1,720,987 research outputs found
'Metabotropic' glutamate receptors in rat hypothalamus: characterization and developmental profile.
No full textExcitatory amino acids (EAAs) are known to stimulate neurohormone release through the activation of ion-channel-linked receptors (ionotropic receptors). Here we report that a receptor for EAAs linked to polyphosphoinositide hydrolysis (metabotropic receptor) is also present at the hypothalamus where its expression is developmentally regulated. Stimulation of [3H]inositolmonophosphate ([3H]InsP) formation by quisqualate (EC50 = 1.5 microM), ibotenate (EC50 = 100 microM) and trans-1-amino-1,3-cyclopentanedicarboxylic acid (t-ACPD; EC50 = 30 microM) is extremely high (up to 50-fold) in the first 10 days of postnatal life, progressively declines during maturation and is virtually absent in the adult. Stimulation of phosphoinositide hydrolysis by quisqualate, ibotenate and t-ACPD is more pronounced than that induced by classical neurotransmitters that stimulate inositol phosphate formation such as norepinephrine and carbamylcholine. Agonists of the ionotropic glutamate receptor such as kainate, NMDA and alpha-amino-3-hydroxy-5-methyl-5-isoxazolpropionate (AMPA), do not modify inositol phosphate accumulation in hypothalamic slices. The selective antagonist of quisqualate metabotropic receptor, D,L-2-amino-3-phosphonopropionate (AP3), produces a slight stimulation of phosphoinositide hydrolysis, but potently antagonizes the stimulation produced by quisqualate and t-ACPD
Inositol hexakisphosphate stimulates 45Ca2+ uptake in anterior pituitary cells in culture.
No full textInositol hexakisphosphate (InsP6) is thought to act as an intracellular signal molecule in the central nervous system. We report that InsP6 stimulates 45Ca2+ uptake in cultured anterior pituitary cells. This effect is concentration-dependent, is mimicked by inositol-pentakis phosphate (InsP5) but not by inositol-tetrakis phosphate (InsP4), is present after 2 min of incubation, is independent of extracellular Na+ and insensitive to nifedipine and verapamil. These results suggest that InsP6, a putative metabolite of the inositol cycle, may regulate transmembrane mechanism in the pituitary
Alzheimer's disease research enters a "new cycle": How significant?
No full textRecent evidence suggests a link between the aberrant re-expression of cell cycle proteins in adult neurons of the Alzheimer's disease brain and the process of apoptotic degeneration, Here we will discuss this unexpected phenomenon as related to the mechanisms of beta-amyloid toxicity, and its significance for therapeutic possibilities
Neurobiological determinants of depressive-like symptoms in rodents
Full text linkLa depressione è una delle malattie psichiatriche più frequenti, la cui prevalenza ha raggiunto
proporzioni epidemiche negli ultimi decenni. A questo proposito, diversi studi riportano una
maggior incidenza di depressione nelle donne rispetto agli uomini, sebbene le ragioni di questa
differenza di genere non siano state ancora pienamente comprese. I principali sintomi della
depressione includono umore depresso, anedonia (ridotta capacità di provare appagamento o
interesse per attività comunemente ritenute piacevoli), irritabilità, difficoltà di concentrazione,
ritiro sociale e anomalie dell'appetito e del sonno, i cosiddetti "sintomi neurovegetativi”.
Numerosi disordini mentali come la schizofrenia, i disturbi bipolari, il Morbo di Alzheimer, i
disturbi d'ansia, i disturbi dello spettro autistico (ASD) e le malattie correlate allo stress, possono
manifestarsi come comorbidità della malattia depressiva. Inoltre, la depressione si presenta
spesso durante la fase prodromica del Morbo di Alzheimer, della schizofrenia e dei disturbi
bipolari.
Diete, fattori genetici e stile di vita contribuiscono all'insorgenza e alla progressione delle malattie
mentali. Per quanto riguarda i fattori dietetici, gli acidi grassi polinsaturi (PUFAs) hanno ricevuto
grande attenzione negli ultimi decenni, soprattutto a causa dell’aumentato consumo di junk food,
tipico dei Paesi Occidentali, che ha portato ad una drammatica riduzione nell’assunzione di n-3
PUFA e ad uno smodato aumento del consumo di n-6 PUFA. A questo proposito, nei capitoli 2 e 3
di questa tesi, sono presentati i nostri dati riguardanti gli effetti di una dieta ricca di n-3 PUFA e di
una dieta povera di n-3 PUFA su ratte femmine sottoposte, dal concepimento fino all’età adulta,
alle sopracitate supplementazioni dietetiche. I nostri risultati hanno mostrato che l'esposizione
cronica alla dieta povera di n-3 PUFA può portare ad alterazioni di parametri comportamentali e
neurochimici, correlate a sintomi depressivo-ansiosi. In particolare, nelle ratte sottoposte alla
dieta povera di n-3 PUFA, è stato riscontrato un aumento della frequenza dell'immobilità e una
diminuzione della frequenza di attività nel test del nuoto forzato (FST). In un altro set di animali
sottoposti allo stesso trattamento, l’Open Field test ha mostrato un aumento del tempo trascorso
facendo self-grooming e di quello speso nella periferia dell'arena. Pertanto, i nostri risultati
comportamentali suggeriscono che la protratta carenza di n-3 PUFA è in grado di indurre sintomi
simil-depressivi e simil-ansiogeni nelle ratte femmine. Abbiamo successivamente studiato le
possibili alterazioni neurochimiche alla base di queste alterazioni comportamentali, identificando
una significativa diminuzione della serotonina (5-HT) corticale e del fattore di crescita neuronale
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(NGF) nelle ratte esposte alla dieta povera di n-3 PUFA, accompagnati da un aumento del turnover
della serotonina. Inoltre, nel capitolo 3, abbiamo mostrato che la dieta povera in n-3 PUFA
determina un’iperattivazione dell'asse ipotalamo-ipofisi-surrene (HPA), mediante l'aumento della
noradrenalina e del fattore di rilascio della corticotropina (CRF) in ipotalamo e l’incremento del
corticosterone plasmatico (accompagnati da un aumento di noradrenalina e serotonina in
amigdala), così come da un incremento del glutammato e una diminuzione dell’ acido gammaaminobutirrico
(GABA) sia nella corteccia prefrontale che nell'amigdala. In ultima analisi, le ratte
femmine esposte ad una dieta povera di n-3 PUFA hanno mostrato un aumento plasmatico del
peptide beta amiloide solubile (Aβ)1-42.
Il peptide solubile Aβ1-42 sta recentemente assumendo grande importanza nella patogenesi della
depressione, in quanto la depressione si presenta frequentemente come comorbidità sia della
malattia di Alzheimer sia di altre malattie neurodegenerative. A questo proposito, il nostro gruppo
ha precedentemente dimostrato che la somminiztrazione intracerebroventricolare (icv) di Aβ è in
grado di evocare un fenotipo simil-depressivo in ratti adulti maschi. Nel capitolo 2 di questo lavoro
di tesi, abbiamo riprodotto per la prima volta il modello simil-depressivo indotto dalla
somministrazione di Aβ nelle ratte femmine, valutando parametri comportamentali e
neurochimici. I nostri risultati hanno confermato il profilo depressivo indotto da Aβ anche nelle
ratte femmine. Inoltre, il profilo simil-depressivo Aβ-indotto è stato revertito nelle ratte esposte
ad una dieta ricca di n-3 PUFA, indicando un possibile effetto benefico della supplementazione di
n-3 PUFA nel trattamento dei disturbi depressivi. In conclusione, i nostri dati suggeriscono che le
alterazioni della trasmissione monoaminergica, accompagnate da modifiche del NGF e disfunzioni
dell'asse HPA, possono essere considerate importanti determinanti neurobiologici che
contribuiscono alla patogenesi dei sintomi simil-depressivi indotti dalla carenza di n-3 PUFA e dalla
somministrazione del peptide Aβ solubile.
Negli ultimi decenni le diagnosi dei disturbi psichiatrici sono state basate essenzialmente su
sintomi soggettivi e su segni osservabili. Sebbene i sintomi costituiscano un importante punto di
partenza, i fattori genetici e neurobiologici sottesi a questi sintomi devono essere approfonditi.
Pertanto, l’impiego di modelli animali può risultare molto utile al fine di studiare
longitudinalmente le alterazioni comportamentali traslabili ai sintomi nell’uomo e, in ultima
analisi, indagare sulla neurobiologia sottesa per identificarne l'eziopatogenesi.
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Pertanto, in questo lavoro di tesi, sono stati investigati i meccanismi neurobiologici alla base di
sintomi simil-depressivi comuni a molte malattie neuropsichiatriche e neurodegenerative,
utilizzando diversi paradigmi e modelli animali.
Per poter analizzare in maniera approfondita e traslazionale i principali sintomi simil-depressivi,
occorre tener conto anche della sfera sociale. Un importante sintomo simil-depressivo che
colpisce la sfera sociale è il ritiro sociale. Il ritiro sociale, definito come la mancanza di desiderio di
avere contatti sociali, è un sintomo precoce di un'ampia varietà di malattie neuropsichiatriche, tra
cui la schizofrenia, l'ASD e la depressione maggiore.
A questo proposito, nel capitolo 4 e 5, abbiamo investigato le alterazioni comportamentali relative
alla socialità e al ritiro sociale, utilizzando un nuovo paradigma comportamentale chiamato
“Visible Burrow System” (VBS). Il VBS è un ambiente semi-naturale, costituito da un tunnel e
numerose tane costantemente al buio e un'arena con un normale ciclo luce/buio (12h/12h), utile
per analizzare le dinamiche sociali che si verificano naturalmente nelle colonie di roditori. In
particolare, abbiamo individuato alterazioni comportamentali correlabili al ritiro sociale in colonie
di topi C57BL/6J, utilizzati come ceppo di controllo, e due linee transgeniche, i topi BTBR e i topi
Pcdh9-Knockout (KO). I topi BTBR sono ampiamente utilizzati per le loro somiglianze con i deficit
tipici dell’ASD, poiché presentano comportamenti stereotipati, disfunzioni nella vocalizzazione e
ridotte interazioni sociali, mentre i Pcdh9-KO sono stati recentemente studiati come modelli similschizofrenici,
simil-depressivi e simil-autistici.
I nostri risultati hanno mostrato che i topi BTBR presentano deficit nei comportamenti sociali e
hanno una preferenza per i comportamenti non sociali rispetto ai topi C57BL/6J nel VBS, con
caratteristiche tipiche del ritiro sociale. Al contrario, non abbiamo trovato differenze di
socializzazione nelle colonie composte da Pcdh9 omozigoti e eterozigoti KO e Wild Type (WT),
indicando l’assenza di deficit della sfera sociale nei topi Pcdh9 KO stabulati insieme ad i WT nel
VBS. A questo proposito, studi futuri saranno focalizzati su una maggiore caratterizzazione del
fenotipo sociale dei Pcdh9 KO, in assenza di stimoli sociali. Infatti, le colonie, formate da topi di
genotipo misto e di sesso misto, sono considerate setting altamente sociali, utili a migliorare i
deficit sociali eventualmente riscontrati. In conclusione, il nostro studio ha validato l'utilità del VBS
come paradigma comportamentale per studiare le disfunzioni sociali e potrebbe essere
ulteriormente impiegato per testare trattamenti farmacologici mirati al loro ripristino.
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A questo punto, un’analisi della possibili alterazioni neurobiologiche responsabili del ritiro sociale
si è resa necessaria. A tal fine, nel capitolo 4 di questo lavoro di tesi, abbiamo analizzato il
contenuto di GABA e glutammato nella corteccia prefrontale e nell’ amigdala di colonie di topi
C57BL/6J e BTBR, identificando una significativa diminuzione del GABA e un significativo aumento
del glutammato in entrambe le aree nei topi BTBR. Abbiamo così ipotizzato che la diminuzione di
GABA e il corrispondente aumento del glutammato nella corteccia prefrontale e nell'amigdala
potrebbero essere responsabili della ridotta socializzazione e dell'aumento del ritiro sociale nei
topi BTBR. Pertanto, la stimolazione della neurotrasmissione GABAergica e l’attenuazione del tono
glutammatergico potrebbero rappresentare possibili targets terapeutici per il trattamento del
ritiro sociale, tipico di numerose malattie neuropsichiatriche e neurodegenerative.
Inoltre, nel capitolo 5 di questa tesi, abbiamo misurato i livelli di GABA e glutammato nella
corteccia somato-sensoriale di colonie di topi Pcdh9 e abbiamo evidenziato l’assenza di differenze
nel contenuto di GABA tra i tre genotipi, sia nei topi raggruppati in colonie nel VBS, che nei topi
stabulati nelle gabbie standard. Contrariamente, i topi Pcdh9-KO omozigoti, stabulati nelle gabbie
standard, hanno riportato un aumento di glutammato rispetto ai topi KO eterozigoti ed ai WT,
mentre nessuna differenza di genotipo è stata riscontrata nei livelli di glutammato delle le colonie
del VBS. Di conseguenza, l'aumento del glutammato riportato dai Pcdh9 KO omozigoti stabulati in
gabbie standard e non riscontrato nei KO omozigoti raggruppati nelle colonie del VBS, suggerisce
un effetto positivo di questo ambiente altamente sociale, in grado di revertire l'aumento di
glutammato indotto dalla deficienza del gene Pcdh9.
In conclusione, il presente lavoro di tesi è stato focalizzato sullo studio di differenti pathways
neurobiologici in grado di provocare sintomi simil-depressivi caratteristici di molti disturbi
neuropsichiatrici, al fine di sviluppare un approccio multifattoriale.
Al fine di migliorare le attuali opzioni terapeutiche e sviluppare nuovi trattamenti sicuri ed efficaci,
occorre necessariamente considerare l'influenza dei fattori sociali, ambientali e alimentari, così
come il ruolo delle comorbidità nell’eziopatogenesi dei sintomi simil-depressivi, in maniera da
individuare i corretti substrati neurobiologici responsabili della comparsa di tali sintomi.Depression is one of the most common psychiatric diseases; indeed the prevalence of depressive
symptoms has reached epidemic proportions during the last few decades. Several studies reported
that depression is more prevalent in women compared to men. Although the reasons for this
gender pre-dominance in depression is not understood, women show different hormonal
responses that might ultimately influence behaviours and brain functions.
The core symptoms of depression include depressed mood, anhedonia (reduced ability to
experience pleasure from natural rewards), irritability, difficulties in concentrating, social
withdrawal (withdrawal from social contact that derives from indifference or lack of desire to have
social contact) and abnormalities in appetite and sleep, the so called “neurovegetative
symptoms”.
Depression has shown to be comorbid with several neuropsychiatric diseases, such as
schizophrenia, bipolar disorders, Alzheimer’s diseases, anxiety disorders, autism spectrum
disorders (ASD) and stress-related diseases. Moreover, depression often occurs during the
prodromic phase of Alzheimer’s disease, schizophrenia and bipolar disorders.
Diets, genetics and lifestyle contribute to the onset and progression of mental illnesses. Regarding
dietary factors, Polyunsaturated Fatty Acids (PUFA) have received great attention during the last
decades, particularly due to the trend towards a poor n-3 PUFA intake of modern Western diets. In
this regard, in chapter 2 and 3 of the present thesis, effects of n-3 PUFA deficient and n-3 PUFA
enriched diets on female rat offspring have been investigated. Our results reported that chronic
exposure to n-3 PUFA deficient diet leads to highly detrimental consequences in behavioural and
neurochemical parameters related to depressive- and anxiety-like symptoms. In particular, we
found an increase in immobility and a decrease in swimming frequency in Forced Swimming test in
n-3 PUFA deficient females, and, in the Open Field test, we showed an increase in time spent
performing self-grooming and time spent in the periphery of the arena. Hence, our behavioural
results showed that lifelong n-3 PUFA deficiency is able to elicit depressive- and anxiety-like
symptoms in female rats. Therefore, we investigated neurochemical changes underlying these
behavioural alterations. We found a significant decrease in cortical serotonin and Nerve Growth
Factor in n-3 PUFA deficient females, accompanied by an increase in serotonin turnover.
Moreover, in chapter 3, we showed that n-3 PUFA deficient diet led to hyperactivation of the HPA
axis, in particular increase in hypothalamic noradrenaline and corticotrophin-releasing factor and
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also increase in plasmatic corticosterone, accompanied by an increase in amygdaloidal
noradrenaline and serotonin and an increase in glutamate and a decrease of GABA in both
prefrontal cortex and amygdala. Ultimately, we found an increase in plasmatic soluble beta
amyloid (Aβ) 1-42 peptide in females exposed to n-3 PUFA deficient diet.
Interestingly, soluble Aβ1-42 peptide is receiving great importance in the development of
depression, also since depression is highly comorbid with Alzheimer’s disease and other
neurodegenerative illnesses. Accordingly, we have previously shown that central Aβ injection is
able to elicit depressive-like phenotype in male rats. Thus, in chapter 2, we reproduced for the first
time the Aβ-induced depressive-like model in female rats, evaluating behavioural and
neurochemical outcomes. Our results confirmed the Aβ-induced depressive-like profile also in
female rats. Moreover, the Aβ-induced depressive-like profile was reversed by n-3 PUFA
supplementation, indicating a possible therapeutic role of n-3 PUFA in the treatment of the
burden of depressive disorders. Taken together, our data suggest that monoamine impairments,
accompanied by Nerve Growth Factor alterations and HPA axis dysfunctions, might be considered
important neurobiological determinants contributing to the pathogenesis of depressive-like
symptoms induced by n-3 PUFA deficiency and soluble Aβ administration.
During the last decades, diagnosis in psychiatry only focused on subjective symptoms and
observable signs. Although symptoms are an important starting point, genetics and neurobiology
underlying these symptoms need to be deeply investigated. To achieve this purpose, animal
models can be really helpful to longitudinally study behavioural alterations resembling human
symptoms, and ultimately investigate the underlying neurobiology in order to unravel the
etiopathogenesis. Therefore, in this thesis, we focused on depressive-like symptoms that occur in
several neuropsychiatric and neurodegenerative diseases, and, using different animal paradigms
and models, we tried to disentangle the neurobiological determinants behind these symptoms.
Intriguingly, in order to deeply investigate depression core symptoms in a translational way, the
social sphere need to be taken into account. An important depressive-like symptom affecting the
social sphere is social withdrawal. Social withdrawal, defined as lack of desire to have social
contact, is an early symptom of a wide variety of neuropsychiatric diseases, including
schizophrenia, Autism Spectrum Disorders (ASD) and major depression.
In chapter 4 and 5, we investigated behavioural alterations related to sociability and social
withdrawal, using a behavioural paradigm called the Visible Burrow System (VBS). The VBS is a
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semi-natural environment, with burrows and an open area, useful to study social dynamics that
naturally occur in mixed-sex rodent colonies, firstly developed by Blanchard group. In particular
we identified and validated behavioural readouts to assess sociability and social withdrawal
features in C57BL/6J mice colonies, used as control strain, and two mutant lines, BTBR inbred
strain and a Pcdh9-deficient line. The BTBR strain is a widely used strain for its similarities with
human ASD deficits, such as repetitive behaviour, impaired communication and reduced social
interactions, while Pcdh9 gene Knockout (KO) mice are known to affect social behaviour in mice
and may, through the core deficit in sensory processing be relevant to a wide variety of
neuropsychiatric disorders, such as schizophrenia, major depression and ASD.
Our results showed that BTBR mice performed less social behaviours and have a preference for
non-social behaviours compared to C57BL/6J mice in the VBS. Thus, our results reported a trend
towards social withdrawal in BTBR mice, opening to a deep investigation of the underlying
neurobiology that gives rise to this important symptom. Hence, our study validated the suitability
of VBS as a behavioural paradigm to assess sociability and social withdrawal features. Conversely,
we found no differences in terms of social behaviours and non-social behaviours among VBS
colonies composed of Pcdh9 Homozygous (HOM) and Heterozygous (HET) KO and Wild Type (WT)
mice, indicating no disrupted sociability of Pcdh9-deficient mice when housed together with WT in
the VBS. In this regard, future studies are required to better understand the HOM Pcdh9 KO social
phenotype without the presence of social stimuli. Indeed, VBS colonies formed by mixed-genotype
and mixed-sex mice are considered highly social environment, and these strong social stimuli
might be helpful to improve putative social deficits. In conclusion, the VBS can be used as a tool to
study behavioural dysfunctions and might be further used as a behavioural paradigm to test
pharmacological treatments aiming at restoring social dysfunctions that commonly occur in
several neuropsychiatric disorders, such as social withdrawal.
Furthermore, in order to investigate neurobiology behind sociability and social withdrawal, in
chapter 4, we analyzed GABA and glutamate content in prefrontal cortex and amygdala of
C57BL/6J and BTBR colonies and we found a significant decrease of GABA and a significant
increase of glutamate in both areas of BTBR mice.
Intriguingly, the decrease in GABA and the corresponding increase in glutamate in prefrontal
cortex and amygdala might be responsible for the observed decrease in social behaviour and
increase in social withdrawal characteristics in BTBR strain. Thus, enhancement of GABA
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neurotransmission and consequent attenuation of glutamatergic tone might be a possible
therapeutic strategy to treat social withdrawal symptoms that primarily occur in many
neuropsychiatric and neurodegenerative diseases.
Moreover, in chapter 5, we measured GABA and glutamate levels in somatosensory cortex of
Pcdh9 colonies and we found that there were no differences in GABA content among the three
genotypes in both VBS colonies and standard housing condition. Otherwise, glutamate was
significantly increased only in HOM Pcdh9-deficient mice housed in standard cage, while no
genotype differences were found in glutamate levels among VBS colonies. Hence, the glutamate
increase found in HOM Pcdh9 KO mice housed in standard cages and not found in HOM Pcdh9 KO
mice housed in VBS colonies points towards a putative beneficial effect of this highly social
environment on glutamate increase induced by Pcdh9 deletion.
In conclusion, in the present thesis, we investigated the heterogeneity underlying the
neurobiology of depressive like-symptoms, that might be shared across different neuropsychiatric
disorders. In this way a multifactorial perspective will be developed. Hence, in order to improve
the current pharmacological approach and further develop new safe and effective treatments, the
influence of social, environmental and dietary factors, together with comorbidities, need to be
considered to ultimately target the correct neurobiological substrates that give rise to different
depressive-like symptoms shared across various brain diseases
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Adenosine deaminase increases release of excitatory amino acids through a mechanism independent of adenosine depletion.
No full textAddition of adenosine deaminase to cultured cerebellar neurones, led to large increases in the influx of 45Ca2+ and hydrolysis of polyphosphoinositide. These effects were inhibited or attenuated by glutamate receptor antagonists (AP5 or MK-801) and were not observed in cells stimulated by maximum concentrations of glutamate or quisqualate. Stimulation of the influx of 45Ca2+ and hydrolysis of phosphoinositide by adenosine deaminase may be secondary to an enhanced release of endogenous glutamate that in turn activates specific excitatory amino acid receptors. Accordingly, adenosine deaminase potently increased release of D-[3H]aspartate, an effect that requires the presence of extracellular Na+ and is insensitive to inhibition by MK-801. None of the effects of adenosine deaminase may be simply related to a fall in endogenous adenosine. In fact, the action of adenosine deaminase was neither reversed by agonists (L-PIA or NECA), nor mimicked by antagonists (IBMX or theophylline) of adenosine receptors. It is speculated that adenosine deaminase stimulates release of neurotransmitter through a mechanism independent of depletion of adenosine. A possible direct action of adenosine deaminase should be taken into account when the enzyme is used to unmask the effects of endogenous adenosine
Specific binding sites for inositolhexakisphosphate in brain and anterior pituitary.
No full text[3H]Inositolhexakisphosphate (InsP6) binds to a single population of specific and saturable recognition sites in membranes prepared from cerebral hemispheres, anterior pituitaries, or cultured cerebellar neurons. Binding is temperature and pH dependent, exhibits slow association and dissociation kinetics, and differentiates among various inositolpolyphosphates (InsP6 is much more potent than inositol-1,3,4,5,6-pentakis- and inositol-1,3,4,5-tetrakisphosphate, whereas inositol-1,4,5-trisphosphate is inactive as a displacer). In membranes from cerebral hemispheres, saturation analysis reveals a KD value of 33 +/- 4 nM and a maximal density (Bmax) of 152 +/- 23 pmol/mg of protein. Both affinity and density of [3H]InsP6 binding are lower in membranes from anterior pituitaries. In cultured cerebellar neurons, micromolar concentrations of divalent cations enhance both [3H]InsP6 binding and InsP6-stimulated 45Ca2+ uptake, suggesting that activation of specific receptors may be involved in the stimulation of 45Ca2+ uptake produced by InsP6. These data support the recent view that InsP6, as other inositolpolyphosphates, may act as a signal molecule in excitable cells
Antidegenerative effects of Mg(2+)-valproate in cultured cerebellar neurons.
No full textWe have investigated in the present study the effect of Mg(2+)-valproate on necrotic degeneration induced by an excitotoxic insult in primary culture of cerebellar neurons, that is an homogeneous population of glutamatergic neurons. Mg(2+)-valproate protected cultures against glutamate-induced neurotoxicity, acting as an indirect N-methyl-D-aspartate (NMDA) receptor antagonist, thus reducing free radical formation and affecting the biochemical parameters (i.e. 45Ca(2+)-influx, cyclic GMP formation, inositol phospholipid hydrolysis and protein kinase C translocation) that undergo modifications following NMDA receptor activation in cerebellar granule cells
Effects of CDP-choline administration on receptor-stimulated inositol phospholipid hydrolysis in brain slices and neuronal cultures
No full text[No abstract available
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