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Biomedical subjects

M J Wolf

Publications and source records attributed to M J Wolf.

At least 19 recordsLinked to original sources
PubMed2002

Neurobehavioral and developmental profile of very low birthweight preterm infants in early infancy.

AIM: To describe the neurobehavioral and developmental profile of very low birthweight (VLBW) preterm infants in early infancy. METHODS: Twenty VLBW infants and 10 term control infants were assessed at term, 3 and 6 mo of age. Neurobehavioral assessments included the Neonatal Behavioral Assessment Scale (NBAS) at term; the Infant Behavioral Assessment at term, 3 and 6 mo of age and the Behavioral Rating Scale of the Bayley Scales of Infant Development-II (BSID-II) at 3 and 6 mo of age. Development was evaluated with the Bayley Motor and Mental Scale at 3 and 6 mo. RESULTS: At term age VLBW infants differed from term infants on all the clusters and supplementary items of the NBAS. VLBW infants also showed more stress and less approach behavior at term and 6 mo of age and more problems with self-regulation in all subsystems at 6 mo of age. Moreover, VLBW infants performed lower on the Bayley Motor, Mental and Behavioral Rating Scale: 12 VLBW infants scored questionable or non-optimal on the Psychomotor Development Index and 18 questionable or non-optimal on the Behavioral Rating Scale. These results support the need for neurobehavioral intervention of VLBW infants in the first 6 mo of life. CONCLUSION: Almost all VLBW infants showed non-optimal motor quality behavior at 6 mo and encountered far more problems with self-regulation compared with term infants.

Age Factors↗
PubMed2000

Identification of the calmodulin-binding domain of recombinant calcium-independent phospholipase A2beta. implications for structure and function.

Calcium-independent phospholipase A(2) (iPLA(2)) is the major phospholipase A(2) activity in many cell types, and at least one isoform of this enzyme class is physically and functionally coupled to calmodulin (CaM) in a reversible calcium-dependent fashion. To identify the domain in recombinant iPLA(2)beta (riPLA(2)beta) underlying this interaction, multiple techniques were employed. First, we identified calcium-activated CaM induced alterations in the kinetics of proteolytic fragment generation during limited trypsinolysis (i.e. CaM footprinting). Tryptic digests of riPLA(2)beta (83 kDa) in the presence of EGTA alone, Ca(+2) alone, or EGTA and CaM together resulted in the production of a major 68-kDa protein whose kinetic rate of formation was specifically attenuated in incubations containing CaM and Ca(+2) together. Western blotting utilizing antibodies directed against either the N- or C-terminal regions of riPLA(2)beta indicated the specific protection of riPLA(2)beta by calcium-activated CaM at a cleavage site approximately 15 kDa from the C terminus. Moreover, calcium-activated calmodulin increased the kinetic rate of tryptic cleavage near the active site of riPLA(2)beta. Second, functional characterization of products from these partial tryptic digests demonstrated that approximately 90% of the 68-kDa riPLA(2)beta tryptic product (i.e. lacking the 15-kDa C-terminus) did not bind to a CaM affinity matrix in the presence of Ca(2+), although >95% of the noncleaved riPLA(2)beta as well as a 40-kDa C-terminal peptide bound tightly under these conditions. Third, when purified riPLA(2)beta was subjected to exhaustive trypsinolysis followed by ternary complex CaM affinity chromatography, a unique tryptic peptide ((694)AWSEMVGIQYFR(705)) within the 15-kDa C-terminal fragment was identified by RP-HPLC, which bound to CaM-agarose in the presence but not the absence of calcium ion. Fourth, fluorescence energy transfer experiments demonstrated that this peptide (694) bound to dansyl-calmodulin in a calcium-dependent fashion. Collectively, these results identify multiple contact points in the 15-kDa C terminus as being the major but not necessarily the only binding site responsible for the calcium-dependent regulation of iPLA(2)beta by CaM.

Amino Acid Motifs↗
PubMed2000

TrExML: a maximum-likelihood approach for extensive tree-space exploration.

MOTIVATION: Maximum-likelihood analysis of nucleotide and amino acid sequences is a powerful approach for inferring phylogenetic relationships and for comparing evolutionary hypotheses. Because it is a computationally demanding and time-consuming process, most algorithms explore only a minute portion of tree-space, with the emphasis on finding the most likely tree while ignoring the less likely, but not significantly worse, trees. However, when such trees exist, it is equally important to identify them to give due consideration to the phylogenetic uncertainty. Consequently, it is necessary to change the focus of these algorithms such that near optimal trees are also identified. RESULTS: This paper presents the Advanced Stepwise Addition Algorithm for exploring tree-space and two algorithms for generating all binary trees on a set of sequences. The Advanced Stepwise Addition Algorithm has been implemented in TrExML, a phylogenetic program for maximum-likelihood analysis of nucleotide sequences. TrExML is shown to be more effective at finding near optimal trees than a similar program, fastDNAml, implying that TrExML offers a better approach to account for phylogenetic uncertainty than has previously been possible. A program, TreeGen, is also described; it generates binary trees on a set of sequences allowing for extensive exploration of tree-space using other programs. AVAILABILITY: TreeGen, TrExML, and the sequence data used to test the programs are available from the following two WWW sites: http://whitetail.bemidji.msus. edu/trexml/and http://jcsmr.anu.edu.au/dmm/humgen.+ ++html.

Algorithms↗
PubMed1999

Neurodevelopmental outcome at 1 year in Zimbabwean neonates with extreme hyperbilirubinaemia.

UNLABELLED: The study concentrates on estimating the magnitude of the effect of a single risk factor, maximum total serum bilirubin (TSB) in excess of 400 micromol/l (23.4 mg/dl), on the neurodevelopmental outcome of 50, singleton, Zimbabwean neonates at 1 year of age. At 1 year corrected age the Bayley Scales of Infant Development (BSID) was administered. Two infants died and five were lost to follow up. TSB was neither associated with birth weight nor with gestational age. Of 43 infants with a TSB > 400 micromol/l (23.4 mg/dl),11(26%) scored abnormal on the BSID at 1 year of age and 5 (12%) infants developed the choreoathetoid type of cerebral palsy. CONCLUSION: Infants with bilirubin levels between 400 and 500 micromol/l (23.4 and 29.2 mg/dl) who scored abnormal or suspect on the Bayley Scales of Infant Development were preterm or had haemolytic disease. All term infants without haemolysis and with bilirubin levels between 400 and 500 micromol/l (23.4 mg/dl-29.2 mg/dl) were normal at 1 year of age.

Analysis of Variance↗
PubMed1999

Acquired microcephaly after low Apgar score in Zimbabwe.

Serial head circumference measurements were made on 165 African babies born with a 5 min Apgar score of 5 or less. Measurements were taken at birth and at 4, 9, and 12 months of age. In the majority of infants the onset of microcephaly could be diagnosed as early as 4 months of age. Twenty-five of the 142 infants were microcephalic at 1 year. Neurological development was impaired in 19 of the 25 (76 per cent) microcephalic infants and in 18 of the 117 (15 per cent) normocephalic infants. Fourteen of the 16 (88 per cent) infants with severe quadriplegia developed microcephaly before the age of 4 months. A decreased rate of head growth during the first 4 months of life in African infants born with a low Apgar score correlates closely with the development of microcephaly. Infants with an acquired microcephaly have a high probability of developing neurologic impairment by the age of 1 year. Serial head circumference measurement in low Apgar score babies in developing countries is an easy, simple, and inexpensive method to detect microcephaly.

Analysis of Variance↗
PubMed1998

Neonatal neurological examination as a predictor of neuromotor outcome at 4 months in term low-Apgar-score babies in Zimbabwe.

The predictive value of the neonatal neurological examination (NNE) adapted from Prechtl, was investigated in 139 term Zimbabwean infants born with an Apgar score of five or less at 5 min. At 4 months, seven infants had died and 13 were lost to follow-up, leaving 119 infants to undergo the Infant Motor Screen (IMS). Eighty-eight infants were diagnosed as normal, six as suspect and 25 as abnormal at screening. The sensitivity, specificity, positive predictive value and negative predictive value of the NNE were 94%, 55%, 42% and 96%, respectively. Seventeen (14%) infants had developed microcephaly at 4 months and 13 (77%) of them scored abnormal on the IMS. Twenty-three of the 48 (48%) infants who had convulsions within 48 h of birth, were diagnosed as abnormal (P < 0.0001). The NNE proved to be very sensitive in detecting neurodevelopmental abnormalities in the neonatal period and the five abnormal syndromes derived from the NNE were able to correctly identify 94% of the abnormal infants.

Adolescent↗
PubMed1998

Neurological status in severely jaundiced Zimbabwean neonates.

Neurological status was studied in 50 jaundiced infants with a total serum bilirubin of > 400 mumol/l (23.4 mg/dl). Infants were assessed in the neonatal period with the Neonatal Neurological Examination and 4 months of age with the Infant Motor Screen. Twenty-six (52 per cent) infants were premature. Analysis of variance did not show a significant difference between gestational age, birth weight, and maximum total serum bilirubin or between gestational age, birth weight, and neurological optimality score. Based on the presence of abnormal neurological syndromes the infants were classified as normal (n = 27), suspect (n = 11), or abnormal (n = 12). Serum bilirubin levels were higher (p < 0.0001) and the neonatal neurological examination scores lower (p < 0.0001) in the seven (14 per cent) infants who received an exchange transfusion. In the transfused group four out of seven infants and in the non-transfused group seven out of 43 infants were classified as abnormal (p < 0.03). The Neonatal Neurological Examination was shown to be sensitive in detecting neurodevelopmental abnormalities in the neonatal period, with a sensitivity of 83 per cent, specificity of 88 per cent, positive predictive value of 62 per cent, and negative predictive value of 96 per cent.

Analysis of Variance↗
PubMed1998

The predictive value of developmental testing of extremely jaundiced African infants.

The predictive value of the Neonatal Neurological Examination (NNE) adapted from Prechtl (1977) and the Infant Motor Screen (IMS) from Nickel (1989) at 4 months was studied in severely jaundiced infants in Zimbabwe. Fifty infants were examined with the NNE, 41 with the IMS and 43 with the Bayley Scales of Infant Development (BSID) (Bayley 1969). Five infants had choreoathetosis and six had a motor delay at age 1 year. The NNE and IMS proved to be sensitive instruments particularly when two infants who became malnourished after the neonatal period were excluded. Logistic regression was used to investigate the relation between the BSID and five selected predictors from the NNE. This resulted in a correct classification of 93%. By using only the predictors acoustic blink and traction response, 80% of the infants were correctly classified but the number of false negatives was reduced from three to one.

Black People↗
PubMed1997

Glucose-responsitivity and expression of an ATP-stimulatable, Ca(2+)-independent phospholipase A2 enzyme in clonal insulinoma cell lines.

We have previously reported that pancreatic islet beta-cells and clonal HIT insulinoma cells express an ATP-stimulatable Ca(2+)-independent phospholipase A2 (ASCI-PLA2) enzyme and that activation of this enzyme appears to participate in glucose-stimulated insulin secretion. To further examine this hypothesis, glucose-responsitivity and expression of ASCI-PLA2 activity in various insulinoma cell lines were examined. Secretagogue-stimulated insulin secretion was observed with beta TC6-f7 and early passage (EP)-beta TC6 cells. In contrast, RIN-m5f, beta TC3, and late passage (LP)-beta TC6 cells exhibited little secretagogue-induced secretion. A haloenollactone suicide substrate (HELSS) which inhibits ASCI-PLA2 activity ablated secretagogue-induced insulin secretion from beta TC6-f7 and EP-beta TC6 cells. All insulinoma cell lines studied expressed both cytosolic and membrane-associated Ca(2+)-independent PLA2 activities which were inhibited by HELSS. The cytosolic enzymatic activity in the glucose-responsive beta TC6-f7 and EP-beta TC6 cells was activated by ATP and protected against thermal denaturation by ATP, but this was not the case in the glucose-unresponsive RIN-m5f, beta TC3, or LP-beta TC6 cells. Comparison of the distribution of Ca(2+)-independent PLA2 activity revealed that membrane-associated activity was higher than cytosolic activity in beta TC6-f7 and EP-beta TC6 cells but not in RIN-m5f, beta TC3, or LP-beta TC6 cells. Insensitivity of cytosolic activity to ATP may prevent association of the PLA2 activity with membrane substrates and contribute to attenuated glucose-responsitivity in the RIN-m5f, beta TC3, or LP-beta TC6 cells. HIT insulinoma cells were also found to undergo a decline in both glucose-responsitivity and membrane-associated Ca(2+)-independent PLA2 activity upon serial passage in culture, and this was associated with a reduction in membrane content of arachidonate-containing phospholipids. These and previous results suggest that the ATP-stimulatable PLA2 enzyme may participate in glucose-induced insulin secretion.

Adenosine Triphosphate↗
PubMed1997

Depletion of intracellular calcium stores activates smooth muscle cell calcium-independent phospholipase A2. A novel mechanism underlying arachidonic acid mobilization.

Herein we present multiple lines of evidence which demonstrate that depletion of internal calcium stores is both necessary and sufficient for the activation of calcium-independent phospholipase A2 during arginine vasopressin (AVP)-mediated mobilization of arachidonic acid in A-10 smooth muscle cells. First, AVP-induced [3H]arachidonic acid release was independent of increases in cytosolic calcium yet was decreased by pharmacological inhibition of the release of calcium ion from internal stores. Second, thapsigargin induced the dramatic release of [3H]arachidonic acid from A-10 cells at a similar rate as the AVP-induced release of arachidonic acid, and the release of arachidonic acid by either AVP or thapsigargin was entirely inhibited by (E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one (BEL). Third, the magnitude of thapsigargin-induced [3H]arachidonic acid release was entirely independent of alterations in cytosolic calcium concentration. Fourth, A23187 resulted in the BEL-inhibitable release of [3H]arachidonic acid from A-10 cells even when ionophore-induced increases in cytosolic calcium were completely prevented by calcium chelators. Fifth, pretreatment of A-10 cells with a calmodulin antagonist (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, HCl) resulted in the time-dependent decrease of subsequent thapsigargin-induced [3H]arachidonic acid release. Collectively, these results identify a novel paradigm which links alterations in calcium homeostasis to the calmodulin-mediated regulation of calcium-independent phospholipase A2 through the depletion of internal calcium stores.

Animals↗
PubMed1997

Extreme hyperbilirubinaemia in Zimbabwean neonates: neurodevelopmental outcome at 4 months.

UNLABELLED: As part of a prospective study of severely jaundiced Zimbabwean infants, the relationship between maximum total serum bilirubin (TSB) concentration in the neonatal period and neurodevelopmental outcome at the corrected age of 4 months was studied. Fifty infants with a TSB of > 400 micromol/l (23.4 mg/dl) were enrolled and screened with a neonatal neurological examination (NNE). The cause of jaundice was low birth weight in 22 (44%), ABO incompatability in 8 (16%), sepsis in 8 (16%) and congenital syphilis (6%) in 3 infants. In 9 infants a cause could not be determined. At 4 months, 2 infants had died and 3 were lost to follow up, leaving 45 infants for the infant motor screen (IMS) at 4 months of age. Mean TSB in the neonatal period was 485 micromol/l (28.2 mg/dl), and 7 infants received an exchange transfusion. Mean TSB of the infants with an exchange transfusion was 637 micromol/l (37.2 mg/dl) (range 429-865 micromol/l (25-50.3 mg/dl)) and of the infants without transfusion 459 micromol/l (26.8 mg/dl) (range 400 740 micromol/l (23.4-43 mg/dl)) (P < 0.0001). The TSB was not associated with birth weight, gestational age, gender or head circumference of the baby. On the IMS, 6 of 45 (13.3%) infants scored abnormal, 6 (13.3%) suspect and 33 (73%) scored normal. Three of the six (50%) remaining infants who received an exchange transfusion scored abnormal on the IMS while only 3 of the 39 (8%) infants without exchange transfusion were abnormal. CONCLUSION: More than 25% of infants with a TSB of > 400 micromol/l (23.4 mg/dl) scored abnormal or suspect at 4 months of age and half of these infants already showed irreversible neurological symptoms. All infants who scored abnormal or suspect on the IMS with bilirubin levels between 400 and 500 micromol/l (23.4 and 29.2 mg/dl) had haemolytic disease or were premature.

Bilirubin↗
PubMed1997

Neurological findings in neonates with low Apgar in Zimbabwe.

OBJECTIVES: Document neurological condition of African neonates with a low apgar score. SETTING: Mpilo Hospital, Bulawayo, Zimbabwe. SUBJECTS: 165 babies with an Apgar score of 5 or less at 5 min. METHODS: Neurological examination at term age according to Prechtl. Babies were classified as normal, suspect or abnormal and compared with two reference groups, one from Groningen, the Netherlands and one from Grenada in the Caribbean. RESULTS: A higher number of Zimbabwean babies were delivered by Caesarean section compared to the Groningen group (P < 0.001). Babies delivered by vacuum extraction scored significantly lower compared to babies delivered by Caesarean section (P < 0.003). Twenty abnormal signs derived from the neonatal neurological examination proved to be predictive on the total optimality score (P < 0.001). The number of infants who were classified as abnormal was higher in the Zimbabwean population (P < 0.01). CONCLUSION: The selected abnormal signs derived from the neonatal neurological examination proved to be highly predictive on the neurological condition. The neonatal morbidity in Zimbabwean neonates with a low Apgar score was higher when compared with two reference groups from Groningen and Grenada.

Adolescent↗
PubMed1997

Neurodevelopmental outcome in babies with a low Apgar score from Zimbabwe.

The early identification of neurological dysfunction in the neonatal period, the predictive value of single items of the neonatal neurological examination (NNE) adapted from Prechtl and the developmental outcome at 1 year of age in infants with a low Apgar score in Zimbabwe were studied. One hundred and sixty-five infants were examined with the NNE and 142 with the Bayley Scale of Infant Development (BSID) at 1 year of age. Twenty-three infants had cerebral palsy, ten had a motor delay or developmental delay, and four were mentally retarded. The NNE proved to be a sensitive instrument for detecting neurodevelopmental abnormality. Logistic regression analysis was used to investigate the relationship between the BSID and nine selected predictors from the NNE. This resulted in a correct classification of 94%. However, the number of false negatives was high. By using only the variability of movements and fixation as predictors the number of false negatives was reduced to one.

Apgar Score↗
PubMed1996

Expression, purification, and kinetic characterization of a recombinant 80-kDa intracellular calcium-independent phospholipase A2.

A CHO cell-derived 80-kDa recombinant polypeptide (GenBank number I15470I15470) putatively encoding a calcium-independent phospholipase A2 was expressed in S. frugiperda cells resulting in over a 15-fold increase in a calcium-independent phospholipase A1/A2 activity which was entirely inhibitable by (E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one. The recombinant polypeptide was purified from cytosol by sequential tandem affinity chromatographies employing ATP-agarose and calmodulin-Sepharose stationary phases. This strategy resulted in the rapid purification (36 h) of recombinant phospholipase A2 activity in 56% overall yield to a single intense 80-kDa protein band on SDS-polyacrylamide gel electrophoresis after silver staining. The purified protein possessed phospholipase A1, phospholipase A2, and lysophospholipase activities. Microbore anion exchange chromatography demonstrated that the 80-kDa protein band was comprised of multiple distinct isoforms including an anionic isoform which possessed over a 5-fold higher specific activity (5 micromol/mg.min) than earlier eluting isoforms. Collectively, these results unambiguously demonstrate that: 1) the 80-kDa polypeptide catalyzes phospholipase A1/A2 and lysophospholipase activities with distinct kinetic parameters; 2) calmodulin and ATP both interact with the catalytic polypeptide independent of regulatory proteins; and 3) distinct isoforms of this polypeptide exist which possess markedly different specific activities.

Animals↗
PubMed1996

The calcium-dependent association and functional coupling of calmodulin with myocardial phospholipase A2. Implications for cardiac cycle-dependent alterations in phospholipolysis.

Herein we demonstrate the calcium-dependent regulation of myocardial phospholipase A2 activity, which is mediated by a cytosolic protein constituent that can be chromatographically resolved from, and subsequently reconstituted with, purified myocardial phospholipase A2. Purification of this protein by sequential column chromatographies revealed an 18-kDa doublet, which was identified as calmodulin by Western blotting, calcium-dependent precipitation with W-7 agarose beads, and reconstitution of calcium-mediated phospholipase A2 inhibition with authentic homogeneous calmodulin. Calcium-induced calmodulin-mediated inhibition of myocardial phospholipase A2 was titrated by physiologic increments of calcium ion (Kd approximately 200 nM). Moreover, ternary complex affinity chromatography with calmodulin-Sepharose demonstrated that inhibition of myocardial phospholipase A2 activity by calmodulin resulted from the direct interaction of calmodulin with the myocardial phospholipase A2 catalytic complex. Exposure of cultured A-10 muscle cells to three structurally disparate calmodulin antagonists (W-7, trifluoperazine, and calmidazolium) resulted in the robust release of arachidonic acid, which was entirely ablated by pretreatment of cells with (E)-6-(bromomethylene)-3-(1-naphthalenyl)-2-H-tetrahydropyran-2-one. Collectively, this study identifies a novel mechanism whereby latent phospholipase A2 activity can be released from tonic inhibition by alterations in the interactions between the phospholipase A2 catalytic complex, calcium ion, and the intracellular calcium transducer, calmodulin.

Animals↗
PubMed1996

Evidence for association of an ATP-stimulatable Ca(2+)-independent phospholipase A2 from pancreatic islets and HIT insulinoma cells with a phosphofructokinase-like protein.

Glucose-induced insulin secretion from pancreatic islets requires metabolism of glucose within islet beta-cells, and ATP has attracted interest as a messenger of glucose metabolism within beta-cells. Glucose-induced insulin secretion from islets and HIT insulinoma cells is accompanied by activation of an ATP-stimulatable Ca(2+)-independent phospholipase A2 (ASCI-PLA2) enzyme, the catalytic activity of which resides in a 40 kDa protein. An analogous PLA2 enzyme in myocardium was recently found to consist of a complex of a 40 kDa catalytic protein with a tetramer of an isoform of the glycolytic enzyme phosphofructokinase (PFK). Association of the PFK isoform with the myocardial PLA2 catalytic protein was found to confer ATP sensitivity onto the enzyme complex. Here we demonstrate that the majority of HIT cell and islet ASCI-PLA2 catalytic activity elutes from a gel filtration column in a region corresponding to 400 kDa, suggesting that the 40 kDa beta-cell ASCI-PLA2 catalytic protein exists as part of a larger molecular mass complex. Islet and HIT cell ASCI-PLA2 activities were immunoprecipitated by antibodies directed against PFK, and the immunoprecipitates contained 40 and 85 kDa proteins which correspond to the molecular masses of the PLA2 catalytic protein and of a PFK monomer, respectively. Islet and HIT cell ASCI-PLA2 activities were selectively and reversibly adsorbed to affinity matrices containing immobilized PFK but not to similar matrices containing immobilized transferrin or bovine serum albumin. Addition of free PFK prevented binding of HIT cell ASCI-PLA2 activity to immobilized PFK matrices and promoted desorption of activity previously bound to such matrices. These results suggest that beta-cell ASCI-PLA2, like the myocardial enzyme, exists as a complex comprised of a catalytic protein and a PFK-like protein and raise the possibility that the ASCI-PLA2 complex may represent a component of the beta-cell glucose sensor, which links glycolysis, phospholipid hydrolysis, and membrane electrochemical events involved in glucose-induced insulin secretion.

Animals↗
PubMed1995

Long-term potentiation requires activation of calcium-independent phospholipase A2.

The predominant phospholipase activity present in rat hippocampus is a calcium-independent phospholipase A2 (302.9 +/- 19.8 pmol/mg.min for calcium-independent phospholipase A2 activity vs. 14.6 +/- 1.0 pmol/mg.min for calcium-dependent phospholipase A2 activity). This calcium-independent phospholipase A2 is exquisitely sensitive to inhibition by the mechanism-based inhibitor, (E)-6-(bromomethylene)-tetrahydro-3-(1-naphthalenyl)-2H-pyran -2-one (BEL). Moreover, treatment of hippocampal slices with BEL prior to tetanic stimulation prevents the induction of LTP (40.8 +/- 5.6% increase in excitatory post-synaptic potential (EPSP) slope for control slices (n = 6) vs. 5.8 +/- 8.5% increase in EPSP slope for BEL-treated slices (n = 8)). Importantly, LTP can be induced following mechanism-based inhibition of phospholipase A2 by providing the end product of the phospholipase A2 reaction, arachidonic acid, during the application of tetanic stimulation. Furthermore, the induction of LTP after treatment with BEL is dependent on the stereoelectronic configuration of the fatty acid provided since eicosa-5,8,11-trienoic acid, but not eicosa-8,11,14-trienoic acid, rescues LTP after BEL treatment (37.6 +/- 16.1% increase in EPSP slope for eicosa-5,8,11-trienoic acid vs. -3.7 +/- 5.2% increase in EPSP slope for eicosa-8,11,14-trienoic acid). Collectively, these results provide the first demonstration of the essential role of calcium-independent phospholipase A2 in synaptic plasticity.

Animals↗