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Riccardo Bianchi

Riccardo Bianchi
State University of New York Downstate Health Science University · Physiology and Pharmacology

Ph.D.

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58
Publications
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2,108
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Publications

Publications (58)
Article
Full-text available
Alzheimer's disease (AD) is the most frequent neurodegenerative disorder that commonly causes dementia in the elderly. Recent evidence indicate that network abnormalities, including hypersynchrony, altered oscillatory rhythmic activity, interneuron dysfunction, and synaptic depression may be key mediators of cognitive decline in AD. In this review,...
Article
Full-text available
Background and purpose: The 2015 updated US Food and Drug Administration alteplase package insert altered several contraindications. We thus explored clinical factors influencing alteplase treatment decisions for patients with minor stroke. Methods: An expert panel selected 7 factors to build a series of survey vignettes: National Institutes of...
Article
Introduction: The 2015 updated US FDA package insert for rt-PA allows for a greater degree of clinical judgment regarding contraindications; thus there is flexibility in the decision to treat or not to treat. Hypothesis: Identifiable clinical factors influence rt-PA treatment decisions for patients with minor stroke. Methods: An Expert Panel (N=10)...
Article
Full-text available
Down syndrome (DS), caused by trisomy 21, is the most common genetic cause of intellectual disability and is associated with a greatly increased risk of early-onset Alzheimer’s disease (AD). The Ts65Dn mouse model of DS exhibits several key features of the disease including developmental delay and AD-like cognitive impairment. Accumulating evidence...
Article
Full-text available
Cortical and hippocampal network hyperexcitability appears to be an early event in Alzheimer's disease (AD) pathogenesis, and may contribute to memory impairment. It remains unclear if network hyperexcitability precedes memory impairment in mouse models of AD and what are the underlying cellular mechanisms. We thus evaluated seizure susceptibility...
Article
Rapidly improving stroke symptoms (RISSs) are a controversial exclusion for intravenous recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke (AIS). We estimated the frequency of 4 prespecified RISS definitions and explored their relationship to clinical outcome. Pilot, prospective study of AIS patients admitted within 4.5 hour...
Article
Background: Rapidly Improving Stroke Symptoms (RISS) is a controversial exclusion criterion for tPA for acute ischemic stroke (AIS). Prior studies suggest 4-44% of AIS patients eligible are not given tPA solely because of RISS and their outcome is not invariably benign. In 2013 The Re-examining Acute Eligibility for Thrombolysis (TREAT) Task Force...
Article
Minor strokes and rapidly improving stroke symptoms are frequent exclusions for intravenous tissue-type plasminogen activator. We explored factors influencing tissue-type plasminogen activator treatment decision for minor strokes/rapidly improving stroke symptoms. A pilot survey, including 110 case scenarios, was completed by 17 clinicians from 2 a...
Article
Full-text available
Stimulation of group I mGluRs elicits several forms of translation-dependent neuronal plasticity including epileptogenesis. The translation process underlying plasticity induction is controlled by repressors including the fragile X mental retardation protein (FMRP). In the absence of FMRP-mediated repression, a condition that occurs in a mouse mode...
Article
Full-text available
A key determinant of neuronal functionality and plasticity is the targeted delivery of select ribonucleic acids (RNAs) to synaptodendritic sites of protein synthesis. In this paper, we ask how dendritic RNA transport can be regulated in a manner that is informed by the cell's activity status. We describe a molecular mechanism in which inducible int...
Conference Paper
Alzheimer’s disease (AD) patients are at an increased risk of developing seizures and epilepsy. The hypersynchronous network activity leading to elevated risk for seizures in AD may be primarily linked to AD pathology. Thus, many mouse models of AD exhibit epileptiform discharges on electroencephalograms associated with neuropathology. However, it...
Article
Full-text available
A set of spontaneous hunger sensations, Initial Hunger (IH), has been associated with low blood glucose concentration (BG). These sensations may arise pre-meal or can be elicited by delaying a meal. With self-measurement of BG, subjects can be trained to formally identify and remember these sensations (Hunger Recognition). Subjects can then be trai...
Article
Plastic changes in cortical activities induced by group I metabotropic glutamate receptor (mGluR) stimulation include epileptogenesis, expressed in vitro as the conversion of normal neuronal activity to persistent, prolonged synchronized (ictal) discharges. At present, the mechanism that maintains group I mGluR-induced plasticity is not known. We e...
Article
Many neuropsychiatric symptoms of fragile X syndrome (FXS) are believed to be a consequence of altered regulation of protein synthesis at synapses. We discovered that lovastatin, a drug that is widely prescribed for the treatment of high cholesterol, can correct excess hippocampal protein synthesis in the mouse model of FXS and can prevent one of t...
Chapter
Full-text available
Stimulation of group I mGluRs elicits ictal-like responses from normal quiescent hippocampal slices. Ictal-like responses once induced become persistent and show no fading even upon washout of the agonist. The conversion of normal neuronal activity to long-lasting epileptiform discharges resembles epileptogenesis and effects of group I mGluRs on hi...
Article
Full-text available
Group I metabotropic glutamate receptors (mGluRs) stimulation activates translation-dependent epileptogenesis in the hippocampus. This translation is regulated by repressors, including BC1 RNA and fragile X mental retardation protein (FMRP). Recent data indicate that group I mGluR stimulation exerts bidirectional control over FMRP level by activati...
Article
Group I metabotopic glutamate receptors (mGluRs) can initiate protein synthesis-dependent intracellular signaling processes that can result in enhanced expression of ictal-length discharges. Studies reveal that the fragile X syndrome phenotype is mediated by excessive mGluR-driven protein synthesis. Defective endogenous regulation of mGluR effects...
Data
Initial epileptogenic responses were triggered significantly faster in BC1−/− Fmr1−/− dKO animals. Percentages of animals in uncontrolled running after 10 s, 15 s, and 20 s were significantly higher in the BC1−/− Fmr1−/− group than in either the BC1−/− or the Fmr1−/− group (Generalized Linear Model, followed by post-hoc tests of pairs of groups usi...
Article
Full-text available
BC RNAs and the fragile X mental retardation protein (FMRP) are translational repressors that have been implicated in the control of local protein synthesis at the synapse. Work with BC1 and Fmr1 animal models has revealed that phenotypical consequences resulting from the absence of either BC1 RNA or FMRP are remarkably similar. To establish functi...
Article
Regulatory RNAs are being increasingly investigated in neurons, and important roles in brain function have been revealed. Regulatory RNAs are non-protein-coding RNAs (npcRNAs) that comprise a heterogeneous group of molecules, varying in size and mechanism of action. Regulatory RNAs often exert post-transcriptional control of gene expression, result...
Article
Full-text available
Background. Excessive energy intake has been implicated in diabetes, hypertension, coronary artery disease, and obesity. Dietary restraint has been unsuccessful as a method for the self-regulation of eating. Recognition of initial hunger (IH) is easily learned, can be validated by associated blood glucose (BG) concentration, and may improve insulin...
Article
Full-text available
Regulatory RNAs have been suggested to contribute to the control of gene expression in eukaryotes. Brain cytoplasmic (BC) RNAs are regulatory RNAs that control translation initiation. We now report that neuronal BC1 RNA plays an instrumental role in the protein-synthesis-dependent implementation of neuronal excitation-repression equilibria. BC1 rep...
Article
Chromosomal abnormalities include aberrations of chromosome number and/or structure, such as trisomy, translocation, duplication, deletion. These abnormalities are caused by errors in chromosome disjunction during meiosis and result in conditions that range from prenatal death to relatively mild syndromes in adulthood. Common traits of syndromes du...
Article
Full-text available
Stimulation of group I metabotropic glutamate receptors (mGluRs) by the agonist (S)-dihydroxyphenylglycine in the hippocampus transforms normal neuronal activity into prolonged epileptiform discharges. The conversion is long lasting in that epileptiform discharges persist after washout of the inducing agonist and serves as a model of epileptogenesi...
Article
Full-text available
Activation of group I metabotropic glutamate receptors (mGluRs) leads to a concerted modulation of spike afterpotentials in guinea pig hippocampal neurons including a suppression of both medium and slow afterhyperpolarizations (AHPs). Suppression of AHPs may be long-lasting, in that it persists after washout of the agonist. Here, we show that persi...
Article
The group I metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG) elicited two phases of synchronized neuronal (epileptiform) discharges in hippocampal slices: an initial phase of short duration discharges followed by a phase of prolonged discharges. We assessed the involvement of transient receptor potential canonical (TRPC...
Article
Full-text available
The will to eat is a decision associated with conditioned responses and with unconditioned body sensations that reflect changes in metabolic biomarkers. Here, we investigate whether this decision can be delayed until blood glucose is allowed to fall to low levels, when presumably feeding behavior is mostly unconditioned. Following such an eating pa...
Article
Full-text available
The pharmacology of a slowly inactivating outward current was examined using whole cell patch-clamp recordings in CA3 pyramidal cells of guinea pig hippocampal slices. The current had a low activation threshold (about -60 mV) and inactivated slowly (time constant of 3.4 +/- 0.5 s at -50 mV) and completely at membrane voltages depolarized to -50 mV....
Article
Full-text available
Rhythmic oscillatory activities at the theta frequency (4-12Hz) in the hippocampus have long-attracted attention because they have been implicated in diverse brain functions, including spatial cognition. Although studies based on pharmacology and lesion experiments suggested heterogeneity of these rhythms and their behavioral correlates, controvers...
Article
Mutations in FMR1, which encodes the fragile X mental retardation protein (FMRP), are the cause of fragile X syndrome (FXS), an X-linked mental retardation disorder. Inactivation of the mouse gene Fmr1 confers a number of FXS-like phenotypes including an enhanced susceptibility to epileptogenesis during development. We find that in a FXS mouse mode...
Article
The group I metabotropic glutamate receptor subtypes, mGluR1 and mGluR5, have both distinct and overlapping actions in epileptogenesis. Data are reviewed revealing how activation of these receptor subtypes participates in the induction and maintenance of the long-lasting epileptiform discharges elicited in the hippocampal circuit. Differences in th...
Article
Local protein synthesis in dendrites is thought to provide a mechanism for long-lasting modifications of synapses in response to physiological activity and behavioral experience. New synthesis of dendritic proteins may be triggered by various paradigms, including induction of epileptiform activity. Prerequisite for such modulated synthesis is a mec...
Article
Transient application of group I metabotropic glutamate receptor (mGluR) agonists to hippocampal slices produces ictal-like discharges that persist for hours after the removal of the agonist. This effect of group I mGluR stimulation--converting a 'normal' hippocampal slice into an 'epileptic-like' one--may represent a form of epileptogenesis. Becau...
Article
Full-text available
Transient stimulation of group I metabotropic glutamate receptors (mGluRs) induces persistent prolonged epileptiform discharges in hippocampal slices via a protein synthesis-dependent process. At present, the signaling process underlying the induction of these epileptiform discharges remains unknown. We examined the possible role of extracellular s...
Article
Full-text available
Despite clear indications of their importance in lower organisms, the contributions of protein tyrosine phosphatases (PTPs) to development or function of the mammalian nervous system have been poorly explored. In vitro studies have indicated that receptor protein tyrosine phosphatase alpha (RPTPalpha) regulates SRC family kinases, potassium channel...
Article
Full-text available
Application of group I metabotropic glutamate receptor (mGluR) agonists elicits seizure discharges in vivo and prolonged ictal-like activity in in vitro brain slices. In this study we examined 1) if group I mGluRs are activated by synaptically released glutamate during epileptiform discharges induced by convulsants in hippocampal slices and, if so,...
Article
Application of group I metabotropic glutamate receptor (mGluR) agonists elicits seizure discharges in vivo and prolonged ictal-like activity in in vitro brain slices. In this study we examined 1) if group I mGluRs are activated by synaptically released glutamate during epileptiform discharges induced by convulsants in hippocampal slices and, if so,...
Article
The group I metabotropic glutamate receptor agonist DHPG has been shown to produce two major effects on CA3 pyramidal cells at rest: a reduction in the background conductance and an activation of a voltage-gated inward current (I(mGluR(V))). Both effects contribute to depolarising CA3 pyramidal cells and the latter has been implicated in eliciting...
Article
Activation of metabotropic glutamate receptors (mGluRs) often produces long-lasting effects on the excitability of cortical neurons. For example, mGluR stimulation induces long-term potentiation or depression of excitatory synaptic transmission in the hippocampus. Similarly, the effects of mGluRs on cortical epileptiform activities also are endurin...
Article
Full-text available
Activation of metabotropic glutamate receptors (mGluRs) produces multiple effects in cortical neurons, resulting in the emergence of network activities including epileptiform discharges. The cellular mechanisms underlying such network responses are largely unknown. We examined the properties of group I mGluR-mediated cellular responses in CA3 neuro...
Article
Fluorescent Ca2+ indicator dyes can be introduced into cells through the same microelectrode used for intracellular voltage recording. Simultaneous measurement of cell membrane potential and intracellular Ca2+ concentration can be very helpful in interpreting the mechanisms of Ca2+ increases. This chapter describes fluorescence image acquisition us...
Article
Cultures of primary neurons or thin brain slices are typically prepared from immature animals. We introduce a method to prepare hippocampal slice cultures from mature rats aged 20–30 days. Mature slice cultures retain hippocampal cytoarchitecture and synaptic connections up to 3 months in vitro. Spontaneous epileptiform activity is rarely observed...
Article
A unique property of the group I metabotropic glutamate receptor (mGluR)-induced depolarization in hippocampal cells is that the amplitude of the depolarization is larger when the response is elicited at more depolarized membrane potentials. Our understanding of the conductance mechanism underlying this voltage-dependent response is incomplete. Thr...
Article
Application of the metabotropic glutamate receptor (mGluR) agonist (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) or the selective group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) depolarized both CA3 and CA1 pyramidal cells in guinea pig hippocampal slices. Simultaneous recordings of voltage and intracellular Ca2+ levels reve...
Article
Full-text available
Considerable information is available regarding the role of ionotropic glutamate receptors in the generation of interictal spikes. Progress in the study of metabotropic glutamate receptors (mGluRs) makes clear that activation of these receptors can contribute greatly to seizure discharges and epileptogenesis. The effects of activation of the differ...
Article
1. Intracellular and extracellular recordings of CA1 and CA3 neurones were performed in guinea-pig hippocampal slices to examine synaptic activities dependent on metabotropic glutamate receptors (mGluRs). 2. Long burst activities were elicited by 4-aminopyridine in the presence of ionotropic glutamate receptor and GABAA receptor blockers (6-cyano-7...
Article
Electrophysiological recordings from neurons of rat frontal neocortical slices have been used to investigate the action of the beta-carboline methyl-6,7-dimethoxy-4-ethyl-beta- carboline-3-carboxylate (DMCM), on responses to gamma-aminobutyric acid (GABA) and on the excitability of the neurons. Iontophoretic application of GABA close to the intrace...
Article
1. Carbachol effects on CA3 hippocampal cells were studied in the absence of ionotropic glutamatergic and GABAergic transmission with intracellular and extracellular recordings from guinea pig septohippocampal slices. 2. In all experiments the perfusing solution contained ionotropic glutamate and gamma-aminobutyric acid (GABA) receptor blockers [6-...
Article
In surviving slices of rat hippocampus, isolated from 1 to 4 weeks after septal lesioning by ibotenic acid, extracellular and intracellular responses were recorded in region CA3. Spontaneous and evoked epileptiform focal discharges are described, synchronous with paroxysmal depolarization shifts (PDS) of the membrane potential and with burst activi...
Article
Hippocampal slices from guinea-pigs were used to examine the long-term potentiation (LTP) of the N-methyl-d-aspartate (NMDA)-mediated excitatory postsynaptic potential (EPSP). Intracellular recordings were performed from CA1 pyramidal neurons in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5 - 10 microM) and picrotoxin (50 microM). I...
Article
In hippocampal pyramidal cells (HPCs), Dopamine (DA) application (1 microM) produced, in 50% of recorded cells, an hyperpolarization of the resting membrane potential (r.m.p.) and an increase of the afterhyperpolarization (AHP) amplitude and duration in 79% of recorded cells. DA-induced effects on both the r.m.p. and AHP were mimicked by bath appli...

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Project
The two diabetic patients object of present report, were observed within the recruitment program that we described in the section “Studies in Adults”. We treated them with the usual IH training. After meal suspension up to 48 hours, all children and all adults manifested IH arousal. Sometimes, adults denied any perception of IH in their past life. Also in these adults, IH arouse as a spontaneous event after hours or a day of no meal consumption and our interpretation was that these adults ate by conditioned reflexes. Their past arousals of hunger were conditioned and two days of meal suspension was sufficient to evoke the arousal of Initial Hunger (IH). On the contrary, the two diabetic patients denied any hunger arousal and maintained either high BG and, under metformin, normal preprandial BG before the meal, respectively (99 mg/dL, 95 mg/dL after correction; 77 and 81 mg/L in the other diabetic patient). This means that their initial body weight was associated with energy stores so large that covered 60% to 70% of daily metabolic expenditure by fatty acids delivery into blood for months, 30% – 60% being covered by daily intake. The width of the exit gate from fatty stores is correlated to the amount of stored fat []. More precisely with the percentage of replenishment of fatty cells []. Both patients maintained happy physical and mental activity and improved their blood examinations, suggesting that they maintained an optimal energy availability and this is confirmed by BG. Both patients maintained also sufficient availability of protein, mineral and vitamins. A copious and variated consumption of vegetables and a limited consumption of animal food (100 to 200 grams per day) may offer more essential principles for life than a diet rich in carbohydrates o fats. Not starchy vegetables between half and one kg [] and 100 - 200 grams of chicken or fish might cope with this food project. Energy intake from carbohydrates or fat is not necessary. This study suggests that the NIDD patient requires an adequate loss of fatty stores and of the associated decrease of fatty acids influx into blood to recover hunger sensations. Body weight loss is rather easy because hunger does not arise. This is a suggestive hypothesis that becomes demonstrated after repetition of this achievement for 19 times out of 20 investigated patients. This implies no harms or risks. In doubts, energy availability may be checked three times a day at the lowest points during the day by BG measurements. A preliminary study may be initiated on 10 - 20 diabetic patients (NIDD). The primary objective may be the achievement of the normal BG condition, i.e., a preprandial decrease to 76.6 ± 3.7 mg/dL. The body weight loss may be between 10% – 20%. After this achievement the NIDD patients do not differ from the many healthy subjects we followed. An IH meal pattern allows them normal, healthy and long life without any overall inflammation. That means remaining exposed to the development of fattening/insulin resistance in absence of an ordinate skill to unremittingly contrast meal by meal positive energy balance.