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Biomedical subjects

A Lakatos

Publications and source records attributed to A Lakatos.

At least 19 recordsLinked to original sources
PubMed2006

Maternal separation alters serotonergic transporter densities and serotonergic 1A receptors in rat brain.

RATIONALE: The basic mechanisms underlying the association between early life maternal separation and adulthood psychiatric disorders are largely unknown. One possible candidate is the central serotonergic system, which is also abnormal in psychiatric illnesses. Neuroadaptational changes in serotonergic transporter and serotonergic 1A receptors may underlie links between early life stress and adulthood psychiatric disorders. OBJECTIVE: The aim of this study was to investigate the consequences of a rat model of maternal separation on serotonergic transporter and serotonergic 1A receptor densities and function in adult rat forebrain. METHODS: Rat pups were separated from dams from postnatal day 2 to postnatal day 14, each day, for zero time, 15 min and 180 min to determine the time-course of effects. A non-handled group was added to control for the effects of handling by an experimenter compared with the animal facility-reared group. Quantitative [(125)I]3beta-(4-iodophenyl)tropan-2beta-carboxylic acid methyl ester and [(125)I]-mPPI autoradiography was used to determine serotonergic transporter and serotonergic 1A densities, respectively. Adult rats were challenged with saline or serotonergic 1A agonist (+) 8-hydroxy-2-(di-n-propylamino)tetralin, 0.4 mg/kg, s.c.) and plasma adrenocorticotropic hormone and corticosterone were determined. RESULTS: serotonergic transporter and serotonergic 1A densities were significantly lower in the non-handled group in the paraventricular, arcuate, dorsomedial and ventromedial nuclei of the hypothalamus. The non-handled group also displayed lower serotonergic transporter and serotonergic 1A densities in the basolateral anterior, basolateral ventral and basomedial amygdaloid nuclei. Serotonergic transporter densities were also decreased in the CA3 area of the hippocampus in the non-handled group. In contrast, the maternal separation 15 min group displayed the highest serotonergic transporter and serotonergic 1A densities in the basomedial nucleus of amygdala, basolateral anterior nucleus of amygdala, basolateral ventral nucleus of amygdala and basomedial nucleus of amygdala amygdaloid nuclei. CONCLUSIONS: Early life maternal separation and the extent of handling can alter adult brain serotonergic transporter and serotonergic 1A levels and function in the forebrain. Alterations in these serotonergic systems by early rearing conditions might increase vulnerability for behavioral disorders in adulthood.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2006

Clinical canine spinal cord injury provides an opportunity to examine the issues in translating laboratory techniques into practical therapy.

STUDY DESIGN: Review. OBJECTIVES: To highlight the value of investigating the effects of putative therapeutic interventions in clinical spinal cord injury (SCI) in domestic dogs. SETTING: England, UK. METHODS: Many experimental interventions in laboratory rodents have been shown to ameliorate the functional deficits caused by SCI; the challenge now is to determine whether they can be translated into useful clinical techniques. Important differences between clinical SCI in human patients and that in laboratory rodents are in the size of the spinal cord and heterogeneity of injury severity. A further key issue is whether the statistical difference in outcome in the laboratory will translate into a useful difference in clinical outcome. Here, we stress the value of investigating the effects of putative therapies in clinical SCI in domestic dogs. The causes of injury, ability to categorise the severity and methods available to measure outcome are very similar between canine and human patients. Furthermore, postmortem tissue more rapidly becomes available from dogs because of their short lifespan than from human patients. RESULTS: The role that investigation of canine SCI might play is illustrated by our preliminary trials on intraspinal transplantation of olfactory glial cells for severe SCI. CONCLUSIONS: This canine translational model provides a means of 'filtering' putative treatments before human application.

Animals↗
PubMed2005

Nasal and frontal sinus mucosa of the adult dog contain numerous olfactory sensory neurons and ensheathing glia.

Olfactory glial cells have been the focus of much recent research interest because of their possible future use as cellular transplants in repair of spinal cord injury. Although olfactory glial cells can be collected from the olfactory bulb for in vitro culture, alternative sites would be preferable for safer surgical access. This study was designed to investigate the distribution of olfactory sensory neurons and olfactory glial cells within the canine peripheral olfactory system. Using immunohistochemistry and electron microscopy on perfused tissue we demonstrate that olfactory sensory neurons are found in both the caudal nasal and the frontal sinus epithelia. Olfactory ensheathing glia were found in the mucosa at both these sites implying that surgical access for harvesting cells for transplantation would be straightforward.

Animals↗
PubMed2002

CART promoter CRE site binds phosphorylated CREB.

It has been shown previously that: CART (cocaine- and amphetamine-regulated transcript) mRNA is tightly regulated in brain; protein kinase A (PKA) is involved in CART expression in GH3 cells; and a cyclic AMP-responsive element (CRE) site is present in the proximal promoter region of the CART gene. Thus, the goal of this study was to test if CRE binding protein (CREB) can bind to the consensus CRE site and if phosphorylation of CREB occurs in GH3 cells under conditions of enhanced CART gene expression. Electromobility shift assays showed that a 27-bp oligonucleotide containing the CART CRE site was indeed bound by nuclear factors. Western blotting showed that incubation of GH3 cells with forskolin, which enhances CART mRNA expression, caused an increase in phosphorylated CREB (P-CREB) levels. Supershift analyses indicated that the CART CRE oligo/protein complex interacted with a P-CREB antibody. Taken together, these data indicate that P-CREB is a likely regulator of CART expression in GH3 cells.

Animals↗
PubMed2002

Cryopreserved cells isolated from the adult canine olfactory bulb are capable of extensive remyelination following transplantation into the adult rat CNS.

Naturally occurring spinal cord injury in dogs provides a potentially powerful intermediate model for testing the efficacy of therapeutic strategies developed in experimental rodent models before phase 1 trials in human patients. A particularly promising strategy involves transplantation of olfactory ensheathing cells (OECs) that both promote axon regeneration and generate new myelin sheaths. As a first step in developing OEC transplantation in the canine intermediate model we describe the isolation, purification, and characterization of OECs from adult dog olfactory bulb. We also show that the canine OEC behaves in a manner similar to its rodent counterpart following transplantation into demyelinating lesions in rat spinal cord and that these properties are retained following cryopreservation.

Animals↗
PubMed2001

Gap junctional communication and connexin expression in cultured olfactory ensheathing cells.

The olfactory ensheathing cell (OEC) is a unique glial cell able to support neurite outgrowth in the CNS throughout life. The OEC has been described as having both Schwann cell-like and astrocyte-like characteristics. The purpose of this study was to compare gap junctional communication and connexin (Cx) expression in cultured olfactory ensheathing cells with both astrocytes and Schwann cells to establish which of these two cells types they most closely resemble. We examined the Cx mRNA profile of OECs, astrocytes, and Schwann cells using primers to Cx26, Cx32, Cx37, Cx43, Cx46, and Cx50. All connexins tested except Cx50 were expressed by all three cell types when initially cultured. However, we observed differences in the levels of expression of Cx32 and Cx26 between astrocytes, Schwann cells, and OECs that became pronounced with time. All three cell types show limited and variable gap junctional communication in culture as assessed by the transfer of microinjected Lucifer yellow. OECs had limited coupling compared with Schwann cells and astrocytes, although the extent of the dye spread through OECs was more comparable to that seen with Schwann cells than astrocytes. Thus, OECs display a profile of Cx expression that more closely resembles the Cx expression of Schwann cells rather than astrocytes.

Animals↗
PubMed2001

Synthesis, pH-dependent structural characterization, and solution behavior of aqueous aluminum and gallium citrate complexes.

Reactions of Al(III) and Ga(III) with citric acid in aqueous solutions, yielded the complexes (NH(4))(5)[M(C(6)H(4)O(7))(2)].2H(2)O (M(III) = Al (1), Ga (2)) at alkaline pH, and the complexes (Cat)(4)[M(C(6)H(5)O(7))(C(6)H(4)O(7))].nH(2)O (M(III) = Al (3), Ga (4), Cat. = NH(4)(+), n = 3; M(III) = Al (5), Ga (6), Cat. = K(+), n = 4) at acidic pH. All compounds were characterized by spectroscopic (FT-IR, (1)H, (13)C, and (27)Al NMR, (13)C-MAS NMR) and X-ray techniques. Complex 1 crystallizes in space group P1, with a = 9.638(5) A, b = 9.715(5) A, c = 7.237(4) A, alpha = 90.96(1) degrees, beta = 105.72(1) degrees, gamma = 119.74(1) degrees, V = 557.1(3) A(3), and Z = 1. Complex 2 crystallizes in space group P1, with a = 9.659(6) A, b = 9.762(7) A, c = 7.258(5) A, alpha = 90.95(2) degrees, beta = 105.86(2) degrees, gamma = 119.28(1) degrees, V = 564.9(7) A(3), and Z = 1. Complex 3 crystallizes in space group I2/a, with a = 19.347(3) A, b = 9.857(1) A, c = 23.412(4) A, beta = 100.549(5) degrees, V = 4389(1) A(3), and Z = 8. Complex 4 crystallizes in space group I2/a, with a = 19.275(1) A, b = 9.9697(6) A, c = 23.476(1) A, beta = 100.694(2) degrees, V = 4432.8(5) A(3), and Z = 8. Complex 5 crystallizes in space group P1, with a = 7.316(1) A, b = 9.454(2) A, c = 9.569(2) A, alpha = 64.218(4) degrees, beta = 69.872(3) degrees, gamma = 69.985(4) degrees, V = 544.9(2) A(3), and Z = 1. Complex 6 crystallizes in space group P1, with a = 7.3242(2) A, b = 9.4363(5) A, c = 9.6435(5) A, alpha = 63.751(2) degrees, beta = 70.091(2) degrees, gamma = 69.941(2) degrees, V = 547.22(4) A(3), and Z = 1. The crystal structures of 1-6 reveal mononuclear octahedral complexes of Al(III) (or Ga(III)) bound to two citrates. Solution NMR, on both 4- and 5- species, reveals rapid intramolecular exchange of the bound and unbound terminal carboxylates. Upon dissolution in water, the complexes, through a complicated reaction cascade, transform to oligonuclear 1:1 species that, in agreement with previous studies, represent the thermodynamically stable state in solution. The data provide, for the first time, structural details of low MW, mononuclear complexes of Al(III) (or Ga(III)) with citrate that are dictated, among other factors, by pH. The properties of 1-6 may provide clues relevant to their biological association with humans.

Aluminum↗
PubMed2001

Complexes of aluminium(III) with glucose-6-phosphate in aqueous solutions.

The interaction of aluminium(III) with glucose-6-phosphate (GP: LH2) in aqueous solutions has been studied from pH 1 to pH 8, by pH-potentiometry and multinuclear (31P, 27Al, 13C) NMR spectroscopy. Various mononuclear species (MLH2, MLH, ML, ML2H, ML2 and MLH(-3)) and dinuclear complexes M2L2H-n (n=1-4) are formed in the system. NMR clearly indicates that GP is already bound to Al(III) at pH 1. The potentiometric speciation results are confirmed and completed by spectroscopic experiments. Many peaks are observed in the 31P NMR spectra suggesting the formation of isomeric species. An attempt to assign the signals to the corresponding complexes is made, allowing a discussion about their structure. Interestingly enough no metal ion-induced deprotonation and coordination of the alcoholic-OH functions have been observed.

Aluminum↗
PubMed2000

Olfactory ensheathing cells and Schwann cells differ in their in vitro interactions with astrocytes.

Transplanted olfactory ensheathing cells (OECs) are able to remyelinate demyelinated axons and support regrowth of transected axons after transplantation into the adult CNS. Transplanted Schwann cells (SCs) share these repair properties but have limitations imposed on their behavior by the presence of astrocytes (ACs). Because OECs exist alongside astrocytes in the olfactory bulb, we have hypothesized that they have advantages over SCs in transplant-mediated CNS repair due to an increased ability to integrate and migrate within an astrocytic environment. In this study, we have tested this hypothesis by comparing the interactions between astrocytes and either SCs or OECs, using a range of in vitro assays. We have shown that (1) astrocytes and SCs segregate into defined non-overlapping domains in co-culture, whereas astrocytes and OECs freely intermingle; (2) both SCs and OECs will migrate across astrocyte monolayers, but only OECs will migrate into an area containing astrocytes; (3) SCs spend less time in contact with astrocytes than do OECs; and (4) astrocytes undergo hypertrophy when in contact with SCs, but not with OECs. Expression of N-cadherin has been implicated as a key mediator of the failure of SCs to integrate with astrocytes. However, we found no differences in the intensity of N-cadherin immunoreactivity between SCs and OECs, suggesting that it is not the adhesion molecule that accounts for the observed differences. In addition, the number of astrocytes expressing chondroitin sulfate proteoglycans (CSPG) is increased when astrocytes are co-cultured with Schwann cells compared with the number when astrocytes are grown alone or with OECs. Taken together, these data support the hypothesis that OECs will integrate more extensively than Schwann cells in astrocytic environments and are therefore better candidates for transplant-mediated repair of the damaged CNS.

Animals↗
PubMed1997

Effect of the lack of light impulses on the hypothalamic PACAP and C-fos immunoreactivities in rats.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a member of the secretin family. It is widely distributed in the central and peripheral nervous systems. The highest concentration of PACAP was found in the hypothalamus. In the present work it has been studied whether PACAP is involved in the mediation of photic stimuli to the anterior pituitary gland. We have examined the effect of the lack of light impulses on the hypothalamic PACAP and C-fos immunoreactivities. In adult rats 10 days after the removal of the eyes (surgical enucleation) and in those received monosodium glutamate treatment neonatally (chemical enucleation). The PACAP immunostaining enhanced in the hypothalamic magnocellular nuclei and in the extemal zone of the median eminence. C-fos immunoreactivity also enhanced in a few hypothalamic nuclei 2 hours after the surgical enucleation indicating that the lack of light impulses activated hypothalamic neurons which, in turn, might stimulate the release of PACAP into the portal circulation. It has been concluded that PACAP may be involved in photoendocrine regulations.

Animals↗
PubMed1996

New aspects of the neuroendocrine role of PACAP.

The presence of PACAP was revealed in the anterior pituitary with RIA, HPLC, and with the demonstration of its mRNA. The level of PACAP mRNA in the anterior pituitary is the highest during the proestrous LH surge. In our immunohistochemical studies we were able to demonstrate PACAP immunoreactive cells in the anterior pituitary. The shape and the distribution of PACAP immunoreactive cells were very similar to that of the gonadotropes; however, the number of PACAP cells was less than that of LH cells. Additionally, another PACAP-positive cell population with small diameter appeared in the proestrous stage, during pregnancy and lactation. Double labeling revealed that the major part of large PACAP cells exhibited LH immunoreactivity and those with a small diameter contained PRL. It is not clear whether the pituitary- or the hypothalamic-born PACAP, or both, influence pituitary LH and PRL secretion. I.c.v. administration of PACAP just prior to the critical period in the proestrous stage inhibited the expected ovulation and blocked the proestrus LH and PRL surge, although i.v. administration of PACAP had no effect. PACAP antiserum did not interfere with ovulation when i.c.v. or i.v. injection was used. Our results support the view that PACAP has a role in the control of LH and PRL secretion during the estrous cycle, pregnancy, and lactation. The inhibitory effect of PACAP on ovulation is mediated through the hypothalamus.

Animals↗
PubMed1996

PACAP participates in the regulation of the hormonal events preceeding the ovulation.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a member of the secretin family. It was isolated and characterized in 1989. Its neuroendocrine role was demonstrated in vivo and in vitro systems. It seems that in vivo the effect of PACAP on the gonadotrop hormone secretion depends on the route of administration. It was reported that intravenous (i.v.) injection of PACAP elevated, while intra-cerebro-ventricular (i.c.v.) administration depressed plasma LH levels. In the present study it was demonstrated that PACAP, administered i.c.v. before the critical period of the proestrous stage, blocked the ovulation and prevented the proestrous LH surge in rats. The blocking effect of PACAP is not directly mediated by endogenous opioids because the antagonizing effect of Naloxone, an opioid receptor antagonist, was questionable. Under our experimental conditions we could not confirm the stimulating effect of i.v. administered PACAP.

Animals↗
PubMed1994

Differences in nonenzymatic glycation of histones.

Time course of glucose binding by histone Hl and total histones was followed in isolated histone preparations and in thymus nuclei. In both cases the uptake of glucose by Hl was surprisingly high in contrast to a much lower uptake of glucose by total histones. DNA is not implicated in glycation of histones in nuclei.

Animals↗
PubMed1994

The kinetics of the addition of glucose and acetaldehyde to histone proteins.

The time-course of the reaction of H1 and total histone with glucose, acetaldehyde or both has been studied using the NBT reduction test and fluorescence. With both methods, purified H1 histone gave higher absorbance with acetaldehyde than with a 1:1 combination of glucose and acetaldehyde. For total histone, the opposite was found; a 1:1 combination of the above two aldehydes had the higher absorbance. As an explanation, the possibility of different reactivity of the amino groups with glucose and acetaldehyde is proposed. A possible simultaneous interaction between glucose, acetaldehyde and serum protein, mainly albumin, may alter the results of the diagnostic protein glycation methods, e.g. of the fructosamine test, and, therefore, also the monitoring of diabetes.

Acetaldehyde↗
PubMed1993

Non-enzymatic glycation of histones.

2-(2-Furoyl)-5-(2-furanyl)-1H-imidazole (FFI) is detected in total histones and the lysine-rich histone 1 fraction isolated from calf thymus after in vitro glycation and hydrolysis with HCl, using gas chromatographic/mass spectrometric analysis. The finding suggests that glucose is bound to the epsilon-amino groups of the lysine residues of the histones. No FFI is monitored in native histone samples.

Animals↗