5-HT7 receptor activation: procognitive and antiamnesic effects.

RATIONALE: The serotonin (5-hydroxytryptamine (5-HT)) 5-HT7 receptor is localized in brain areas mediating memory; however, the role of this receptor on memory remains little explored. OBJECTIVE: First, demonstrating the associative nature of Pavlovian/instrumental autoshaping (P/I-A) task, rats were exposed (three sessions) to CS-US (Pavlovian autoshaping), truly random control, free operant, and presentations of US or CS, and they were compared with rats trained-tested for one session to the P/I-A procedure. Also, effects of the 5-HT7 receptor agonist LP-211 administered intraperitoneally after training was determined on short- (1.5 h) and long-term memory 24 and 48 h) and on scopolamine-induced memory impairment and cAMP production. METHODS: Autoshaping and its behavioral controls were studied. Other animals were subjected to an autoshaping training session and immediately afterwards were given (intraperitoneal) vehicle or LP-211 (0.1-10 mg/kg) and/or scopolamine (0.2 mg/kg) and tested for short-term memory (STM) and long-term memory (LTM); their brains were extracted for the cAMP ELISA immunoassay. RESULTS: P/I-A group produced the higher %CR. LP-211 did not affect STM; nonetheless, at 0.5 and 1.0 mg/kg, it improved LTM. The 5-HT7 receptor antagonist SB-269970 (SB; 10.0 mg/kg) alone had no effect; nevertheless, the LP-211 (1.0 mg/kg) LTM facilitation was reversed by SB. The scopolamine (0.2 mg/kg) induced-decrement in CR was accompanied by significant increased cAMP production. The scopolamine-induced decrement in CR and increments in cAMP were significantly attenuated by LP-211. CONCLUSIONS: Autoshaping is a reliable associative learning task whose consolidation is facilitated by the 5-HT7 receptor agonist LP-211.

Differential developmental programming by early protein restriction of rat skeletal muscle according to its fibre-type composition.

AIMS: Differences in fibre-type composition of skeletal muscle have been associated with obesity and insulin resistance. As a poor nutrient environment early in life is a predisposing factor for the development of obesity and related metabolic diseases at adulthood, this study aimed at determining the long-term consequences of maternal undernutrition on the structural and metabolic properties of two skeletal muscles characterized by their different fibre-type composition and metabolic properties. METHODS: The fibre-type composition and enzymatic activities of hexokinase (HK), beta-hydroxyacyl-CoA dehydrogenase (ß-HAD) and citrate synthase (CS) were measured in soleus and extensor digitorum longus (EDL) muscles from adult rats born to dams fed a control (17% protein) or a low-protein [8% protein (PR)] diet throughout pregnancy and lactation. In addition, the expression levels of several genes regulating glycolysis, fatty acid oxidation and mitochondrial biogenesis were determined by real-time PCR. RESULTS: Protein rats exhibited enhanced density of type II fibres along with decreased rate of fatty acid oxidation and glycolysis in soleus but not EDL. Malnourished rats exhibited also a different gene expression profile in soleus and EDL. Altogether, these alterations correspond to a state of energy deficiency and are present in animals which do not show yet any sign of obesity or glucose intolerance. CONCLUSION: We conclude that maternal protein restriction alters in the long term the structural and enzymatic properties of offspring skeletal muscle in a fibre-type-dependent manner. These alterations might have a causative role in the development of obesity and related metabolic disorders later in life.

Time-course of 5-HT(6) receptor mRNA expression during memory consolidation and amnesia.

Growing evidence indicates that antagonists of the 5-hydroxytryptamine (serotonin) receptor(6) (5-HT(6)) improve memory and reverse amnesia although the mechanisms involved are poorly understood. Hence, in this paper RT-PCR was used to evaluate changes in mRNA expression of 5-HT(6) receptor in trained and untrained rats treated with the 5-HT(6) receptor antagonist SB-399885 and amnesic drugs scopolamine or dizocilpine. Changes in mRNA expression of 5-HT(6) receptor were investigated at different times in prefrontal cortex, hippocampus and striatum. Data indicated that memory in the Pavlovian/instrumental autoshaping task was a progressive process associated to reduced mRNA expression of 5-HT(6) receptor in the three structures examined. SB-399885 improved long-term memory at 48h, while the muscarinic receptor antagonist scopolamine or the non-competitive NMDA receptor antagonist dizocilpine impaired it at 24h. Autoshaping training and treatment with SB-399885 increased 5-HT(6) receptor mRNA expression in (maximum increase) prefrontal cortex and striatum, 24 or 48h. The scopolamine-induced amnesia suppressed 5-HT(6) receptor mRNA expression while the dizocilpine-induced amnesia did not modify 5-HT(6) receptor mRNA expression. SB-399885 and scopolamine or dizocilpine were able to reestablish memory and 5-HT(6) receptor mRNA expression. These data confirmed previous memory evidence and of more interest is the observation that training, SB-399885 and amnesic drugs modulated 5-HT(6) receptor mRNA expression in prefrontal cortex, hippocampus and striatum. Further investigation in different memory tasks, times and amnesia models together with more complex control groups might provide further clues.

Ex vivo study of 5-HT(1A) and 5-HT(7) receptor agonists and antagonists on cAMP accumulation during memory formation and amnesia.

The cyclic adenosine monophosphate (cAMP) is a second messenger and a central component of intracellular signaling pathways that regulate a wide range of biological functions, including memory. Hence, in this work, firstly the time-course of memory formation was determined in an autoshaping learning task, which had allowed the identification of testing times for increases or decreases in performance. Next, untrained, trained and overtrained groups were compared in cAMP production. Moreover, selective stimulation and antagonism of 5-HT(1A) and 5-HT(7) receptors during memory formation and cAMP production were determined. Finally, since there is scarce information about how pharmacological models of amnesia affect cAMP production, the cholinergic or glutamatergic antagonists, scopolamine and dizocilpine, were tested. The major findings of this work showed that when the time-course was determined inasmuch as training and testing sessions occurred, memory performance was graduate and progressive. Notably, for the fourth to seventh (i.e., 48-120 h following autoshaping training session) testing session performance was significantly higher from the previous ones. When animals received 5-HT(1A) and 5-HT(7) receptor agonists and antagonists or amnesic drugs significant increases or decrements in memory performance were observed at 24 and 48 h. Moreover, when ex vivo cAMP production from trained and overtrained groups were compared to untrained ones, significant differences were observed among groups and brain areas. Trained animals treated with 8-OHDPAT, AS19, 8-OHDPAT plus AS19, WAY100635, SB-269970, scopolamine or dizocilpine were compared to similar untrained groups, and eightfold-reduced cAMP production was evident, showing the importance of cAMP production in the signaling case in mammalian memory formation.

The effects of the 5-HT(6) receptor agonist EMD and the 5-HT(7) receptor agonist AS19 on memory formation.

Growing evidence indicates that 5-hydrohytryptamine (5-HT) receptors mediate learning and memory. Particularly interesting are 5-HT(6) and 5-HT(7) receptors, which are localized in brain areas involved in memory formation. Interestingly, recently selective 5-HT(6) and 5-HT(7) receptor agonists and antagonists have become available. Previous evidence indicates that 5-HT(6) or 5-HT(7) receptors antagonists had no effects, improved memory formation and/or reversed amnesia. Herein, the effects of EMD (a 5-HT(6) receptor agonist) and AS19 (a 5-HT(7) receptor agonist) in the associative learning task of autoshaping were studied. Post-training systemic administration of EMD (1-10 mg/kg) or AS19 (1-10 mg/kg) were tested in short-term memory (STM) and long-term memory (LTM). Results showed that only EMD 5.0mg/kg impaired both STM and LTM. AS19 at 1-10 mg/kg significantly impaired STM but not LTM. In those groups used to test only LTM, EMD impaired it; while AS19 improved LTM. Moreover, in the interaction experiments, the STM EMD-impairment effect was partially reversed by the selective 5-HT(6) receptor antagonist SB-399885 (10 mg/kg). The STM AS19-impairment effect (5.0 mg/kg) was not altered by the selective 5-HT(1A) antagonist WAY 100635 (0.3 mg/kg) but reversed by the selective 5-HT(7) receptor antagonist SB-269970 (10.0 mg/kg). The AS19-SB-269970 combination impaired LTM. Taken together these data suggest that the stimulation of 5-HT(6) impaired both STM and LTM. 5-HT(7) receptors stimulation impaired STM but improved LTM. And these results are discussed in the context of their possible neural bases.

Memory formation, amnesia, improved memory and reversed amnesia: 5-HT role.

Traditionally, the search for memory circuits has been focused on examinations of amnesic and AD patients, cerebral lesions and neuroimaging. A complementary alternative has become the use of autoradiography with radioligands, aiming to identify neurobiological markers associated with memory formation, amnesia states and (more recently) recovery from memory deficits. Indeed, ex vivo autoradiographic studies offer the advantage of detecting functionally active receptors altered by pharmacological tools during memory formation, amnesia states and memory recovery. Moreover, serotonin (5-hydroxytryptamine, 5-HT) systems have become a pharmacological and genetic target in the treatment of memory disorders. Herein evidence from studies involving expression of 5-HT(1A), 5-HT(2A), 5-HT(4), and 5-HT(6) receptors in memory formation, amnesia conditions (e.g., pharmacological models or aging) and recovery of memory is reviewed. Thus, specific 5-HT receptors were expressed in trained animals relative to untrained in brain areas such as cortex, hippocampus and amygdala. However, relative to the control group, rats showing amnesia or recovered memory, showed in the hippocampus, region where explicit memory is formed, a complex pattern of 5-HT receptor expression. An intermediate expression occurred in amygdala, septum and some cortical areas in charge of explicit memory storage. Even in brain areas thought to be in charge of procedural memory such as basal ganglia, animals showing recovered memory displayed an intermediate expression, while amnesic groups, depending on the pharmacological amnesia model, showed up- or down-regulation. In conclusion, evidence indicates that autoradiography, by using specific radioligands, offers excellent opportunities to map dynamic changes in brain areas engaged in these cognitive processes. The 5-HT modulatory role strengthens or suppresses memory is critically depend on the timing of the memory formation.

A further whole arm 1;19 translocation with alpha-satellite DNA breakage.

A balanced whole arm translocation (1;19)(p10;q10) was found in a woman with normal phenotype ascertained through a fragile X survey. Chromosome painting with the specific libraries confirmed the cytogenetic diagnosis. Fluorescence in situ hybridization with a chromosome-1 alpha-satellite probe revealed that the breakpoint in chromosome 1 split the alpha-satellite sequences into two blocks. The review of constitutional whole arm translocations revealed a greater participation of some chromosomes with recurrence of translocations t(1;19)(1p19q;1q19p), t(18;20)(18p20q;18q20p) and t(X;17)(Xp17q;Xq17p). The alpha-satellite breakage documented in some derivatives of the recurrent translocations may be related to highly homologous subsets in the involved chromosome pairs, which belong to alpha-satellite subfamilies 1, 2 and 3 respectively. Probably this leads to abnormal chromosome pairing and thus to whole arm translocations.

[AEC syndrome: ankyloblepharon, ectodermal defect, cleft lip and palate (Hay-Wells syndrome)]. / Síndrome AEC: anquilobléfaron, defecto ectodérmico, labio y paladarhendido (síndrome Hay-Wells).

A 12 month-old female is described, with clinical features of AEC syndrome. This case is a novo mutation. Clinical diagnosis at an early age is emphasised to get a better management and genetic counseling. Also we review the literature.

[Congenital contractural arachnodactyly. Report of 2 clinical cases]. / Aracnodactilia contractural congénita. Informe de dos casos clínicos.

Two unrelated male children, aged 15 and 2 months, with congenital contractural arachnodactyly (CCA) are described. CCA is an autosomal dominant disorder of benign evolution, affects the connective tissue and its morphologic phenotype is similar to Marfan syndrome. Differential diagnosis and management are discussed.

The 22q distal trisomy syndrome in a recombinant child.

A 4-month-old male infant with 22q distal trisomy and karyotype 46,XY,rec(22), dup q,inv(22)(q13q12)mat is reported. This and six previous similar instances are compared, and a distinct syndrome is delineated as follows: growth and psychomotor retardation, microcephaly or hydrocephaly, brain malformation, defective skull ossification, hypertelorism, narrow palpebral fissures, short broad nose, cleft palate with or without lip involvement, short neck, cardiac defect, renal and genital hypoplasia, osteoarticular abnormalities (mostly clubfoot), and poor survival. In addition, this syndrome is distinct from other duplications of chromosome 22, namely the complete trisomy, the proximal trisomy, and the cat-eye phenotype.

[Prevention of coronary atherosclerosis. II: Topography and morphology of "protruding" lesions. Epidemiologic, diagnostic and therapeutic implications]. / Prevención de la aterosclerosis coronaria. II: Topografía y morfología de lesiones "protruyentes". Implicaciones epidemiológicas, diagnósticas y terapéuticas.

Topographic and morphologic aspects of coronary atherosclerotic "protruding" lesions were investigated in 119 accidental deaths in males living in Mexico City. Morphology and topography varied according to the arterial trunk studied and age. Left anterior descending and circumflex lesions were almost always confined to the initial 5 cms and if a lesion was present after the 3rd cm there was always a proximal lesion. Right coronary lesions occasionally were found distally even in the absence of proximal lesions. Third decade lesions were usually not calcified. Stenosis if present was rarely multivascular. Some fourth decade lesions were calcified; plurivascular stenosis was present in some cases. Fifth decade lesions show sequential stenotic lesions in the same vessel; calcium and plurivascular stenosis were often observed. However the features observed in the 3rd decade could be observed in the older subjects. Reference is made to lesions which are found in both the left main trunk and the left anterior descending. Epidemiological and clinical applications related with preventive programs are mentioned.