RESUMEN
Magnetic circular dichroism spectra are reported for the compound I species of beef liver catalase (hydrogen-peroxide: hydrogen-peroxide oxidoreductase, EC 1.11.1.6) and horseradish peroxidase (donor: hydrogen-peroxide oxidoreductase, EC 1.11.1.7) and the pi cation radical derivatives of porphyrins that have been suggested as models of the electronic configuration of the heme in the compound I species of these enzymes. Comparison of the magnetic circular dichroism spectra of the compound I species with the spectra of [Co(octaethylporphyrin)]2Br and [Co(octaethylporphyrin)]2ClO4 indicates that in both the intermediate enzyme species the heme has been oxidized to a pi cation radical. While there is a clear distinction between the magnetic circular dichroism spectra of the 2A2u porphyrin [Co(III)octaethylporphyrin]2ClO4, and the 2A1u porphyrin, [Co(III)octaethylporphyrin]2Br, such specific differences are not observed in the spectra of the two enzymes. Analysis of our data suggests that the ground states in the two enzymes are far more similar than the ground states in the two model porphyrins.
Asunto(s)
Catalasa/metabolismo , Peroxidasa de Rábano Silvestre/metabolismo , Hígado/enzimología , Peroxidasas/metabolismo , Animales , Cationes , Bovinos , Fenómenos Químicos , Química , Dicroismo Circular , Cobalto , Radicales Libres , Hemo , Magnetismo , Conformación Molecular , PorfirinasRESUMEN
Absorption and magnetic circular dichroism spectra of native catalase, compound I and compound II have been measured and the data compared with that observed previously for horseradish peroxidase. The native catalase data at pH 6.9 are characteristic of a high-spin ferric porphyrin and are similar to the data reported for the ferric myoglobin and ferric horseradish peroxidase at pH 7. Oxidation of native catalase by peroxoacetic acid forms the compound I species that is identified by its low absorbance in the 400 nm Soret region and a series of overlapping bands between 450 nm and 680 nm. The magnetic circular dichroism spectra of compound I of catalase closely resembles that previously obtained for horseradish peroxidase compound I. These results indicate that the ground state of the heme pi-system is the same in both catalase and horseradish peroxidase compound I species. The compound II data show that the ratio of the magnetic circular dichroism intensity for the Soret to alpha A terms is 0.5 which means that there is a redistribution of angular momentum between the pi* excited states that give rise to the Soret and alpha-bands compared with the horseradish peroxidase compound II data where the ratio of the analogous A term intensities has a value of about 3. In addition, the magnetic CD spectra of both the catalase and horseradish peroxidase compound II species are reminiscent of typical metalloporphyrin spectra which lack charge-transfer transitions and where the metal d-orbitals are decoupled from the porphyrin pi-system.
Asunto(s)
Catalasa , Animales , Bovinos , Fenómenos Químicos , Química , Dicroismo Circular , Peróxido de Hidrógeno , MagnetismoRESUMEN
Absorption, circular dichroism (CD) and magnetic circular dichroism (MCD) spectra of beef liver catalase at pH 5.0 and 6.9, and its complexes with NaF, KCNO, NaCNS, NaN3 and NaCN, have been measured between 250 nm and 700 nm at room temperature. The pH 6.9 native catalase MCD shows the presence of several additional transitions not resolved in the absorption spectrum. While these bands can be seen in the spectra of all the derivatives, with the exception of the cyanide, their relative intensities changes considerably between complexes. Of special interest in the MCD of ferric hemes is the signal intensity at about 400 nm and 620 nm. The data indicate that the MCD intensity at 620 nm increases as the high spin iron porphyrin fraction increases, reaching a maximum with the fluoride complex. The 430 nm band intensity increases as the proportion of low spin iron increases, reaching a maximum with the cyanide complex. The MCD spectra also indicate clearly the existence of spin mixtures in the complexes with CNO-, CNS-, and N3-, where both the 430 nm and 620 nm bands have appreciable intensity. It is significant that despite almost identical absorption spectra the CNS- complex has higher fraction of low spin iron than either the CNO- or the N3- species. The differences between the pH 5 and 6.9 MCD spectra of the native catalase suggest that the environment of the heme centre is sensitive to protonation.
Asunto(s)
Catalasa/análisis , Hígado/enzimología , Animales , Bovinos , Dicroismo Circular , Hemo , Concentración de Iones de Hidrógeno , Espectroscopía de Resonancia Magnética , EspectrofotometríaRESUMEN
1. Low temperature magnetic circular dichroism spectra of high and low spin derivatives of metmyoglobin and myoglobin have been measured in the Soret and high wavelength regions. 2. The large difference in intensity of the Soret magnetic circular dichroism bands suggest that a correlation exists between the signal intensity and spin state of the heme-iron. 3. From a comparison of the high and low spin sepctra of the myoglobin derivatives it is concluded that oxymyoglobin contains between 10 and 20% of a ferrous high spin component below 100 degrees K.
Asunto(s)
Mioglobina , Animales , Dicroismo Circular , Frío , Compuestos Férricos , Caballos , Magnetismo , Miocardio , Potasio , Conformación Proteica , SodioRESUMEN
The absorption, circular dichroism (CD) and magnetic circular dichroism (MCD) spectra of native rat liver and crab (Scylla serrata) Cd,Zn-metallothionein have been measured and the data are compared. The MCD data indicate that there are close similarities in the geometries of the cadmium-binding sites in both of these proteins; however, the CD spectra are quite different for the rat liver and crab proteins. The CD spectrum for the crab metallothionein is unlike any previously reported for a cadmium-containing metallothionein. This suggests that the CD spectrum is sensitive to the different bridging pattern used in the binding sites in the crab compared with the rat-liver metallothionein. Cadmium binding to the metal-free metallothionein is demonstrated for both proteins and it is shown that there are only minor structural differences between the native and remetallated proteins. The structural changes that occur near to the cadmium-binding sites during cadmium loading to the native proteins have been followed using absorption and CD spectroscopy. Marked changes are observed in the CD spectrum which can be associated with a two-phase reaction: initially Zn2+ is displaced by the Cd2+, then at higher concentrations of Cd2+ the tetrahedral geometry of the Cd2+-binding sites is lost as more Cd2+ is bound using the same thiolate groups. While this latter reaction results in considerable change to the CD spectrum, only minor changes are observed in the absorption spectrum. A significant red shift is observed in the S leads to Cd charge transfer transition region of the MCD spectrum (230-270 nm) following both cadmium loading of native rat liver, Cd,Zn-metallothionein and the metallation of metal-free metallothionein with cadmium. There are two contributions to this effect in Cd,Zn-metallothionein: (i) there is a S leads to Zn band underlying the S leads to Cd band; and (ii) the occupation of zinc sites by cadmium changes the energy of the S leads to Cd transition.
Asunto(s)
Hígado/análisis , Metalotioneína , Animales , Braquiuros , Cadmio/metabolismo , Dicroismo Circular , Concentración de Iones de Hidrógeno , Magnetismo , Masculino , Metalotioneína/metabolismo , Ratas , Ratas EndogámicasRESUMEN
We report the first use of an emission probe based on the Cu(I)-thiolate chromophore, for the direct observation of copper metallothionein located in samples of rat liver. Elevated synthesis of Cu-MT in the rat liver was induced by subcutaneous injections of a series of aqueous CuCl2 solutions containing increasing amounts of Cu(II). Luminescence intensity in the 600 nm region, detected from frozen solutions of Cu-MT and from slices of the liver frozen at 77 K, following excitation in the 300 nm region, was dependent on the concentration of the Cu(II) used in the inducing solution. No such luminescence intensity was found for control samples obtained from the livers of rats not exposed to copper salts. It is suggested that this new method will allow direct visualization of Cu-MT in tissue where genetic disorders impare copper metabolism.
Asunto(s)
Cobre/análisis , Hígado/análisis , Metalotioneína/análisis , Animales , Cobre/metabolismo , Degeneración Hepatolenticular , Humanos , Luminiscencia , Ratas , Análisis EspectralRESUMEN
We report the observation of emission intensity at 77 K that is a function of Ag(I)-thiolate bonds formation within the protein metallothionein. The emission characteristics (a large, 250 nm, Stokes shift and long emission lifetime) suggests that the transition occurs from the excited triplet state. The emission intensity and circular dichroism both indicate that silver(I) clusters form with stoichiometric ratios of 12 Ag(I) to the 20 thiolate sulfur groups that are present in the protein. These data are the first to show that Ag(I)-metallothionein complexes are luminescent and that a specific Ag12-MT species forms.
Asunto(s)
Metalotioneína , Plata , Animales , Hígado , Luminiscencia , Conejos , Análisis EspectralRESUMEN
We studied the utility and limitations of conventional cerebral angiography in 25 patients with cerebral infarction unassociated with extracranial cerebrovascular disease during a 7-year period. In only one-third of cases was the angiogram diagnostic, and in a single case it altered the pre-angiogram diagnosis by revealing a previously unsuspected embolus. Among the cases clinically diagnosed as cerebral emboli, the 2 confirmatory angiograms were performed early (within 48 hours), and demonstrated medium-large or large vessel filling defects. Two-thirds of the negative angiograms in the embolic clinical category were delayed, but there was no statistically relevant predilection for specific vessel size involvement. The category, primary cerebral vasculopathy, comprised the largest group, 10 in all, and one-half had angiographic confirmation despite time delays. Angiographic recognition was dependent on a characteristic picture of vascular involvement, and not on timing or vessel size predilection. Mitral valve prolapse figured prominently in the clinical cases of vasculopathy of uncertain etiology, which contained a total of 4 cases. The 3 cases with nondiagnostic angiograms were all delayed and demonstrated nonspecific radiographic changes. Clinically, these cases demonstrated signs or symptoms of autoimmune dysfunction, raising the specter of primary cerebral vasculopathy as a cause of cerebral infarction, in contrast to recurrent cerebral emboli.
Asunto(s)
Angiografía Cerebral , Infarto Cerebral/diagnóstico por imagen , Adulto , Infarto Cerebral/etiología , Trastornos Cerebrovasculares/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Humanos , Embolia y Trombosis Intracraneal/diagnóstico por imagen , Masculino , Prolapso de la Válvula Mitral/complicaciones , Estudios RetrospectivosRESUMEN
Hypoxia decreases acetylcholine (ACh) synthesis and release in vitro, and ACh synthesis in vivo; however, its effect on extracellular concentration of ACh in vivo is not known. The calcium channel blocker nimodipine is a cerebrovascular dilator which also increases extracellular ACh in vivo. Therefore, it may provide protection from the effects of hypobaric hypoxia on the cholinergic system either via its effects on vascular function or by direct action on the nervous system. This study examined the effect of hypobaric hypoxia on extracellular ACh and choline levels, as measured by microdialysis, as well as the effects of nimodipine under hypoxia. Microdialysis guide cannulae were implanted into the hippocampal region of male Fischer rats so that probes would sample from the CA1 and DG regions. Animals were then exposed for eight hours to a simulated altitude of 5,500 m (18,000 ft) or tested at sea level for an equivalent duration. HPLC with electrochemical detection was used for analysis of the dialysates. At 5,500 m extracellular ACh levels in the placebo-treated group were significantly lower than the sea level group values. This decrement was reversed by nimodipine administered i.p. immediately preceding altitude ascent (10 mg/kg) and 250 min post-altitude ascent (10 mg/kg). These data suggest that nimodipine may provide protection from the detrimental effects of hypoxia on hippocampal cholinergic function.
Asunto(s)
Acetilcolina/metabolismo , Mal de Altura/metabolismo , Hipocampo/efectos de los fármacos , Hipoxia Encefálica/metabolismo , Nimodipina/farmacología , Animales , Hipocampo/metabolismo , Masculino , Microdiálisis , Ratas , Ratas Endogámicas F344RESUMEN
We report the case of a patient with the unusual combination of migraine, chorea, and retinal arterial thrombosis along with laboratory evidence of autoimmunity. In the absence of systemic lupus erythematosus, the clinical manifestations suggest the presence of the primary antiphospholipid antibody syndrome.
Asunto(s)
Autoanticuerpos/inmunología , Corea/complicaciones , Trastornos Migrañosos/complicaciones , Fosfolípidos/inmunología , Oclusión de la Arteria Retiniana/complicaciones , Adulto , Humanos , Masculino , SíndromeRESUMEN
Extracellular levels of dopamine (DA) and its metabolites (DOPAC and HVA) were monitored in the striatum of rats using in vivo microdialysis, in an attempt to elucidate the mechanism of cyclo (His-Pro) (histidyl-proline-diketopiperazine, CHP) on dopaminergic activity. Pretreatment with CHP (0.5 mg/kg SC) (n = 5) or the equivalent volume of saline (n = 5) was followed 30 min later by 5 mg/kg IP of d-amphetamine. Dialysate samples were collected and analyzed by high performance liquid chromatography with electrochemical detection (HPLC-EC). Following the initial increase in DA caused by d-amphetamine, DA levels of CHP-treated rats were significantly lower than saline-treated rats across time (p less than 0.05). No difference was observed for DOPAC or HVA. It is therefore unlikely that CHP interferes with the d-amphetamine-induced inhibition of DA reuptake. Other neurotransmitter systems may be involved in the CHP-induced augmentation of amphetamine's behavioral effects. Our data, as well as previous findings, suggest that attenuation of the dopaminergic response to d-amphetamine might be best explained on the basis of striatal DA depletion, possibly via tyrosine hydroxylase (TH) inhibition. This study also indicates that a dissociation may exist between the behavioral and the striatal DA response to acute amphetamine. The data support the hypothesis that amphetamine releases DA from a newly synthesized, extravesicular cytoplasmic pool, and that intracellular striatal DA is present in considerable excess relative to the extracellular DA.
Asunto(s)
Antioxidantes/farmacología , Cuerpo Estriado/metabolismo , Dextroanfetamina/farmacología , Dopamina/metabolismo , Péptidos Cíclicos/farmacología , Piperazinas/farmacología , Ácido 3,4-Dihidroxifenilacético/metabolismo , Animales , Cuerpo Estriado/efectos de los fármacos , Diálisis/métodos , Interacciones Farmacológicas , Ácido Homovanílico/metabolismo , Cinética , Masculino , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
Previous studies suggest that m2 muscarinic receptors serve as presynaptic autoreceptors. Blocking these receptors by selective antagonists may, therefore, lead to increased acetylcholine (ACh) release. This study assessed changes in extracellular ACh levels, via in vivo microdialysis, following administration of the m2 antagonist methoctramine. Drug or placebo (Ringer's solution) was perfused via a microdialysis probe into the CA1 hippocampal region of unrestrained, awake male Fischer rats. HPLC-EC was used for online analysis of the dialysates. Methoctramine significantly enhanced ACh release in a dose-dependent fashion as compared to placebo for the doses employed (0.25-16 microM). The present in vivo data corroborate studies that show increased ACh levels in vitro following application of m2 antagonists.
Asunto(s)
Acetilcolina/metabolismo , Diaminas/farmacología , Hipocampo/metabolismo , Parasimpatolíticos/farmacología , Análisis de Varianza , Animales , Relación Dosis-Respuesta a Droga , Espacio Extracelular/efectos de los fármacos , Espacio Extracelular/metabolismo , Hipocampo/efectos de los fármacos , Cinética , Masculino , Microdiálisis , Ratas , Ratas Endogámicas F344 , Técnicas Estereotáxicas , Factores de TiempoRESUMEN
There is evidence that muscarinic receptors of the M2 subtype are presynaptic autoreceptors that modify the release of acetylcholine (ACh) through a negative feedback mechanism. Blocking these receptors by selective antagonists may therefore lead to increased ACh release. This in vivo microdialysis study examined the effects of three M2 antagonists, AF-DX 116, AF-DX 384, and AQ-RA 741, on hippocampal cholinergic neurotransmission. Drug (2, 4, 8, or 16 microM) or vehicle (Ringer's solution) was perfused via a microdialysis probe into the CA1 hippocampal region of conscious male Fischer 344 rats. Levels of ACh and choline were assessed by HPLC-EC. When the dose was expressed in K1 multiples, all drugs (except AQ-RA 741 at the two highest concentrations) were found to be on the same linear dose-response curve. Choline levels were not affected by drug administration. All three compounds elevated ACh levels in a similar K1-normalized dose-response fashion, strongly supporting the concept that the proposed presynaptic mechanism of action is indeed based on the same M2 receptor. Such elevations of ACh may not only improve performance on memory tasks, but may also have therapeutic advantages in conditions of cholinergic hypofunction, such as Alzheimer's disease.
Asunto(s)
Acetilcolina/metabolismo , Hipocampo/metabolismo , Antagonistas Muscarínicos/farmacología , Animales , Barrera Hematoencefálica/efectos de los fármacos , Colina/metabolismo , Cromatografía Líquida de Alta Presión , Electroquímica , Espacio Extracelular/efectos de los fármacos , Espacio Extracelular/metabolismo , Hipocampo/efectos de los fármacos , Masculino , Microdiálisis , Ratas , Ratas Endogámicas F344 , Técnicas EstereotáxicasRESUMEN
Absorption, circular dichroism (CD), magnetic circular dichroism (MCD) and emission spectra of rat liver and rat kidney cadmium-, zinc- and copper-containing metallothioneins (MT) are reported. The absorption, CD and MCD data of native rat kidney Cd,Cu-MT protein closely resemble data recorded for the rat liver Cd,Zn-MT. This suggests that the major features in all three spectra of the native Cd,Cu-MT are dominated by cadmium-related bands. The CD spectrum of the Cd,Cu-MT recorded at pH 2.7 has the same band envelope that is observed for a Cd,Cu-MT formed in vitro by titration of Cd,Zn-MT with Cu(I), suggesting that the copper occupies the zinc sites in Cd,Cu-MT formed both in vivo and, at low molar ratios, in vitro. Remetallalion of the metallothionein from low pH in the presence of both copper and cadmium results in considerably less cadmium bound to the protein than was present in the native sample. It is suggested that this is due to the effect of the distribution of the copper amongst all available binding sites, thus inhibiting cluster formation by the cadmium. Emission spectra are reported for the first time for a cadmium- and copper-containing metallothionein. An emission band at 610 nm is shown to be a sensitive indicator of Cu(I) binding to metallothionein. Both the native Cd,Cu-MT and a Cd,Cu-MT formed in vitro exhibit an excitation spectrum with a band in the copper-thiolate charge-transfer region.
RESUMEN
The spin characteristics of the ferric heme groups in native beef liver catalase, and in the complexes formed by reaction with fluoride, cyanide, azide, thiocyanate, and cyanate ions have been studied using absorption spectroscopy over the temperature range of 4-285 K. The azide, isothiocyanate, and isocyanate complexes of catalase are considered to be high-spin ferric heme complexes at room temperature, but undergo a thermal spin change below 300 K. The temperature dependence of these absorption spectra, however, cannot be analyzed in terms of simple Boltzmann distributions between two S = 1/2 and S = 5/2 spin states. The data show that these spin changes occur over a very narrow temperature range, but do not result in the formation of completely, low-spin complexes. The data also suggest that the thermal spin changes that occur below the glassing temperature of the solvent are dependent upon the conformational changes which take place within the protein itself with a change in temperature, and which directly affect the environment of the heme group.
Asunto(s)
Catalasa , Hígado/enzimología , Animales , Azidas , Bovinos , Cianatos , Cianuros , Fluoruros , Espectrofotometría , Temperatura , TiocianatosRESUMEN
Absorption and magnetic circular dichroism (MCD) spectra are reported for chlorophyll (Chl) a and Chl b dissolved in nematic liquid crystal solvents. The spectra were measured with the dye molecules oriented uniaxially along the direction of. the magnetic field and measuring light beam. It is significant that under such conditions the MCD spectra recorded in the wavelength region of the Q and Soret bands of the chlorophyll are essentially unchanged with respect to rotation of the sample cell around this axis, even though there is almost complete orientation of the chlorophyll molecules by the liquid crystals. The MCD spectra of Chl a and b in the nematic liquid crystal solvents used in this study are surprisingly similar to the spectra obtained under isotropic conditions. These results illustrate an important technique with which to examine the optical spectra of dyes oriented in liquid crystal matrices in which the anisotropic effects can be reduced the negligible proportions by the application of a strong magnetic field parallel to the direction of the measuring light beam. The first deconvolution calculations are reported that describe the deconvolution of pairs of absorption and MCD spectra, in the Q and B band regions, for both Chl a and b. The spectral analysis to obtain quantitative estimates of transition energies was accomplished by carrying out detailed deconvolution calculations in which the both the absorption and MCD spectral envelopes were fitted with the same number of components; each pair of components had the same hand centres and bandwidth values. This procedure resulted in an assignment of each of the main transitions in the absorption spectra of both Chl a and b. Chl a is clearly monomeric, with Qy, Qx, By and Bx located at 671, 582, 439 and 431 nm, respectively. Analysis of the spectral data for Chl b located Qy, By and Bx, at 662, 476 and 464 nm, respectively.
RESUMEN
Few issues in health care have recently generated as much discussion as the two seemingly unrelated topics of out-of-hospital health care financing and compassionate care of patients at the end of life. These two topics meet where health care costs cross paths with the economic viability of hospice and palliative medicine. In this study, we evaluated 101 admissions to a large Medicare-certified hospice in the last quarter of 1995 to assess factors associated with timing of referral to hospice. Mean length of stay in hospice was 55 days; median was 23 days. The majority of patients had cancer diagnoses (74%). Contrary to our hypothesis, there was no statistically significant difference in mean patient lengths of stay between oncologist-referred and nononcologist-referred patients. However, when we compared patient lengths of stay lasting less than--versus longer than--30 days, more patients referred by nononcologists were in hospice longer than 30 days (chi 2 = 3.92, P < 0.05). With further evaluation, this difference was attributable to longer stays by patients covered by the Medicine hospice benefit, by those with noncancer diagnoses, and by those who were older. More of these patients were referred by nononcologists. The difference in referral patterns between oncologists and nononcologists disappeared when only cancer patients were considered. Consistent with initial hypotheses, caregivers of patients with shorter lengths of stay were significantly less satisfied with hospice care (t = -4.06, P < 0.001). These results suggest that health care benefits and other patient-specific issues influence timing of hospice referral rather than simply preferences by types of physicians. The impact on Medicare expenditures and hospice viability is discussed.
Asunto(s)
Accesibilidad a los Servicios de Salud , Cuidados Paliativos al Final de la Vida/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidado TerminalRESUMEN
The first fully energy-minimized structures for a series of structurally related metal complexes of the important mammalian metal binding protein metallothionein are described. The structures were calculated based on structural information obtained from existing spectroscopic and crystallographic data, and minimized using molecular mechanics (MM2) techniques. A two domain structure, with stoichiometries of M(II)3-(Scys)9 and M(II)4-(Scys)11 where M = zinc(II), cadmium(II), and mercury(II), was assembled and minimized. The resultant three-dimensional structure closely resembled that of rat liver Cd5Zn2-MT 1 obtained by analysis of x-ray diffraction data [A. H. Robbins, D.E. McRee, M. Williamson, S. A. Collett, N. H. Xuong, W. F. Furey, B. C. Wang and C. D. Stout, J. Mol. Biol. 221, 1269-1293 (1991)]. Minimized structures for Zn7-MT, Cd7-MT, and Hg7-MT are reported. Deep crevices that expose the metal-thiolate clusters are seen in each structure. However, for the mercury-containing protein, much of the mercury-thiolate structure is visible and it is proposed that this provides access for extensive interaction between solvent water molecules and the mercury(II), resulting in the observed distortion away from tetrahedral geometry for Hg7-MT. Volume calculations are reported for the protein metallated with 7 Zn(II), Cd(II), or Hg(II). A series of structural changes calculated for the step-wise isomorphous replacement of Zn(II) by Cd(II) and Hg(II) in the Zn4S11 alpha domain are shown.
Asunto(s)
Cadmio/química , Mercurio/química , Metalotioneína/química , Zinc/química , Secuencia de Aminoácidos , Animales , Sitios de Unión , Simulación por Computador , Cristalografía por Rayos X , Modelos Moleculares , Datos de Secuencia Molecular , Conformación Proteica , RatasRESUMEN
This study examined spatial memory as measured by radial arm maze (RAM) performance after exposure to two stress conditions and a normothermic-unrestrained control condition. Male Fischer 344 rats were trained on the win-shift RAM procedure for 7 days, by which time they achieved asymptotic performance. The next day, rats in the two stress groups were exposed to 15 min of restraint in either 37 degrees C water (normothermic-restraint) or in 20 degrees C water (cold-restraint). Rats were then allowed 40 min in a dry cage before being tested in the RAM. Performance was measured using the following dependent variables: number of correct out of the first eight choices, total number of choices, and time per choice. There were statistically significant effects of stress on all these variables; performance decrements were observed in both stress conditions relative to the normothermic-unrestrained condition. Normothermic-restrained rats displayed less impairment than cold-restrained rats on the stress day. Performance of normothermic-restrained rats returned to baseline levels the day after stress, whereas performance for the cold-restrained rats typically did not. This study demonstrates that: 1) restraint and cold stress impair performance on a memory task; and 2) impairment extent is related to stress severity. One of the mechanisms responsible for the observed behavioral deficits under cold stress may involve altered cholinergic function, because we previously demonstrated that hippocampal acetylcholine levels also decrease in relation to the severity of cold stress.
Asunto(s)
Memoria/fisiología , Percepción Espacial/fisiología , Estrés Psicológico/psicología , Animales , Temperatura Corporal/fisiología , Frío , Masculino , Aprendizaje por Laberinto/fisiología , Ratas , Ratas Endogámicas F344 , Restricción FísicaRESUMEN
Exposure to hypobaric hypoxia rapidly produces decrements in learning and memory. Tyrosine, a neurotransmitter precursor, has beneficial behavioral effects when administered to animals and humans exposed to various acute stressors. To determine whether tyrosine would protect rats from the adverse effects of hypobaric hypoxia on spatial reference and working memory, it was administered to 27 male Fischer 344 rats tested in the Morris water maze. Rats were tested starting at 2 and 6 h of an 8 h exposure to a simulated altitude of 5950 m (19,500 ft) or sea level. Tyrosine or placebo was administered 1/2 h prior to each testing session (400 mg/kg, IP). Altitude exposure significantly increased working memory escape latency; treatment with tyrosine reversed this decrement. There was no effect of altitude or tyrosine on reference memory. There were also no treatment-related differences in performance when animals were tested the next day at sea level. The beneficial effects of tyrosine on working memory performance may be due to a direct effect of tyrosine on memory, alleviation of a hypoxia-induced retardation of learning, or to other central or peripheral effects of this dietary catecholamine precursor.