Biomedical subjects

J I Rossato

Publications and source records attributed to J I Rossato.

5 recordsLinked to original sources

PubMed2006

On the participation of hippocampal p38 mitogen-activated protein kinase in extinction and reacquisition of inhibitory avoidance memory.

Inhibitory avoidance (IA) learning relies on the formation of an association between stepping down from a platform present in a certain context (conditioned stimulus; CS) with an aversive unconditioned stimulus (US; i.e. a footshock). A single CS-US pairing establishes a robust long-term memory expressed as an increase in step-down latency at testing. However, repeated retrieval of the avoidance response in the absence of the US induces extinction of IA memory. That is, recurring presentation of the CS alone results in a new learning indicating that the CS no longer predicts the US. Although the signaling pathways involved in the consolidation of IA and other fear-motivated memories have been profusely studied, little is known about the molecular requirements of fear memory extinction. Here we report that, as happens with its consolidation, extinction of IA long-term memory requires activity of the p38 subfamily of mitogen-activated protein kinases (MAPK) in the CA1 region of the dorsal hippocampus. Moreover, we found that inhibition of hippocampal p38MAPK blocked memory reacquisition after extinction without affecting either the increase in IA memory retention induced by a second training session or animal's locomotor/exploratory activity and anxiety state.

Animals↗

PubMed2006

The connection between the hippocampal and the striatal memory systems of the brain: a review of recent findings.

Two major memory systems have been recognized over the years (Squire, in Memory and Brain, 1987): the declarative memory system, which is under the control of the hippocampus and related temporal lobe structures, and the procedural or habit memory system, which is under the control of the striatum and its connections (Mishkin et al., in Neurobiology of Learning by G Lynch et al., 1984; Knowlton et al., Science 273:1399, 1996). Most if not all learning tasks studied in animals, however, involve either the performance or the suppression of movement. Animals acquire connections between environmental or discrete sensory cues (conditioned stimuli, CSs) and emotionally or otherwise significant stimuli (unconditioned stimuli, USs). As a result, they learn to perform or to inhibit the performance of certain motor responses to the CS which, when learned well, become what can only be called habits (Mishkin et al., 1984): to regularly walk or swim to a place or away from a place, or to inhibit one or several forms of movement. These responses can be viewed as conditioned responses (CRs) and may sometimes be very complex. This is of course also seen in humans: people learn how to play on a keyboard in response to a mental or written script and perform the piano or write a text; with practice, the performance improves and eventually reaches a high criterion and becomes a habit, performed almost if not completely without awareness. Commuting to school in a big city in the shortest possible time and eschewing the dangers is a complex learning that children acquire to the point of near-perfection. It is agreed that the rules that connect the perception of the CS and the expression of the CR change from their first association to those that take place when the task is mastered. Does this change of rules involve a switch from one memory system to another? Are different brain systems used the first time one plays a sonata or goes to school as compared with the 100th time? Here we will comment on: 1) reversal learning in the Morris water maze (MWM), in which the declarative or spatial component of a task is changed but the procedural component (to swim) persists and needs to be re-linked with a different set of spatial cues; and 2) a series of observations on an inhibitory avoidance task that indicate that the brain systems involved change with further learning.

Animals↗

PubMed2003

Voltage-dependent ebselen and diorganochalcogenides inhibition of 45Ca2+ influx into brain synaptosomes.

By mediating the Ca(2+) influx, Ca(2+) channels play a central role in neurotransmission. Chemical agents that potentially interfere with Ca(2+) homeostasis are potential toxic agents. In the present investigation, changes in Ca(2+) influx into synaptosomes by organic forms of selenium and tellurium were examined under nondepolarizing and depolarizing conditions induced by high KCl concentration (135 mM) or by 4-aminopyridine (4-AP). Under nondepolarizing conditions, ebselen (400 micro M) increased Ca(2+) influx; diphenyl ditelluride (40-400 micro M) decreased Ca(2+) in all concentrations tested; and diphenyl diselenide decreased Ca(2+) influx at 40 and 100 micro M, but had no effect at 400 micro M. In the presence of KCl as depolarizing agent, ebselen and diphenyl ditelluride decreased Ca(2+) influx in a linear fashion. In contrast, diphenyl diselenide did not modify Ca(2+) influx into isolated nerve terminals. In the presence of 4-AP (3 mM) as depolarizing agent, ebselen (400 micro M) caused a significant increase, whereas diphenyl diselenide and diphenyl ditelluride inhibited Ca(2+) influx into synaptosomes. The results can be explained by the fact that the mechanism through which 4-AP and high K(+) induced elevation of intracellular Ca(2+) is not exactly coincident. The mechanism by which diphenyl ditelluride and ebselen interact with Ca(2+) channel is unknown, but may be related to reactivity with critical sulfhydryl groups in the protein complex. The results of the present study indicate that the effects of organochalcogenides were rather complex depending on the condition and the depolarizing agent used.

4-Aminopyridine↗

PubMed2003

Src kinase activity is required for avoidance memory formation and recall.

Using 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-D]pyrimidine (PP2), a specific inhibitor of the Src family of tyrosine kinases, here we show a direct involvement of these enzymes in memory formation and recall. When infused into the CA1 region of the dorsal hippocampus, immediately or 30 min after training rats in a one-trial inhibitory avoidance task, PP2 but not its inactive analog 4-amino-7-phenylpyrazol[3,4-D]pyrimidine (PP3), blocked short- (STM) and long-term memory (LTM) formation, as tested 2 or 24 h post-training, respectively. PP2 had no effect on STM when given at 60 min post-training or on LTM when administered at 60, 120 or 180 min after the training session, but blocked memory recall when infused into CA1 15 min before a LTM expression test. Hence, activity of the Src family of tyrosine kinases is required in the CA1 region of the rat dorsal hippocampus for the normal formation and retrieval of one-trial inhibitory avoidance memory.

Animals↗

PubMed2002

Antioxidant properties of new chalcogenides against lipid peroxidation in rat brain.

Ebselen (2-phenyl- 1,2-benzisoselenazole-3 (2H)-one) is a seleno-organic compound with antioxidant properties, and anti-inflammatory actions. Recently, ebselen improved the outcome of acute ischemic stroke in humans. In the present study, the potential antioxidant capacity of organochalcogenide compounds diphenyl diselenide (PhSe)2, diphenyl ditelluride (PhTe)2, diphenyl disulfide (PhS)2, p-Cl-diphenyl diselenide (pCl-PhSe)2, bis-[S-4-isopropyl 2-phenyl oxazoline] diselenide (AA-Se)2, bis-[S-4-isopropyl 2-phenyl oxazoline] ditelluride (AA-Te)2 and bis-[S-4-isopropyl 2-phenyl oxazoline] disulfide (AA-S)2 was compared with that of ebselen (a classical antioxidant). Spontaneous and quinolinic acid (QA)- (2 mM) and sodium nitroprusside (SNP)- (5 microM)-induced thiobarbituric reactive species (TBARS) production by rat brain homogenates was determined colorimetrically. TBARS formation was reduced by ebselen, (PhSe)2, (PhTe)2, (AA-Se)2, (AA-S)2 and (pCl- PhSe)2 to basal rates. The concentrations of these compounds needed to inhibit TBARS formation by 50% (IC50) are 1.71 microM, 3.73 microM, 1.63 microM, 9.85 microM, >33.3 microM, 23.2 microM and 4.83 microM, respectively for QA. For TBARS production induced by SNP the IC50 was 2.02 microM, 12.5 microM, 2.80 microM, >33.3 microM, 24.5 microM and 7.55 microM, respectively. The compounds (AA-Te)2 and (PhS)2 have no antioxidant activity and pro-oxidant activity, respectively. These results suggest that (AA-Se)2 and (AA-S)2 can be considered as potential pharmaceutical antioxidant agents.

Animals↗