Disease relevance of Synaptosomes

• The effects of experimental galactose toxicity on inositol and phosphatidylinositol (PtdIns) metabolism in synaptosomes from 0- to 30-day-old rats were investigated [1].
• Active, high-affinity, sodium-dependent uptake of gamma-aminobutyric acid and of the acidic amino acid D-aspartate was inhibited by pretreatment of synaptosomes with neuraminidase from Vibrio cholerae [2].
• Selective effects of hyperprolactinemia on in vitro dopamine release from median eminence synaptosomes [3].
• Tetanus toxin (100 nM) when preincubated with guinea pig cerebrocortical synaptosomes for 45 min reduces the final extent of the KCl-evoked, Ca(2+)-dependent, glutamate transmitter release to 30% of non-intoxicated controls [4].
• Chronic renal failure (CRF) is associated with a sustained rise in the concentration of cytosolic calcium [( Ca2+]i) of brain synaptosomes [5].

Psychiatry related information on Synaptosomes

• Lithium, carbamazepine, and partial sleep deprivation raised the levels of T(3) in synaptosomes of the amygdala [6].
• Phosphoinositide kinase activities in synaptosomes prepared from brains of patients with Alzheimer's disease and controls [7].
• In separate experiments, the pharmacological effects of RTI-55 were assessed biochemically by measuring uptake of dopamine in synaptosomes prepared from RTI-treated mice and behaviorally by monitoring locomotor activity [8].
• Dopaminergic system activity and cellular defense mechanisms in the striatum and striatal synaptosomes of the rat subchronically exposed to manganese [9].
• The action of suramin on apyrase activity in hippocampal synaptosomes and its effects on retention of inhibitory avoidance learning were evaluated [10].

High impact information on Synaptosomes

• Architecture of the gamma delta resolvase synaptosome: oriented heterodimers identity interactions essential for synapsis and recombination [11].
• The N-type Ca2+ channel blocker omega-conotoxin GVIA (omega-CgTx) suppresses the excitatory postsynaptic responses only partially, whereas potassium-induced release of glutamate from brain synaptosomes can be blocked by omega-Aga-VIA (ref. 9), a blocker of P-type calcium channels and possibly of other types of calcium channels [12].
• Here we report that inhibition of transmitter release from synaptosomes caused by botulinum neurotoxin A (BoNT/A) is associated with the selective proteolysis of the synaptic protein SNAP-25 [13].
• Calcium/calmodulin-dependent protein kinase II increases glutamate and noradrenaline release from synaptosomes [14].
• Here we report that the introduction of Ca2+/CaM-dependent PK II, autoactivated by thiophosphorylation, into rat brain synaptosomes (isolated nerve terminals) increases the initial rate of induced release of two neurotransmitters, glutamate and noradrenaline [14].

Chemical compound and disease context of Synaptosomes

• Tetanus toxin and botulinum toxins type A and B inhibit glutamate, gamma-aminobutyric acid, aspartate, and met-enkephalin release from synaptosomes. Clues to the locus of action [4].
• Material extracted and partially purified from plasma of the Sabra hypertension prone rats was found to be capable of 1) inhibiting the binding of 3H-ouabain to rat brain synaptosomes, 2) inhibiting the activity of rat brain microsomal Na, K activated adenosine triphosphatase, and 3) increasing the contractile force of rat heart muscle [15].
• Characterization of interactions of methylmercury with Ca2+ channels in synaptosomes and pheochromocytoma cells: radiotracer flux and binding studies [16].
• Glutamate transport activates in EAAC1-injected oocytes and C6 glioma have similar Km values for glutamate (Km = 15-24 microM) and Na+ (apparent Km = 35-50mM), and these values markedly differ from those observed in rat synaptosomes (glutamate, Km = 1-5 microM; Na+, Km = 13-20 mM) [17].
• Clostridium neurotoxins produce inhibition of both basal and K(+)-evoked serotonin release in rat brain synaptosomes [18].

Biological context of Synaptosomes

• Specific CAPS antibodies inhibit Ca2+-activated norepinephrine release from lysed synaptosomes that contain membrane-associated CAPS, indicating that membrane-bound CAPS is essential for neural DCV exocytosis [19].
• The phosphorylation of protein I, a specific neuronal protein, has been found to be regulated both by cyclic AMP (cAMP) and by calcium, in intact as well as in lysed synaptosome preparations from rat brain [20].
• Preliminary data from NaDodSO4/polyacrylamide gel electrophoresis studies after covalent binding of [3H]PCP to synaptosomes, suggest that the high-affinity binding site may be on a large protein (Mr approximately equal to 220,000) [21].
• It is postulated that there is a calcium-dependent mechanism in synaptosomes through which the function of the mitochondrial respiratory chain or of oxidative phosphorylation is stimulated directly without the involvement of either adenine nucleotides or mitochondrial dehydrogenases [22].
• Botulinum toxin type A blocks the morphological changes induced by chemical stimulation on the presynaptic membrane of Torpedo synaptosomes [23].

Anatomical context of Synaptosomes

• Glutamate and aspartate are known to be released in a calcium-dependent fashion by depolarizing stimulation of mammalian brain synaptosomes (isolated nerve endings), an observation which strengthens their claims to be neurotransmitter candidates [24].
• Spinal cord synaptosomes prepared from affected animals showed a significantly increased ability to accumulate [3H]glycine, indicating an increased capacity of the high-affinity neuronal uptake system for glycine [25].
• Investigating this possibility, we found ASIC in hippocampus, in synaptosomes, and in dendrites localized at synapses [26].
• Isolation of a presynaptic plasma membrane fraction from Torpedo cholinergic synaptosomes: evidence for a specific protein [27].
• When these synaptosomes were incubated in solutions containing Ca, ATP, and oxalate, electrondense Ca oxalate deposits were found in intraterminal mitochondria, SER cisterns, and large vesicular profiles [28].

Associations of Synaptosomes with chemical compounds

• Exocytotic release of glutamate from synaptosomes (isolated nerve terminals) has not been convincingly demonstrated, however, and remains highly controversial [29].
• In vitro studies support the excitatory effect and low doses of dopamine have been shown to release LH-RH from incubated hypothalamic fragments and synaptosomes [30].
• Selective release of newly synthesised and newly captured GABA from synaptosomes by potassium depolarisation [31].
• Choline biosynthesis by a preparation enriched in synaptosomes from rat brain [32].
• Co-release of glutamate and aspartate from cholinergic and GABAergic synaptosomes [24].

Gene context of Synaptosomes

• Furthermore, depletion of MARCKS by MARCKS-AON treatment of neurons resulted in a significant decrease in Ang II-stimulated accumulation of TH and DbetaH immunoreactivities and [3H]NE uptake activity in synaptosomes [33].
• Finally, in rat synaptosomes, both spectrin and NR2B are loosened from membranes upon addition of physiological concentrations of calcium ions [34].
• The purified synaptosomes exhibited specific enrichment of Rab3a, Rab5a, Ral, and several other GTPases [35].
• 2-Deoxy-d- [1-(14)C]glucose is significantly reduced in synaptosomes prepared from Igf1-/- brains, and the deficit is corrected by inclusion of Igf1 in the incubation medium [36].
• Subcellular fractionations of olfactory bulb synaptosomes, combined with chemical lesions of olfactory neurons, confirm the presence of Emx2 in axon terminals [37].

Analytical, diagnostic and therapeutic context of Synaptosomes

• We measured Na uptake under conditions of control, veratridine stimulation, and tetrodotoxin inhibition, in synaptosomes from normal and acutely uremic (blood urea nitrogen, 250 mg/dl) rats [38].
• The synaptosomes, prepared by discontinuous sucrose gradient centrifugation, were subjected to osmotic shock at pH 9.5 for 10--15 min and subfractionated on a discontinuous sucrose gradient [39].
• Western blot analysis of purified synaptosomes and homogenates from avian cerebellum revealed major immunoreactive proteins with molecular masses (130 kDa and 138 kDa) similar to those of purified erythrocyte PMCA [40].
• After discontinuous sucrose density gradient centrifugation of isotonic postnuclear particulate fractions, the bulk of Thy-1 was recovered in regions of the gradients containing synaptosomes [41].
• GABA-modulin (GM), a basic polypeptide purified from rat brain synaptosomes, which is an allosteric inhibitor of GABA recognition sites, has been detected in primary cultures of cerebellar interneurons enriched in granule cells by immunohistochemistry, using a specific antibody raised in rabbit injected with GM purified from rat brain synaptosomes [42].

References