Interfering with Fos expression in rat perirhinal cortex impairs recognition memory.

Previous work has shown that immunohistochemical imaging of Fos protein is a reliable marker for changes in activity related to recognition memory in the perirhinal (PRH) cortex of the medial temporal lobe; however, whether PRH Fos expression is necessary for recognition memory had not been established. To investigate this potential requirement, antisense Fos oligodeoxynucleotide (ODN) was infused locally into PRH cortex to interfere with Fos production. As in previous studies, differential Fos expression produced by viewing novel or familiar visual stimuli was measured by immunohistochemistry: antisense Fos ODN infusion into PRH cortex disrupted the normal pattern of differential Fos expression in PRH cortex. The effect of antisense Fos ODN infusion into PRH cortex was therefore sought on recognition memory. Infusion before or immediately after acquisition impaired recognition memory for objects when the memory delay was 3 or 24 h, but not when the delay was 20 min, or when the ODN was infused before retrieval after a 24-h delay. The findings indicate a role for Fos in consolidation processes underlying long-term recognition memory for objects and establish that interfering with its expression impairs recognition memory. Antisense Fos ODN infusion also impaired object-in-place recognition memory. The results demonstrate that Fos is necessary for neuronal mechanisms in PRH cortex essential to recognition memory.

Interfering with perirhinal brain-derived neurotrophic factor expression impairs recognition memory in rats.

The role of brain-derived neurotrophic factor (BDNF) in recognition memory was investigated by locally infusing oligodeoxynucleotides (ODNs) into perirhinal cortex, a region of the temporal lobe essential for familiarity discrimination. Antisense but not sense BDNF ODN impaired consolidation of long-term (24 h) but not shorter-term (20 min) recognition memory.

Proteins involved in platelet signaling are differentially regulated in acute coronary syndrome: a proteomic study.

BACKGROUND: Platelets play a fundamental role in pathological events underlying acute coronary syndrome (ACS). Because platelets do not have a nucleus, proteomics constitutes an optimal approach to follow platelet molecular events associated with the onset of the acute episode. METHODOLOGY/PRINCIPAL FINDINGS: We performed the first high-resolution two-dimensional gel electrophoresis-based proteome analysis of circulating platelets from patients with non-ST segment elevation ACS (NSTE-ACS). Proteins were identified by mass spectrometry and validations were by western blotting. Forty protein features (corresponding to 22 unique genes) were found to be differentially regulated between NSTE-ACS patients and matched controls with chronic ischemic cardiopathy. The number of differences decreased at day 5 (28) and 6 months after the acute event (5). Interestingly, a systems biology approach demonstrated that 16 of the 22 differentially regulated proteins identified are interconnected as part of a common network related to cell assembly and organization and cell morphology, processes very related to platelet activation. Indeed, 14 of those proteins are either signaling or cytoskeletal, and nine of them are known to participate in platelet activation by αIIbß3 and/or GPVI receptors. Several of the proteins identified participate in platelet activation through post-translational modifications, as shown here for ILK, Src and Talin. Interestingly, the platelet-secreted glycoprotein SPARC was down-regulated in NSTE-ACS patients compared to stable controls, which is consistent with a secretion process from activated platelets. CONCLUSIONS/SIGNIFICANCE: The present study provides novel information on platelet proteome changes associated with platelet activation in NSTE-ACS, highlighting the presence of proteins involved in platelet signaling. This investigation paves the way for future studies in the search for novel platelet-related biomarkers and drug targets in ACS.

The targets of acetone cyanohydrin neurotoxicity in the rat are not the ones expected in an animal model of konzo.

Konzo is a neurotoxic motor disease caused by excess consumption of insufficiently processed cassava. Cassava contains the cyanogenic glucoside linamarin, but konzo does not present the known pathological effects of cyanide. We hypothesized that the aglycone of linamarin, acetone cyanohydrin, may be the cause of konzo. This nitrile rapidly decomposes into cyanide and acetone, but the particular exposure and nutrition conditions involved in the emergence of konzo may favor its stabilization and subsequent acute neurotoxicity. A number of preliminary observations were used to design an experiment to test this hypothesis. In the experiment, young female Long-Evans rats were given 10mM acetone cyanohydrin in drinking water for 2 weeks, and then 20mM for 6 weeks. Nutrition deficits associated with konzo were modeled by providing tapioca (cassava starch) as food for the last 3 of these weeks. After this period, rats were fasted for 24h in order to increase endogenous acetone synthesis, and then exposed to 0 (control group) or 50 micromol/kg-h of acetone cyanohydrin for 24h (treated group) through subcutaneous osmotic minipump infusion (n=6/group). Motor activity and gait were evaluated before exposure (pre-test), and 1 and 6 days after exposure. Brains (n=4) were stained for neuronal degeneration by fluoro-jade B. Rats exposed to 50 micromol/kg-h of acetone cyanohydrin showed acute signs of toxicity, but no persistent motor deficits. Two animals showed fluoro-jade staining in discrete thalamic nuclei, including the paraventricular and the ventral reuniens nuclei; one also exhibited labeling of the dorsal endopiriform nucleus. Similar effects were not elicited by equimolar KCN exposure. Therefore, acetone cyanohydrin may cause selective neuronal degeneration in the rat, but the affected areas are not those expected in an animal model of konzo.

L-type voltage-dependent calcium channel antagonists impair perirhinal long-term recognition memory and plasticity processes.

The perirhinal cortex of the temporal lobe is essential for the familiarity discrimination component of recognition memory. In view of the importance of changes in calcium ion concentration for synaptic plasticity, the present study examined the effects of L-type voltage-dependent calcium channel (VDCC) antagonism on rat perirhinal-based familiarity discrimination processes and plasticity including long-term depression (LTD), long-term potentiation (LTP), and depotentiation. Single doses of three different types of L-type VDCC antagonists, verapamil, diltiazem, and nifedipine, administered systemically, or verapamil administered locally into the perirhinal cortex, impaired acquisition of long-term (24 h) but not shorter-term (20 min) recognition memory. L-type VDCC antagonism also disrupted memory retrieval after 24 h but not 20 min. Differential neuronal activation produced by viewing novel or familiar visual stimuli was measured by Fos expression. L-type VDCC antagonism by verapamil in perirhinal cortex during memory acquisition disrupted the normal pattern of differential Fos expression, so paralleling the antagonist-induced memory impairment. In slices of perirhinal cortex maintained in vitro, verapamil was without effect on baseline excitability or LTP but blocked LTD and depotentiation. The consistency of effects across the behavioral and cellular levels of analysis provides strong evidence for the involvement of perirhinal L-type VDCCs in long-term recognition memory processes.

Extruding auditory hair cells in rats exposed to subchronic 3,3'-iminodipropionitrile.

Hair cell loss by extrusion of nearly intact cells towards the endolimphatic cavity has been reported in the vestibular epithelia of rats subchronically exposed to 3,3'-iminodipropionitrile (IDPN). To investigate whether hair cell extrusion also occurs in the auditory system, adult male Long-Evans rats were exposed to IDPN through drinking water (0.2-0.4% for 4-14 weeks), and their organ of Corti were examined by light and scanning electron microscopy. IDPN exposure caused loss and protrusion of the outer hair cells. The surface appearance of the protruding outer hair cells was similar to that of extruding vestibular hair cells. However, the former showed cell shrinkage and irregularly shaped nucleus, by contrast to the almost normal ultrastructure shown by the latter. The results indicate that outer hair cells can suffer extrusion, but the final outcome of this process (complete extrusion versus apoptosis) remains to be determined.

Distal effects in a model of proximal axonopathy: 3,3'-iminodipropionitrile causes specific loss of neurofilaments in rat vestibular afferent endings.

3,3'-Iminodipropionitrile (IDPN) is a neurotoxic compound that causes both a proximal neurofilamentous axonopathy and loss of the vestibular sensory hair cells. We used immunocytochemistry to examine changes in the expression of heavy, medium and light neurofilament (NF-H, NF-M, NF-L) proteins in the afferent terminals of vestibular sensory epithelia after IDPN exposure in rats. Acute, repeated and subchronic IDPN exposure induced a marked loss of NFs in the nerve terminals. The effect of subchronic IDPN was specific, as demonstrated by comparison with the synaptic membrane protein SNAP-25. In addition, Western blot analysis indicated specific loss of NFs in the vestibular receptors. Ultrastructural analysis revealed that afferent endings in the vestibular receptors were significantly preserved in animals exposed to subchronic IDPN, but that these endings showed NF segregation from microtubules followed by NF loss. These effects were closely paralleled by ultrastructural changes in the nerve terminals, particularly in the afferent contacts with the hair cells, and preceded hair cell loss. Thus, distal NF loss and nerve terminal pathology occur in the IDPN model of proximal neurofilamentous axonopathy. Similar distal pathology could also occur in human diseases characterized by proximal axonal swellings, particularly in amyotrophic lateral sclerosis.

Estudio de la mortalidad en recién nacidos con peso superior a 2 500 gramos / Study of mortality in newborn weighing more than 2 500 g

Se estudian los recièn nacidos vivos con peso mayor de 2 500 gramos que fallecieron durante el decennio de enero de 1978 a diciembre de 1987 en el Hospital Docente Ginecoobstétrico de Guanabacoa. Dicho estudio comprendió 114 fallecidos de un total de 28 669 nacidos vivos de ese peso, para una tasa de mortalidad (de o,4) por 1 000 nacidos vivos y las principales causas de muerte fueron: asfixia, malformaciones y bronconeumonía congénita. En el análisis se encontró alta mortalidad en el recién nacido mayor de 4 000 g y en el hijo de madre adolescente. El alto porcentaje de recién nacidos asfìcticos por cesárea nos señalan su indicación tardía. Por último, no se encontró relación entre enfermedad materna propia o asociada con el embarazo y mortalidad neonatal en los recién nacidos de nuestro estudio