteins essential for regulating cytoskeletal dynamics, however, their function in the mammalian nervous system is unknown. Here, we provide evidence that in mouse brain profilin1 and profilin2 have distinct roles in regulating synaptic actin polymerization with profilin2 preferring a WAVE-complex-mediated pathway. Mice...

Periglomerular (PG) cells in the rodent olfactory bulb are heterogeneous anatomically and neurochemically. Here we investigated whether major classes of PG cells use gamma-aminobutyric acid (GABA) as a neurotransmitter. In addition to three known subtypes of PG cells expressing tyrosine hydroxylase (TH), calbindin D-28k (CB), and calretinin (CR), w...

In the olfactory bulb (OB), odorants induce oscillations in the γ range (20–80 Hz) that play an important role in the processing of sensory information. Synaptic transmission between dendrites is a major contributor to this processing. Glutamate released from mitral cell dendrites excites the dendrites of granule cells, which in turn mediate GABAer...