Synergistic neuroprotective action of prolactin and 17ß-estradiol on kainic acid-induced hippocampal injury and long-term memory deficit in ovariectomized rats.

PURPOSE: The neuroprotective actions of the ovarian hormone 17ß-estradiol (E2) against different brain lesions have been constantly confirmed in a variety of models including kainic acid (KA) lesions. Similarly, the pituitary hormone prolactin (PRL), traditionally associated with lactogenesis, has recently been linked to a large diversity of functions, including neurogenesis, neuroprotection, and cognitive processes. While the mechanisms of actions of E2 as regards its neuroprotective and behavioral effects have been extensively explored, the molecular mechanisms of PRL related to these roles remain under investigation. The current study aimed to investigate whether the simultaneous administration of PRL and a low dose of E2 prevents the KA-induced cognitive deficit and if this action is associated with changes in hippocampal neuronal density. METHODS: Ovariectomized (OVX) rats were treated with saline, PRL, and/or E2 in the presence or absence of KA. Neuroprotection was assessed by Nissl staining and neuron counting. Memory was evaluated with the novel object recognition test (NOR). RESULTS: On their own, both PRL and E2 prevented short- and long-term memory deficits in lesioned animals and exerted neuroprotection against KA-induced excitotoxicity in the hippocampus. Interestingly, the combined hormonal treatment was superior to either of the treatments administered alone as regards improving both memory and neuronal survival. CONCLUSION: Taken together, these results point to a synergic effect of E2 and PRL in the hippocampus to produce their behavioral, proliferative, and neuroprotective effects.

Class I histone deacetylases inhibition reverses memory impairment induced by acute stress in mice.

While chronic stress induces learning and memory impairments, acute stress may facilitate or prevent memory consolidation depending on whether it occurs during the learning event or before it, respectively. On the other hand, it has been shown that histone acetylation regulates long-term memory formation. This study aimed to evaluate the effect of two inhibitors of class I histone deacetylases (HDACs), 4-phenylbutyrate (PB) and IN14 (100 mg/kg/day, ip for 2 days), on memory performance in mice exposed to a single 15-min forced swimming stress session. Plasma corticosterone levels were determined 30 minutes after acute swim stress in one group of mice. In another experimental series, independent groups of mice were trained in one of three different memory tasks: Object recognition test, Elevated T maze, and Buried food location test. Subsequently, the hippocampi were removed to perform ELISA assays for histone deacetylase 2 (HDAC2) expression. Acute stress induced an increase in plasma corticosterone levels, as well as hippocampal HDAC2 content, along with an impaired performance in memory tests. Moreover, PB and IN14 treatment prevented memory loss in stressed mice. These findings suggest that HDAC2 is involved in acute stress-induced cognitive impairment. None of the drugs improved memory in non-stressed animals, indicating that HDACs inhibitors are not cognitive boosters, but rather potentially useful drugs for mitigating memory deficits.

Modulation of Kynurenic Acid Production by N-acetylcysteine Prevents Cognitive Impairment in Adulthood Induced by Lead Exposure during Lactation in Mice.

Lead (Pb2+) exposure during early life induces cognitive impairment, which was recently associated with an increase in brain kynurenic acid (KYNA), an antagonist of NMDA and alpha-7 nicotinic receptors. It has been described that N-acetylcysteine (NAC) favors an antioxidant environment and inhibits kynurenine aminotransferase II activity (KAT II, the main enzyme of KYNA production), leading to brain KYNA levels decrease and cognitive improvement. This study aimed to investigate whether the NAC modulation of the brain KYNA levels in mice ameliorated Pb2+-induced cognitive impairment. The dams were divided into four groups: Control, Pb2+, NAC, and Pb2++NAC, which were given drinking water or 500 ppm lead acetate in the drinking water ad libitum, from 0 to 23 postnatal days (PNDs). The NAC and Pb2++NAC groups were simultaneously fed NAC (350 mg/day) in their chow from 0 to 23 PNDs. At PND 60, the effect of the treatment with Pb2+ and in combination with NAC on learning and memory performance was evaluated. Immediately after behavioral evaluation, brain tissues were collected to assess the redox environment; KYNA and glutamate levels; and KAT II activity. The NAC treatment prevented the long-term memory deficit exhibited in the Pb2+ group. As expected, Pb2+ group showed redox environment alterations, fluctuations in glutamate levels, and an increase in KYNA levels, which were partially avoided by NAC co-administration. These results confirmed that the excessive KYNA levels induced by Pb2+ were involved in the onset of cognitive impairment and could be successfully prevented by NAC treatment. NAC could be a tool for testing in scenarios in which KYNA levels are associated with the induction of cognitive impairment.

Evidence of long-term allocentric spatial memory in the Terrestrial Hermit Crab Coenobita compressus.

Spatial learning is a complex cognitive skill and ecologically important trait scarcely studied in crustaceans. We investigated the ability of the Pacific (Ecuadorian) hermit crab Coenobita compressus, to learn an allocentric spatial task using a palatable novel food as reward. Crabs were trained to locate the reward in a single session of eleven consecutive trials and tested subsequently, for short- (5 min) and long-term memory 1, 3 and 7 days later. Our results indicate that crabs were able to learn the location of the reward as they showed a reduction in the time required to find the food whenever it was present, suggesting a visuo-spatial and olfactory cue-guided task resolution. Moreover, crabs also remember the location of the reward up to 7 days after training using spatial cues only (without the food), as evidenced by the longer investigation time they spent in the learned food location than in any other part of the experimental arena, suggesting a visuo-spatial memory formation. This study represents the first description of allocentric spatial long-term memory in a terrestrial hermit crab.

Pregestational Exposure to T. gondii Produces Maternal Antibodies That Recognize Fetal Brain Mimotopes and Induces Neurochemical and Behavioral Dysfunction in the Offspring.

The activation of the maternal immune system by a prenatal infection is considered a risk factor for developing psychiatric disorders in the offspring. Toxoplasma gondii is one of the pathogenic infections associated with schizophrenia. Recent studies have shown an association between high levels of IgG anti-T. gondii from mothers and their neonates, with a higher risk of developing schizophrenia. The absence of the parasite and the levels of IgGs found in the early stages of life suggest a transplacental transfer of the anti-T. gondii IgG antibodies, which could bind fetal brain structures by molecular mimicry and induce alterations in neurodevelopment. This study aimed to determine the maternal pathogenic antibodies formation that led to behavioral impairment on the progeny of rats immunized with T. gondii. Female rats were immunized prior to gestation with T. gondii lysate (3 times/once per week). The anti-T. gondii IgG levels were determined in the serum of pregestational exposed females' previous mating. After this, locomotor activity, cognitive and social tests were performed. Cortical neurotransmitter levels for dopamine and glutamate were evaluated at 60 PND in the progeny of rats immunized before gestation (Pregestational group). The maternal pathogenic antibodies were evidenced by their binding to fetal brain mimotopes in the Pregestational group and the reactivity of the serum containing anti-T. gondii IgG was tested in control fetal brains (non-immunized). These results showed that the Pregestational group presented impairment in short and long-term memory, hypoactivity and alteration in social behavior, which was also associated with a decrease in cortical glutamate and dopamine levels. We also found the IgG antibodies bound to brain mimotopes in fetuses from females immunized with T. gondii, as well as observing a strong reactivity of the serum females immunized for fetal brain structures of fetuses from unimmunized mothers. Our results suggest that the exposure to T. gondii before gestation produced maternal pathogenic antibodies that can recognize fetal brain mimotopes and lead to neurochemical and behavioral alterations in the offspring.

Juvenile Exposure to BPA Alters the Estrous Cycle and Differentially Increases Anxiety-like Behavior and Brain Gene Expression in Adult Male and Female Rats.

Perinatal exposure to bisphenol A (BPA) in murine models has been reported to affect social behavior and increase anxiety. However, there is little information about the effects of BPA exposure during puberty, a period in which sex hormones influence the maturation and differentiation of the brain. In this work, we evaluated the effect of BPA administration during the juvenile stage (PND 21-50) on anxiety in male and female rats. Newly weaned Wistar rats were treated with BPA (0, 50, or 500 µg/kg/day) for 30 days. To compare the intra- and inter-sex behavioral profiles, rats were evaluated using four different anxiety models: the Open field test (OFT), the Elevated plus maze (EPM), the Light-dark box test (LDBT), and the Defensive burying test (DBT). Males exhibited a clear-cut anxious profile at both doses in all four tests, while no clear behavioral effect of BPA exposure was observed in female rats. The latter showed an altered estrous cycle that initiated earlier in life and had a shorter duration, with the estrous phase predominating. Moreover, the expression of ESR1, ESR2, GABRA1, GRIN1, GR, MR, and AR genes increased in the hippocampus and hypothalamus of male rats treated with 50 µg/kg, but not in females. Our results indicate that BPA consistently induces a higher anxiety profile in male than in female rats, as evidenced predominantly by an increase in passive-coping behaviors and changes in brain gene expression, highlighting the importance of sex in peripubertal behavioral toxicology studies.

The 5-HT6R agonist E-6837 and the antagonist SB-271046 reverse the psychotic-like behaviors induced by ketamine.

Schizophrenia is a serious mental disorder that affects 1% of the world's population. Although various therapeutic tools have been developed since the appearance of the first generation of antipsychotics, the effect of these agents does not manage to attenuate a significant part of psychotic symptoms. Ketamine is an anesthetic agent able to produce psychotic-like symptoms through the antagonism of the glutamatergic N-methyl-d-aspartic acid (NMDA) receptors (NMDARs). This drug has been widely used to study new pharmacological tools with potential antipsychotic properties. On the contrary, it is known that the 5-HT6 receptor agonist and antagonist drugs induce procognitive, anxiolytic and antidepressant effects in different preclinical models. Therefore, the aim of this study was to evaluate the behavioral actions of the 5-HT6 receptors' agonist E-6837 and the antagonist SB-271046, in ICR-CD1 mice previously treated with a subchronic ketamine scheme (10 mg/kg i.p. daily for 5 days). Results showed that repeated administration of ketamine induced recognition memory deficit, anxiogenic effects, obsessive-compulsive behaviors and stereotyped movements. The acute administration of both 5-HT6 agents reversed the memory deficit and induced a decrease in anxiety, whereas SB-271046 administration produced a decrease in climbing behavior. The injection of either of these 5-HT6 drugs had no effect in the light-dark test. Surprisingly, when these drugs were injected together with ketamine, anxiogenic actions were produced. Current findings suggest that both agonist and antagonist 5-HT6 drugs play an important role in modulating psychotic-like symptoms induced by the subchronic blockade of NMDAR.

Cirugía bariátrica y trastorno por abuso de alcohol y otras sustancias: una revisión sistemática / Bariatric surgery and alcohol and substance abuse disorder: A systematic review

Antecedentes: La cirugía bariátrica es un procedimiento quirúrgico relativamente seguro y con alta tasa de éxito. Sin embargo, reportes recientes indican una mayor prevalencia de abuso de alcohol u otras sustancias en este grupo de pacientes. El propósito del presente estudio fue revisar la evidencia que existe al respecto para que sea tomada en cuenta por el equipo multidisciplinario que atiende a este grupo de pacientes. Métodos: Se realizaron búsquedas en las bases de datos de PubMed y CENTRAL, y se extrajeron las razones de momio de los distintos artículos, comparando la prevalencia por abuso de alcohol o de otras sustancias en el periodo posquirúrgico vs. los niveles prequirúrgicos. También se comparó la prevalencia de abuso de alcohol tras distintos tipos de cirugía bariátrica. Resultados: Un total de 49.121 pacientes bariátricos (80,8% mujeres) fueron evaluados para abuso de alcohol. De manera general, se encontró que la cirugía bariátrica estaba asociada con un aumento en la prevalencia por abuso de alcohol (4,58±5,3 vs. 1,58±10,7% en el periodo prequirúrgico). También encontramos que la población de pacientes que se sometieron a cirugía de tipo RYGB tenía mayor prevalencia de abuso de alcohol que aquellos que se sometieron a otro tipo de cirugía (OR: 1,83; IC 95%: 1,51-2,21). La prevalencia de abuso de sustancias distintas al alcohol tras este procedimiento está menos estudiada, aunque parece existir un aumento en el riesgo por abuso a ciertas sustancias. Conclusiones: La cirugía bariátrica es el mejor tratamiento para la obesidad y sus complicaciones. La evidencia revisada sugiere que se relaciona con un aumento modesto, pero consistente en la prevalencia por abuso de alcohol y otras sustancias. El equipo médico a cargo del paciente bariátrico deberá estar informado acerca de esta eventualidad para su oportuna prevención, diagnóstico y tratamiento. (AU)

Introduction: Bariatric surgery is a relatively safe surgical procedure with a high success rate. However, recent reports indicate a higher prevalence of alcohol or substance abuse disorder in this patient group. The purpose of this study was to review the related evidence to serve as a reference for multidisciplinary teams who treat these patients. Methods: We searched the PubMed and CENTRAL databases. The odds ratios were extracted from the different articles, comparing the prevalence of the abuse of alcohol or other substances in the postoperative period versus preoperative levels. We also compared the prevalence of alcohol use disorder after different types of bariatric surgery. Results: A total of 49 121 bariatric patients (80.8% female) were evaluated for alcohol use disorder. In general, bariatric surgery was found to be associated with an increase in the prevalence of alcohol abuse (4.58±5.3 vs. 1.58±10.7% in the preoperative period). We also found that the population of patients who underwent RYGB procedures had a higher prevalence of alcohol use disorder than patients who underwent another type of surgery (OR: 1.83; 95% CI: 1.51-2.21). The prevalence of substance abuse disorder (other than alcohol) after this procedure is less studied, although there appears to be an increased risk of abuse of certain substances. Conclusions: Bariatric surgery is the best treatment for obesity and its complications. The evidence reviewed suggests that it correlates with a modest but consistent increase in the prevalence of abuse of alcohol and other substances. Medical teams who treat bariatric patients must be informed about this eventuality for its timely prevention, diagnosis and treatment. (AU)

Bariatric surgery and alcohol and substance abuse disorder: A systematic review.

INTRODUCTION: Bariatric surgery is a relatively safe surgical procedure with a high success rate. However, recent reports indicate a higher prevalence of alcohol or substance abuse disorder in this patient group. The purpose of this study was to review the related evidence to serve as a reference for multidisciplinary teams who treat these patients. METHODS: We searched the PubMed and CENTRAL databases. The odds ratios were extracted from the different articles, comparing the prevalence of the abuse of alcohol or other substances in the postoperative period versus preoperative levels. We also compared the prevalence of alcohol use disorder after different types of bariatric surgery. RESULTS: A total of 49 121 bariatric patients (80.8% female) were evaluated for alcohol use disorder. In general, bariatric surgery was found to be associated with an increase in the prevalence of alcohol abuse (4.58 ± 5.3 vs. 1.58 ± 10.7% in the preoperative period). We also found that the population of patients who underwent RYGB procedures had a higher prevalence of alcohol use disorder than patients who underwent another type of surgery (OR: 1.83; 95% CI: 1.51-2.21). The prevalence of substance abuse disorder (other than alcohol) after this procedure is less studied, although there appears to be an increased risk of abuse of certain substances. CONCLUSIONS: Bariatric surgery is the best treatment for obesity and its complications. The evidence reviewed suggests that it correlates with a modest but consistent increase in the prevalence of abuse of alcohol and other substances. Medical teams who treat bariatric patients must be informed about this eventuality for its timely prevention, diagnosis and treatment.

Corrigendum: Cognitive Impairment After Resolution of Hepatic Encephalopathy: A Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.3389/fnins.2021.579263.].

Bariatric surgery and alcohol and substance abuse disorder: A systematic review. / Cirugía bariátrica y trastorno por abuso de alcohol y otras sustancias: una revisión sistemática.

INTRODUCTION: Bariatric surgery is a relatively safe surgical procedure with a high success rate. However, recent reports indicate a higher prevalence of alcohol or substance abuse disorder in this patient group. The purpose of this study was to review the related evidence to serve as a reference for multidisciplinary teams who treat these patients. METHODS: We searched the PubMed and CENTRAL databases. The odds ratios were extracted from the different articles, comparing the prevalence of the abuse of alcohol or other substances in the postoperative period versus preoperative levels. We also compared the prevalence of alcohol use disorder after different types of bariatric surgery. RESULTS: A total of 49 121 bariatric patients (80.8% female) were evaluated for alcohol use disorder. In general, bariatric surgery was found to be associated with an increase in the prevalence of alcohol abuse (4.58±5.3 vs. 1.58±10.7% in the preoperative period). We also found that the population of patients who underwent RYGB procedures had a higher prevalence of alcohol use disorder than patients who underwent another type of surgery (OR: 1.83; 95% CI: 1.51-2.21). The prevalence of substance abuse disorder (other than alcohol) after this procedure is less studied, although there appears to be an increased risk of abuse of certain substances. CONCLUSIONS: Bariatric surgery is the best treatment for obesity and its complications. The evidence reviewed suggests that it correlates with a modest but consistent increase in the prevalence of abuse of alcohol and other substances. Medical teams who treat bariatric patients must be informed about this eventuality for its timely prevention, diagnosis and treatment.

Short-term memory reactivation of a weak CS-US association promotes long-term memory persistence in conditioned odor aversion.

In conditioned odor aversion (COA), the association of a tasteless odorized solution (the conditioned stimulus [CS]) with an intraperitoneal injection of LiCl (the unconditioned stimulus [US[), which produces visceral malaise, results in its future avoidance. The strength of this associative memory is mainly dependent on two parameters, that is, the strength of the US and the interstimuli interval (ISI). In rats, COA has been observed only with ISIs of ≤15 min and LiCl (0.15 M) doses of 2.0% of bodyweight, when tested 48 h after acquisition (long-term memory [LTM]). However, we previously reported a robust aversion in rats trained with ISIs up to 60 min when tested 4 h after acquisition (short-term memory [STM]). Since memories get reactivated during retrieval, in the current study we hypothesized that testing for STM would reactivate this COA trace, strengthening its LTM. For this, we compared the LTM of rats trained with long ISIs or low doses of LiCl initially tested for STM with that of rats tested for LTM only. Interestingly, rats conditioned under parameters sufficient to produce STM, but not LTM, showed a reliable LTM when first tested for STM. These observations suggest that under suboptimal training conditions, such as long ISIs or low US intensities, a CS-US association is established but requires reactivation in the short-term in order to persist in the long-term.

Cognitive Impairment After Resolution of Hepatic Encephalopathy: A Systematic Review and Meta-Analysis.

Hepatic encephalopathy (HE) is one of the most disabling metabolic diseases. It consists of a complication of liver disease through the action of neurotoxins, such as excessive production of ammonia from liver, resulting in impaired brain function. Its prevalence and incidence are not well known, although it has been established that up to 40% of cirrhotic patients may develop HE. Patients with HE episodes display a wide range of neurological disturbances, from subclinical alterations to coma. Recent evidence suggests that the resolution of hepatic encephalopathy does not fully restore cognitive functioning in cirrhotic patients. Therefore, the aim of this review was to evaluate the evidence supporting the presence of lingering cognitive deficits in patients with a history of HE compared to patients without HE history and how liver transplant affects such outcome in these patients. We performed two distinct meta-analysis of continuous outcomes. In both cases the results were pooled using random-effects models. Our results indicate that cirrhotic patients with a history of HE show clear cognitive deficits compared control cirrhotic patients (Std. Mean Difference (in SDs) = -0.72 [CI 95%: -0.94, -0.50]) and that these differences are not fully restored after liver transplant (Std. Mean Difference (in SDs) = -0.72 [CI 95%: -0.94, -0.50]).

Muscarinic receptor signaling in the amygdala is required for conditioned taste aversion.

The sense of taste provides information regarding the nutrient content, safety or potential toxicity of an edible. This is accomplished via a combination of innate and learned taste preferences. In conditioned taste aversion (CTA), rats learn to avoid ingesting a taste that has previously been paired with gastric malaise. Recent evidence points to a role of cholinergic muscarinic signaling in the amygdala for the learning and storage of emotional memories. The present study tested the participation of muscarinic receptors in the amygdala during the formation of CTA by infusing the non-specific antagonist scopolamine into the basolateral or central subnuclei before or after conditioning, as well as before retrieval. Our data show that regardless of the site of infusion, pre-conditioning administration of scopolamine impaired CTA acquisition whereas post-conditioning infusion did not affect its storage. Also, infusions into the basolateral but not in the central amygdala before retrieval test partially reduced the expression of CTA. Our results indicate that muscarinic receptors activity is required for acquisition but not consolidation of CTA. In addition, our data add to recent evidence pointing to a role of cholinergic signaling in peri-hippocampal structures in the process of memory retrieval.

Kynurenine Pathway as a New Target of Cognitive Impairment Induced by Lead Toxicity During the Lactation.

The immature brain is especially vulnerable to lead (Pb2+) toxicity, which is considered an environmental neurotoxin. Pb2+ exposure during development compromises the cognitive and behavioral attributes which persist even later in adulthood, but the mechanisms involved in this effect are still unknown. On the other hand, the kynurenine pathway metabolites are modulators of different receptors and neurotransmitters related to cognition; specifically, high kynurenic acid levels has been involved with cognitive impairment, including deficits in spatial working memory and attention process. The aim of this study was to evaluate the relationship between the neurocognitive impairment induced by Pb2+ toxicity and the kynurenine pathway. The dams were divided in control group and Pb2+ group, which were given tap water or 500 ppm of lead acetate in drinking water ad libitum, respectively, from 0 to 23 postnatal day (PND). The poison was withdrawn, and tap water was given until 60 PND of the progeny. The locomotor activity in open field, redox environment, cellular function, kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK) levels as well as kynurenine aminotransferase (KAT) and kynurenine monooxygenase (KMO) activities were evaluated at both 23 and 60 PND. Additionally, learning and memory through buried food location test and expression of KAT and KMO, and cellular damage were evaluated at 60 PND. Pb2+ group showed redox environment alterations, cellular dysfunction and KYNA and 3-HK levels increased. No changes were observed in KAT activity. KMO activity increased at 23 PND and decreased at 60 PND. No changes in KAT and KMO expression in control and Pb2+ group were observed, however the number of positive cells expressing KMO and KAT increased in relation to control, which correlated with the loss of neuronal population. Cognitive impairment was observed in Pb2+ group which was correlated with KYNA levels. These results suggest that the increase in KYNA levels could be a mechanism by which Pb2+ induces cognitive impairment in adult mice, hence the modulation of kynurenine pathway represents a potential target to improve behavioural alterations produced by this environmental toxin.

Biochemical and Behavioral Characterization of IN14, a New Inhibitor of HDACs with Antidepressant-Like Properties.

Evidence suggests that histone deacetylases (HDACs) inhibitors could be used as an effective treatment for some psychiatric and neurological conditions such as depression, anxiety and age-related cognitive decline. However, non-specific HDAC inhibiting compounds have a clear disadvantage regarding their efficacy and safety, thus the need to develop more selective ones. The present study evaluated the toxicity, the capacity to inhibit HDAC activity and antidepressant-like activity of three recently described class I HDAC inhibitors IN01, IN04 and IN14, using A.salina toxicity test, in vitro fluorometric HDAC activity assay and forced-swimming test, respectively. Our data show that IN14 possesses a better profile than the other two. Therefore, the pro-cognitive and antidepressant effects of IN14 were evaluated. In the forced-swimming test model of depression, intraperitoneal administration of IN14 (100 mg/Kg/day) for five days decreased immobility, a putative marker of behavioral despair, significantly more than tricyclic antidepressant desipramine, while also increasing climbing behavior, a putative marker of motivational behavior. On the other hand, IN14 left the retention latency in the elevated T-maze unaltered. These results suggest that novel HDAC class I inhibitor IN14 may represent a promising new antidepressant with low toxicity and encourages further studies on this compound.

Obesidad, síndrome metabólico y percepción olfativa / Obesity, metabolic syndrome and olfactory perception

En la actualidad, la obesidad y el síndrome metabólico son enfermedades que representan un grave problema global de salud pública. A consecuencia de ello, en las últimas décadas ha aumentado el interés por estudiar los efectos de estas patologías sobre el funcionamiento del sistema nervioso central. Uno de los aspectos más ignorados en la bibliografía ha sido el impacto que tienen sobre los sistemas sensoriales, entre los que se encuentra el olfato. El sistema olfativo se relaciona con distintas funciones vitales, como activar mecanismos de defensa, contribuir a la inducción de reflejos apetitivos y digestivos, y reconocer individuos de su misma especie, e incluso tiene implicaciones sociosexuales. Se sabe que, además, desempeña un papel importante en la ingesta de alimentos, en la decisión de lo que se va a consumir, en los mecanismos de apetito y saciedad y, por ende, está involucrado en el desarrollo de obesidad. Estudios clínicos han demostrado que pacientes con obesidad presentan hiposmia con mayor frecuencia en comparación con sujetos delgados de la misma edad. También se han encontrado alteraciones en el olfato de roedores que presentan obesidad o rasgos similares a los del síndrome metabólico del humano. Las causas por las cuales existe esta asociación apenas están comenzando a investigarse; en este trabajo se revisan los estudios que han intentado entenderla desde un enfoque clínico y preclínico, así como los mecanismos biológicos que hasta el momento se han explorado en la bibliografía

Nowadays, it is well accepted that obesity and metabolic syndrome are diseases that constitute a global public health issue. In consequence, the interest in the study of the effects these pathologies produce in the central nervous system has greatly increased in the last decades. One of the most overlooked topics in the literature is the impact they exert in sensory systems, among which is olfaction. The olfactory system is related to a number of vital functions, like the activation of defense mechanisms, contribution to appetitive and digestive reflexes, recognition of conspecifics, and even has socio-sexual implications. It has been discovered that the olfactory system also plays a crucial role in food intake, the choice of foods, appetite and satiety mechanisms; therefore, it is involved in obesity development. Clinical studies have proven that obese patients exhibit hyposmia more frequently than aged-matched healthy controls. Olfactory alterations have also been found in obese rodents or in animals with similar features of human metabolic syndrome. The causes of this association are still being investigated. This work reviews the studies that have tried to understand this association from a preclinical and clinical approach as well as those biological mechanisms that could be involved. The evidences here presented suggest that obesity and metabolic syndrome affect the adequate function of olfactory sensory system

Cyclic changes and actions of progesterone and allopregnanolone on cognition and hippocampal basal (stratum oriens) dendritic spines of female rats.

Ovarian steroids modulate the neuronal structure and function during the estrous cycle, contrasting peak effects during the proestrus cycle and low effects during the metestrus cycle. An ovariectomy (OVX) decreases gonadal hormones and tests the effects of substitutive therapies. We studied female rats with a normal estrous cycle and we also studied the effects of systemic progesterone (P4, 4.0 mg/kg) or its reduced metabolite allopregnanolone (ALLO, 4.0 mg/kg, both for 10 days) in females who had had an OVX 16.5 weeks prior to the study (long-term OVX) with the novel object recognition test (NORT) for associative memory. The dendritic shape and spine density in Golgi-impregnated basal dendrites (stratum oriens) of hippocampal pyramidal neurons was also studied. Proestrus females had a better performance than metestrus or OVX females in short-term memory (tested 1 h after the acquisition phase). Proestrus and metestrus females showed better results than OVX females for long-term memory (24 h after the initial phase). Both P4 and ALLO recovered the cognitive impairment induced by long-term OVX. Also, proestrus females had a higher density of dendritic spines than metestrus females, OVX reduced the density of spines when compared to intact females, whereas both P4 and ALLO treatments increased the dendritic spine density, number of dendritic branches along the dendritic length, and branching order compared to vehicle. These data add the dendrites of the stratum oriens as an additional site for naturally occurring changes in spine density during the estrous cycle and evidence the actions of progestins in both behavioral recovery and the structural dendritic rearrangement of hippocampal pyramidal neurons in long-term OVX female rats.

Seaweeds-derived compounds modulating effects on signal transduction pathways: A systematic review.

BACKGROUND: Recently, the study of marine natural products has gained interest due to their relevant biological activities. Specially, seaweeds produce bioactive compounds that could act as modulators of cell signaling pathways involved in a plethora of diseases. Thereby, the description of the molecular mechanisms by which seaweeds elicit its biological functions will certainly pave the way to the pharmacological development of drugs. AIM: This review describes the molecular mechanisms by which seaweeds act and its possible utilization in the design of new drugs. METHODS: This review was conducted according to the PRISMA-P guidelines for systematic reviews. Two independent authors searched into four different databases using combinations of keywords. Two more authors selected the articles following the eligibility criteria. Information extraction was conducted by two separated authors and entered into spreadsheets. Methodological quality and risk of bias were determined applying a 12-question Risk of Bias criteria tool. RESULTS AND DISCUSSION: We found 2360 articles (SCOPUS: 998; PubMed: 678; Wiley: 645 and EBSCO: 39) using the established keywords, of which 113 articles fit the inclusion criteria and were included in the review. This work comprises studies in cell lines, and animal models, any clinical trial was excluded. The articles were published from 2005 up to March 31st 2018. The biggest amount of articles was published in 2017. Furthermore, the seaweeds tested in the studies were collected in 15 countries, mainly in Eastern countries. We found that the main modulated signaling pathways by seaweeds-derivate extracts and compounds were: L-Arginine/NO, TNF-α, MAPKs, PI3K/AKT/GSK, mTOR, NF-κB, extrinsic and intrinsic apoptosis, cell cycle, MMPs and Nrf2. Finally, the articles we analyzed showed moderate risk of bias in almost all the parameters evaluated. However, the studies fail to describe the place and characteristics of sample collection, the sample size, and the blindness of the experimental design. CONCLUSION: In this review we identified and summarized relevant information related to seaweed-isolated compounds and extracts having biological activity; their role in different signal pathways to better understand their potential to further development of cures for cancer, diabetes, and inflammation-related diseases.

NMDA receptor and nitric oxide synthase activity in the central amygdala is involved in the acquisition and consolidation of conditioned odor aversion.

Rats readily learn to avoid a tasteless odorized solution if they experience visceral malaise after consuming it. This phenomenon is referred to as conditioned odor aversion (COA). Several studies have shown that COA depends on the functional integrity of the amygdala, with most studies focusing on the basolateral nucleus. On the other hand, the role of the central amygdala (CeA) which is known to be involved in the consolidation of conditioned taste aversion (CTA) remains to be established. To address this issue, we evaluated the effect of inhibiting NMDA receptor activity in this structure on COA memory formation. Intra-CeA infusions of non-competitive NMDA receptor inhibitor MK-801 prevented memory formation both when administered before and up to 15 min after COA conditioning, while no effect of this drug was observed when given before long-term memory test. We next evaluated the role of one of the main downstream effectors of brain NMDA receptor signaling, nitric oxide synthase (NOS), known to play a key role in a wide variety learning tasks including some types of olfactory conditioning. Similar results were obtained with inhibition of either NOS or neuron-specific NOS; which proved to be required both during and after COA training, though for a shorter time span than NMDA receptors. Also, neither isoform showed to be required to memory retrieval. These results suggest that the US signaling during acquisition and the initial consolidation step of COA depends on glutamate-NO system activation in the CeA.