0000000000075987
AUTHOR
Rafael Maldonado
Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling.
Cognitive impairment is one of the most important negative consequences associated with cannabis consumption. We found that CB1 cannabinoid receptor (CB1R) activation transiently modulated the mammalian target of rapamycin (mTOR)/p70S6K pathway and the protein synthesis machinery in the mouse hippocampus, which correlated with the amnesic properties of delta9-tetrahydrocannabinol (THC). In addition, non-amnesic doses of either the mTOR blocker rapamycin or the protein synthesis inhibitor anisomycin abrogated the amnesic-like effects of THC, pointing to a mechanism involving new protein synthesis. Moreover, using pharmacological and genetic tools, we found that THC long-term memory deficits …
Peripheral and central CB1 cannabinoid receptors control stress-induced impairment of memory consolidation
Stressful events can generate emotional memories linked to the traumatic incident, but they also can impair the formation of nonemotional memories. Although the impact of stress on emotional memories is well studied, much less is known about the influence of the emotional state on the formation of nonemotional memories. We used the novel object-recognition task as a model of nonemotional memory in mice to investigate the underlying mechanism of the deleterious effect of stress on memory consolidation. Systemic, hippocampal, and peripheral blockade of cannabinoid type-1 (CB1) receptors abolished the stress-induced memory impairment. Genetic deletion and rescue of CB1 receptors in specific ce…
Additional file 2 of Gut bacterial ClpB-like gene function is associated with decreased body weight and a characteristic microbiota profile
Additional file 2. Alignments of the mimetic amino acid motif of the α-MSH, the ClpB from E. coli str K12 and the predicted ORFs from each sequence of the samples 1, 30 and 143.
Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways
Gut: first published.
Gut bacterial ClpB-like gene function is associated with decreased body weight and a characteristic microbiota profile
[Background]: The chaperone ClpB, a bacterial protein, is a conformational antigen-mimetic of α-melanocyte-stimulating hormone (α-MSH) implicated in body weight regulation in mice. We here investigated the potential associations of gut bacterial ClpB-like gene function with obesity status and gut microbiota in humans.
Presence of Blastocystis in gut microbiota is associated with cognitive traits and decreased executive function.
Growing evidence implicates the gut microbiome in cognition. Blastocystis is a common gut single-cell eukaryote parasite frequently detected in humans but its potential involvement in human pathophysiology has been poorly characterized. Here we describe how the presence of Blastocystis in the gut microbiome was associated with deficits in executive function and altered gut bacterial composition in a discovery (n = 114) and replication cohorts (n = 942). We also found that Blastocystis was linked to bacterial functions related to aromatic amino acids metabolism and folate-mediated pyrimidine and one-carbon metabolism. Blastocystis-associated shifts in bacterial functionality translated into …
Peripheral CB1 receptor blockade acts as a memory enhancer through an adrenergic-dependent mechanism
Peripheral inputs to the brain continuously shape its function and can influence the formation of non-emotional memory, but the underlying mechanisms have not been fully understood. Cannabinoid type-1 receptors (CB1R), widely distributed in the organism, is a well-recognized player in memory performance, and its systemic modulation significantly influences memory function. By assessing non-emotional memory in mice, we have now found a relevant role of peripheral CB1R in the formation of persistent memory. Indeed, peripherally restricted CB1R antagonism by using AM6545 showed a mnemonic effect that was occluded in adrenalectomized mice, after peripheral adrenergic blockade, or when vagus ner…
Additional file 1 of Gut microbiota steroid sexual dimorphism and its impact on gonadal steroids: influences of obesity and menopausal status
Additional file 1: Supplementary Table 1. Clinical characteristics of subjects after 1-year follow-up according to the gender and menopausal status.
Additional file 5 of Gut microbiota steroid sexual dimorphism and its impact on gonadal steroids: influences of obesity and menopausal status
Additional file 5: Supplementary Table 5. MRM parameters for determination of steroids and isotopically labelled standards by LC–MS/MS.
Gut microbiota steroid sexual dimorphism and its impact on gonadal steroids: influences of obesity and menopausal status
[Background]: Gonadal steroid hormones have been suggested as the underlying mechanism responsible for the sexual dimorphism observed in metabolic diseases. Animal studies have also evidenced a causal role of the gut microbiome and metabolic health. However, the role of sexual dimorphism in the gut microbiota and the potential role of the microbiome in influencing sex steroid hormones and shaping sexually dimorphic susceptibility to disease have been largely overlooked. Although there is some evidence of sex-specific differences in the gut microbiota diversity, composition, and functionality, the results are inconsistent. Importantly, most of these studies have not taken into account the go…
Effects of repeated social defeat on adolescent mice on cocaine-induced CPP and self-administration in adulthood: integrity of the blood-brain barrier
Social stress in adulthood enhances cocaine self-administration, an effect that has been related with an increase in extracellular signal-regulated kinase and p38α mitogen-activated protein kinase phosphorylation. A detrimental effect of cocaine on blood-brain barrier (BBB) integrity has also been reported. This study evaluates the effects of repeated social defeat (RSD) during adolescence on the reinforcing and motivational effects of cocaine in adult mice and the changes induced by RSD on BBB permeability. Cocaine self-administration, conditioned place preference and quantitative analysis of claudin-5, laminin, collagen-IV and IgG immunoreactivity took place 3 weeks after RSD. Mice social…
A specific prelimbic-nucleus accumbens pathway controls resilience versus vulnerability to food addiction
Food addiction is linked to obesity and eating disorders and is characterized by a loss of behavioral control and compulsive food intake. Here, using a food addiction mouse model, we report that the lack of cannabinoid type-1 receptor in dorsal telencephalic glutamatergic neurons prevents the development of food addiction-like behavior, which is associated with enhanced synaptic excitatory transmission in the medial prefrontal cortex (mPFC) and in the nucleus accumbens (NAc). In contrast, chemogenetic inhibition of neuronal activity in the mPFC-NAc pathway induces compulsive food seeking. Transcriptomic analysis and genetic manipulation identified that increased dopamine D2 receptor express…
Role of CB2 cannabinoid receptors in the rewarding, reinforcing, and physical effects of nicotine.
This study was aimed to evaluate the involvement of CB2 cannabinoid receptors (CB2r) in the rewarding, reinforcing and motivational effects of nicotine. Conditioned place preference (CPP) and intravenous self-administration experiments were carried out in knockout mice lacking CB2r (CB2KO) and wild-type (WT) littermates treated with the CB2r antagonist AM630 (1 and 3 mg/kg). Gene expression analyses of tyrosine hydroxylase (TH) and α3- and α4-nicotinic acetylcholine receptor subunits (nAChRs) in the ventral tegmental area (VTA) and immunohistochemical studies to elucidate whether CB2r colocalized with α3- and α4-nAChRs in the nucleus accumbens and VTA were performed. Mecamylamine-precipitat…
Additional file 3 of Gut microbiota steroid sexual dimorphism and its impact on gonadal steroids: influences of obesity and menopausal status
Additional file 3: Supplementary Table 3. DESeq2 results for the differential expressed bacterial taxa between post-menopausal women and men.
Additional file 2 of Gut microbiota steroid sexual dimorphism and its impact on gonadal steroids: influences of obesity and menopausal status
Additional file 2: Supplementary Table 2. DESeq2 results for the differential expressed bacterial taxa between pre-menopausal women and men.
Additional file 6 of Gut microbiota steroid sexual dimorphism and its impact on gonadal steroids: influences of obesity and menopausal status
Additional file 6: Supplementary Figure 1. Associations of gut microbiota composition in non-obese and obese subjects and bacterial families with gender and menopause status. Alpha diversity indices in a) non-obese and b) obese individuals. Beta diversity in non-obese subjects measured by c)Bray-Curtis and d) weighted unifrac. Beta diversity in obese subjects measured by e) Bray-Curtis and f) weighted unifrac. Overall differences in the microbiome composition among groups were assessed by PERMANOVA using 1000 permutations and pairwise differences between groups were assessed using the pairwise.adonis function adjusted for Bonferroni correction. *,P < 0.05; **, P < 0.01.g) Volcano plot…
Additional file 4 of Gut microbiota steroid sexual dimorphism and its impact on gonadal steroids: influences of obesity and menopausal status
Additional file 4: Supplementary Table 4. DESeq2 results for the differential expressed bacterial taxa between pre-menopausal women and post-menopausal women.
Additional file 1 of Gut bacterial ClpB-like gene function is associated with decreased body weight and a characteristic microbiota profile
Additional file 1. Top 10 bacterial taxa (family level) contributing reads to the gut bacterial ClpB-like function, in absolute and relative figures per sample.
Additional file 7 of Gut microbiota steroid sexual dimorphism and its impact on gonadal steroids: influences of obesity and menopausal status
Additional file 7: Supplementary Figure 2. Associations of gut microbiota functionality with gender and menopause status in non-obese subjects. a) Fold change for the significant differential KEGG pathways between pre-menopausal women and men, and b) pre- and post-menopausal women, identified by DESeq2 adjusting for age and obesity status. Bars are colored according to the Benjamini-Hochberg corrected p values (pFDR).
Additional file 8 of Gut microbiota steroid sexual dimorphism and its impact on gonadal steroids: influences of obesity and menopausal status
Additional file 8: Supplementary Figure 3. Gender and menopausal status differences in gonadal steroids according to the obesity status. Boxplots for the concentrations of progestin,androgens, and estrogens converted to base 10 logarithmic values. Differences among groups were analyzed by a Kruskal-Wallis test, and pair-wise comparisons were assessed by the Wilcoxon test. Significant differences are highlighted in bold italics.
Additional file 3 of Gut bacterial ClpB-like gene function is associated with decreased body weight and a characteristic microbiota profile
Additional file 3. Alignments. Alignment motif of the α-MSH and percentage of identity between the E. coli motif and the identified microbial counterparts in each sequence. Bacterial family identity: Average identity of the epitope in each bacterial family compared to the motif in E. coli as well as the distribution of families through the samples according to their degree of homology.
Additional file 9 of Gut microbiota steroid sexual dimorphism and its impact on gonadal steroids: influences of obesity and menopausal status
Additional file 9: Supplementary Figure 4. Gut microbial associations with circulating testosterone concentrations. a) Permutation tests for the goodness-of-fit (R2Y) and goodness of prediction (Q2Y) for the O-PLS model predicting plasma testosterone levels from bacterial families in non-obese individuals. b) Significant gut bacterial families identified by O-PLS modeling. c) Permutation tests for the goodness-of-fit (R2Y) and goodness of prediction (Q2Y) for the O-PLS model predicting plasma testosterone levels after 1-year follow-up from bacterial families at baseline in humans. d) Significant gut bacterial families identified by O-PLS modeling. e) Permutation tests for the goodness-of-fi…