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L Manuel-Apolinar

Publications and source records attributed to L Manuel-Apolinar.

5 recordsLinked to original sources

5-HT1A receptor expression during memory formation.

RATIONALE: It has been reported that 5-HT(1A) receptors modulate learning and memory and diverse pharmacological and genetic evidence supports this notion. Nevertheless, there are few works about expression of these receptors during memory formation. OBJECTIVE: We aimed to determine 5-HT(1A) receptor expression in brain areas of untrained, passive, and autoshaping trained groups of rats. METHODS: Ex vivo receptor autoradiography using the ligand agonist [(3)H]8-hydroxy-2-[di-n-propylamino]tetralin] (8-OH-DPAT) was used. RESULTS: The trained group relative to untrained animals showed increases of 5-HT(1A) receptor expression in 14 brain areas, decrements in 7, and no changes in 12. Thus, in contrast to untrained rats, 5-HT(1A) receptor expression of autoshaping trained rats was augmented in the tubercule olfactory, septal nucleus, nucleus accumbens, caudate putamen, globus pallidus, striate, and parietal (1 and 2), temporal cortex (1 and 3), granular retrosplenial cortex (1), amygdala, and median and dorsal raphe nuclei. In contrast, in the latter group, receptors were decreased in the CA1 area, hypothalamus dorsal, frontal cortex (1 and 3), occipital cortex, cingulate cortex (1 and 2), and cuneiform nucleus. There were significant differences between passive vs trained groups, but not regarding untrained rats, in the lateral olfactory tract, dentate gyrus, CA3 area, ventromedial hypothalamic, lateral hypothalamus, preoptic medial, frontal cortex (2), granular retrosplenial cortex (2), entorhinal cortex (1 and 2), piriform cortex, and substantia nigra. CONCLUSIONS: These data suggest that upregulated, downregulated, and "silence" of 5-HT(1A) receptors in brain areas form part of neural circuits engaged in memory formation by demonstrating a high degree of specificity and memory mapping.

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

Modifications of 5-HT4 receptor expression in rat brain during memory consolidation.

Pharmacological evidence indicates a specific role of 5-HT(4) receptors on memory function. These receptors are members of G-protein-coupled 7-transmembrane domain receptor superfamily, are positively coupled to adenylyl cyclase, and are heterogeneously located in some structures important for memory, such as the hippocampus and cortical regions. To further clarify 5-HT(4) receptors' role in memory, the expression of these receptors in passive (P3) untrained and autoshaping (A3) trained (3 sessions) adult (3 months) and old (P9 or A9; 9 months) male rats was determined by autoradiography. Adult trained (A3) rats showed a better memory respect to old trained (A9). Using [(3)H] GR113808 as ligand (0.2 nM specific activity 81 Ci/mmol) for 5-HT(4) receptor expression, 29 brain areas were analyzed, 16 areas of A3 and 17 of A9 animals displayed significant changes. The medial mammillary nucleus of A3 group showed diminished 5-HT(4) receptor expression, and in other 15 brain areas of A3 or 10 of A9 animals, 5-HT(4) receptors were increased. Thus, for A3 rats, 5-HT(4) receptors were augmented in olfactory lobule, caudate putamen, fundus striatum, CA2, retrosplenial, frontal, temporal, occipital, and cingulate cortex. Also, 5-HT(4) receptors were increased in olfactory tubercule, hippocampal CA1, parietal, piriform, and cingulate cortex of A9. However, hippocampal CA2 and CA3 areas, and frontal, parietal, and temporal cortex of A9 rats, expressed less 5-HT(4) receptors. These findings suggest that serotonergic activity, via 5-HT(4) receptors in hippocampal, striatum, and cortical areas, mediates memory function and provides further evidence for a complex and regionally specific regulation over 5-HT receptor expression during memory formation.

Age Factors↗

Expression of the 5-HT receptors in rat brain during memory consolidation.

Serotonin (5-hydroxytryptamine, 5-HT) system displays more than 14 receptors subtypes on brain areas involved in learning and memory processes, and pharmacological manipulation of specific receptors selectively affects memory formation. In order to begin the search of 5-HT receptors expression during memory formation, in this work, we aimed to determine, by autoradiography (using 3H 5-HT as ligand, 2 nM, specific activity 123 Ci/mmol), 5-HT receptors (5-HTR) expression in passive (untrained) and autoshaping trained (3 sessions) adult (3 months) and old (9 months) male rats. Thus, trained adult rats had better retention than old animals. Raphe nuclei of adult and old trained rats expressed less receptors on medial and dorsal, respectively. Hippocampal CA1 area and dentate gyrus of adult trained rats expressed less 5-HTR, while dentate gyrus of old increased them. Basomedial amygdaloid nucleus in old trained rats expressed more 5-HTR; while in the basolateral amygdaloid nucleus they were augmented in both groups. Training decreased or did not change 5-HTR in caudate-putamen of adult or old animals. The above profile of 5-HTR expression is consistent with previous reports, and suggests that memory formation and aging modulates 5-HTR expression in brain areas relevant to memory systems.

Age Factors↗

8-OH-DPAT facilitated memory consolidation and increased hippocampal and cortical cAMP production.

Animals were submitted to an associative learning task named Pavlovian/instrumental autoshaping (P/I-A) and treated with selective 5-HT1A and 5-HT7 receptor agonists and antagonists. Next, they were sacrificed, their brains removed, dissected and changes on cortical and hippocampal cyclic adenosine monophosphate (cAMP) production were determined. Results revealed that, the 8-OH-DPAT treatment facilitated memory consolidation of autoshaping and that effect was blocked completely by WAY100635 and partially by DR4004. WAY100635 or DR4004 alone had no effect on autoshaping. The cAMP results were complex and yielded no clear relationship to the memory results. Thus, cortical and hippocampal increased on cAMP production was observed following administration of the 5-HT(1A/7) agonist 8-OH-DPAT. The memory effect was, completely or partially, reversed by the selective antagonists WAY100635 (5-HT1A) or DR4004 (5-HT7), respectively.

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

Frequency of macroprolactinemia due to autoantibodies against prolactin in pregnant women.

The frequency of macroprolactinemia related to the presence of anti-PRL autoantibodies in the serum of 209 healthy women at different stages of pregnancy was studied. Measurements were taken of serum PRL concentrations before and after chromatographic separation (gel filtration and affinity with proteins A and G) and extraction of free PRL with polyethylene glycol (PEG). Sera from 8 of the 209 women (3.8%) were found to have a significantly high proportion of precipitated PRL by PEG (macroprolactinemia); in these patients, gel filtration showed that a substantial amount of big big PRL (molecular mass >100 kDa) was present (19.0--78.2% vs. 3.8-4.9%, P = 0.009 in normal pregnant women with a normal proportion of precipitated PRL by PEG). The presence of macroprolactinemia was attributable to anti-PRL autoantibodies in 5 of the 8 women. Comparison of serum levels of direct and free PRL between women with macroprolactinemia related to anti-PRL autoantibodies and women without macroprolactinemia showed significant differences (direct PRL: 270.2 +/- 86.9 vs. 203.4 +/- 69.0 microg/L, P = 0.04; and free PRL: 107.0 +/- 75.9 vs. 173.3 +/- 67.6 microg/L, P = 0.002). On the other hand, there was no difference between women with macroprolactinemia not related to anti-PRL autoantibodies and women with macroprolactinemia caused by anti-PRL autoantibodies, nor was there a difference between women with macroprolactinemia not related to anti-PRL autoantibodies and women without macroprolactinemia. There was a positive correlation between titers of the anti-PRL autoantibody and serum PRL levels (r = 0.82, P = 0.09). The presence of the anti-PRL autoantibody had no relation to the patient's age, stage of gestation, or number of previous pregnancies. We concluded that the frequency of macroprolactinemia was 3.8% among healthy, pregnant women, which was caused by a anti-PRL autoantibodies in 62.5% of the cases. The autoantibodies were found in the bloodstream, forming a PRL-IgG complex, in accordance with the following observations: 1) immunoreactive PRL on gel filtration was eluted in the fractions corresponding to the molecular mass of IgG (150 kDa); 2) a significantly high proportion of immunoreactive PRL was retained on an affinity gel for IgG (proteins A and G); and 3) a significantly high proportion of serum PRL bound to IgG was precipitated by protein A. There was a positive correlation between titers of anti-PRL autoantibodies and serum PRL levels. Serum levels of total PRL were higher, and serum levels of free PRL were lower, in pregnant women with anti-PRL autoantibodies than in pregnant women without macroprolactinemia.

Adult↗