222 research outputs found
Amygdaloid Kindling and the GABA System
The effect of increased brain GABA levels on fully kindled amygdala seizures was investigated in Long-Evans rats. The newly synthesized GABA-transaminase inhibitor, -Î-acetylenic GABA (GAG) administered on four consecutive days (100 mg/kg, followed by 50 mg/kg, i.p.) was found to either significantly reduce, or eliminate entirely, the behavioral seizures normally produced by amygdala stimulation. The effect is seen after the first injection of GAG although its magnitude was greater on subsequent days. Behavioral seizures reappeared 2 to 3 days after termination of GAG treatment. The duration of electrographic seizures (self-sustained amygdala after-discharge) was either unchanged or greater on the first day of GAG treatment, but was briefer on subsequent days. The duration of afterdischarges returned to normal levels 1 to 2 days earlier than the behavioral seizures after the termination of GAG. Picrotoxin (1.5-2 mg/kg, i.p.) did not antagonize either electrographic or behavioral effects of inhibition produced with GAG. Electrical stimulation of amygdala delivered during the initial sedation stage induced by picrotoxin resulted in further regression of kindled seizures in the majority of animals. Although in doses employed, GAG alleviates amygdaloid-kindled seizures its use requires caution in view of its ability to reduce arousal level. RĂSUMĂ L'effet de l'ĂlĂvation des taux cĂrĂbraux de GABA sur les crises amygdaliennes par effet d'embrasement complet a ĂtĂĂtudiĂ chez des rats Long-Evans. l'injection pendant 4 jours consĂcutifs de 100 mg/kg suivis de 50 mg/kg i.p. d'un inhibiteur de la GABA. Transaminase nouvellement synthĂtisĂ (Î-acetylenic GABA ou GAG) a significativement rĂduit ou mĂme supprimĂ les crises normalement provoquĂes par la stimulation amygdalienne. l'effet est observĂ aprĂs la premiere injection de GAG, mais son importance s'accroit les jours suivants. Les crises rĂapparaissent 2 ou 3 jours aprĂs la fin du traitement au GAG. Du point de vue Ălectrographique, la durĂe de la postdĂcharge amygdalienne autoentretenue est inchingĂe ou accrue le premier jour du traitement, mais elle diminue les jours suivants pour retourner Ă la normale un ou deux jours avant que les crises ne rĂapparaissent aprĂs la fin de ('administration du GAG. l'injection de picrotoxine (1.5-2 mg/kg i.p.) ne s'oppose pas aux effets inhibiteurs du GAG sur les crises ou leur accompagnement EEG. La stimulation Ălectrique de l'amygdala pendant l'Ătape sĂdative initiate induite par la picrotoxine provoque une rĂgression supplĂmentaire des crises d'embrasement chez la majoritĂ des animaux. Bien que, aux doses utilisĂes, le GAG attĂnue les crises amyg-daliennes d'embrasement, son utilisation nĂcessite des prĂcautions compte tenu de sa tendance Ă rĂduire le niveau d'Ăveil. RESUMEN En ratas Long-Evans se ha investigado el efecto del aumento de los niveles cerebrales de GABA, sobre los ataques originados en la amĂgdala totalmente condicionada, (Kindling). El recientemente sintetizado in-hibidor de la GABA transaminasa, Î-acetilĂnico GABA (GAG), redujo significativamente o eliminĂ totalmente las crisis de comportamiento que habitualmente se producen con la estimulaciĂn de la amĂgdala. El efecto se observa despuĂs de la primera in-yecciĂn de GAG pero su magnitud aumentĂ en dias subsiguientes. Las crisis de comportamiento reaparecieron a los 2â3 dĂas de la interrupciĂn del tratamiento con GAG. La duraciĂn de los ataques electrogrĂficos (perservaciĂn de la post-descarga de la amigdala) no se modificĂ, o incluso aumentĂ, en el primer dia de la administraciĂn de GAG pero se redujo en los dias siguientes. La duraciĂn de las post-descargas volviĂ a sus niveles normales 1 o 2 dias antes que la reapariciĂn de las crisis de comportamiento una vez terminado el tratamiento con GAG. La picrotoxina (1.5-2 mg/kg, i.p.) no antagonizĂ los efectos inhibitorios producidos por el GAG sobre el electroencefalograma o las crisis de comportamiento. La estimulaciĂn elĂctrica sobre la amĂgdala, aplicada durante la fase de sedaciĂn inicial inducida por la picrotoxina, condujo a una regresiĂn aĂn mĂs intensa de las crisis condicionadas, en la mayorĂa de los animales. A pesar de que, con las dosis utilizadas, el GAG alivia las crisis de la amĂgdala previamente condicionada, se requiere gran precauciĂn en su utilizaciĂn en vista de su propiedad de reducir el nivel del despertar. ZUSAMMENFASSUNG Die Wirkung erhĂhter GABA-Spiegel des Gehirns auf AmygdalonkrĂmpfe nach Kindling wurden bei Long-Evans-Ratten untersucht. Der neuerdings synthetisierte GABA-TYansaminasen-Inhibitor, Gamma-Acetylen-GABA (GAG) wurde an 4 aufeinander-folgenden Tagen in einer Dosis von 100 mg/kg und anschlieliend 50 mg/kg i.p. verabfolgt. Er reduzierte entweder signifikant oder eliminierte vĂllig die anfalls-weisen VerhaltensĂnderungen, die normalerweise durch Stimulation des Amygdalon produziert wurden. Die Wirkung ist nach der Erstinjektion des GAG zu beobachten, obgleich ihr AusmaĂ an folgenden Tagen grĂĂer war. Die VerhaltensanfĂlle kamen 2 bis 3 Tagen nach Beendigung der GAG-Behandlung wieder. Die Dauer der elektrographischen AnfĂlle (sich selbst un-terhaltende Amydalonnachentladungen) blieben entweder gleich oder sie wurden grĂĂer am 1. Tag der GAG-Behandlung, wurden aber kĂrzer an folgenden Tagen. Die Dauer der Nachentladungen nor-malisierte sich 1 bis 2 Tage frĂher als die VerhaltensanfĂlle nach Beendigung des GAG verschwanden. Picrotoxin (1.5 bis 2 mg/kg i.p.) wirken nicht als Antagonist gegenĂber der durch GAG produzierten Hemmung der elektrographischen-oder Verhalten-seffekte. Die elektrische Stimulierung des Amygdalon wĂhrend der initialen Sedierung nach Picrotoxin ver-ursachte bei der Mehrzahl der Tiere einen weiteren RĂckgang der durch Kindling entstandenen AnfĂlle. Obgleich das GAG in den verwandten Dosen, die durch Kindling des Amygdalon erzeugten KrĂmpfe leichter ablaufen lUĂt, erfordert seine Anwendung Vorsicht hinsichtlich seiner FĂhigkeit, das Erreg-barkeitsniveau zu senken.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66112/1/j.1528-1157.1980.tb04058.x.pd
Determining the neurotransmitter concentration profile at active synapses
Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission
Homeostatic regulation of the endoneurial microenvironment during development, aging and in response to trauma, disease and toxic insult
The endoneurial microenvironment, delimited by the endothelium of endoneurial vessels and a multi-layered ensheathing perineurium, is a specialized milieu intĂŠrieur within which axons, associated Schwann cells and other resident cells of peripheral nerves function. The endothelium and perineurium restricts as well as regulates exchange of material between the endoneurial microenvironment and the surrounding extracellular space and thus is more appropriately described as a bloodânerve interface (BNI) rather than a bloodânerve barrier (BNB). Input to and output from the endoneurial microenvironment occurs via bloodânerve exchange and convective endoneurial fluid flow driven by a proximo-distal hydrostatic pressure gradient. The independent regulation of the endothelial and perineurial components of the BNI during development, aging and in response to trauma is consistent with homeostatic regulation of the endoneurial microenvironment. Pathophysiological alterations of the endoneurium in experimental allergic neuritis (EAN), and diabetic and lead neuropathy are considered to be perturbations of endoneurial homeostasis. The interactions of Schwann cells, axons, macrophages, and mast cells via cellâcell and cellâmatrix signaling regulate the permeability of this interface. A greater knowledge of the dynamic nature of tight junctions and the factors that induce and/or modulate these key elements of the BNI will increase our understanding of peripheral nerve disorders as well as stimulate the development of therapeutic strategies to treat these disorders
The effects of a protein enriched diet with lean red meat combined with a multi-modal exercise program on muscle and cognitive health and function in older adults: study protocol for a randomised controlled trial
Organic pollutants in sea-surface microlayer and aerosol in thecoastal environment of Leghornâ(Tyrrhenian Sea)
The levels of dissolved and particle-associated n-alkanes, alkylbenzenes, phthalates, PAHs, anionic surfactants and
surfactant fluorescent organic matter ŽSFOM. were measured in sea-surface microlayer ŽSML. and sub-surface water ŽSSL.
samples collected in the Leghorn marine environment in September and October 1999.
Nine stations, located in the Leghorn harbour and at increasing distances from the Port, were sampled three times on the
same day. At all the stations, SML concentrations of the selected organic compounds were significantly higher than SSL
values and the enrichment factors ŽEFsSML concentrationrSSL concentration. were greater in the particulate phase than
in the dissolved phase.
SML concentrations varied greatly among the sampling sites, the highest levels Žn-alkanes 3674 mgrl, phthalates 177
mgrl, total PAHs 226 mgrl. being found in the particulate phase in the Leghorn harbour.
To improve the knowledge on pollutant exchanges between sea-surface waters and atmosphere, the validity of spray drop
adsorption model ŽSDAM. was verified for SFOM, surface-active agents, such as phthalates, and compounds which can
interact with SFOM, such as n-alkanes and PAHs. q2001 Elsevier Science B.V. All rights reserved
Sarcopenia; Aging-related loss of muscle mass and function
Sarcopenia is a loss of muscle mass and function in the elderly that reduces mobility, diminishes quality of life, and can lead to fall-related injuries, which require costly hospitalization and extended rehabilitation. This review focuses on the aging-related structural changes and mechanisms at cellular and subcellular levels underlying changes in the individual motor unit: specifically, the perikaryon of -motoneuron, its neuromuscular junction(s), and the muscle fibers that it innervates. Loss of muscle mass with aging, which is largely due to the progressive loss of motoneurons, is associated with reduced muscle fiber number and size. Muscle function progressively declines because motoneuron loss is not adequately compensated by reinnervation of muscle fibers by the remaining motoneurons. At the intracellular level, key factors are qualitative changes in posttranslational modifications of muscle proteins and the loss of coordinated control between contractile, mitochondrial, and sarcoplasmic reticulum protein expression. Quantitative and qualitative changes in skeletal muscle during the process of aging also have been implicated in the pathogenesis of acquired and hereditary neuromuscular disorders. In experimental models, specific intervention strategies have shown encouraging results on limiting deterioration of motor unit structure and function under conditions of impaired innervation. Translated to the clinic, if these or similar interventions, by saving muscle and improving mobility, could help alleviate sarcopenia in the elderly, there would be both great humanitarian benefits and large cost savings for health care systems
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