scholarly journals Sex-Specific Effects of Synbiotic Exposure in Mice on Addictive-Like Behavioral Alterations Induced by Chronic Alcohol Intake Are Associated With Changes in Specific Gut Bacterial Taxa and Brain Tryptophan Metabolism

2021 ◽  
Vol 8 ◽  
Author(s):  
Nieves Pizarro ◽  
Elk Kossatz ◽  
Pedro González ◽  
Alba Gamero ◽  
Emma Veza ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Cognitive Deficits ◽  
Alcohol Intake ◽  
Bacterial Species ◽  
Tryptophan Metabolism ◽  
Dependent Manner ◽  
Chronic Alcohol ◽  
Male Mice ◽  
Behavioral Alterations ◽  
Uncultured Bacterium

Chronic alcohol intake has been shown to disrupt gut microbiota homeostasis, but whether microbiota modulation could prevent behavioral alterations associated with chronic alcohol intake remains unknown. We investigated the effects of synbiotic dietary supplementation on the development of alcohol-related addictive behavior in female and male mice and evaluated whether these effects were associated with changes in bacterial species abundance, short-chain fatty acids, tryptophan metabolism, and neurotransmitter levels in the prefrontal cortex and hippocampus. Chronic intermittent exposure to alcohol during 20 days induced escalation of intake in both female and male mice. Following alcohol deprivation, relapse-like behavior was observed in both sexes, but anxiogenic and cognitive deficits were present only in females. Synbiotic treatment reduced escalation and relapse to alcohol intake in females and males. In addition, the anxiogenic-like state and cognitive deficits observed in females following alcohol deprivation were abolished in mice exposed to synbiotic. Alcohol-induced differential alterations in microbial diversity and abundance in both sexes. In females, synbiotic exposure abrogated the alterations provoked by alcohol in Prevotellaceae UCG-001 and Ruminococcaceae UCG-014 abundance. In males, synbiotic exposure restored the changes induced by alcohol in Akkermansia and Muribaculum uncultured bacterium abundance. Following alcohol withdrawal, tryptophan metabolites, noradrenaline, dopamine, and γ-aminobutyric acid concentrations in the prefrontal cortex and the hippocampus were correlated with bacterial abundance and behavioral alterations in a sex-dependent manner. These results suggested that a dietary intervention with a synbiotic to reduce gut dysbiosis during chronic alcohol intake may impact differently the gut-brain-axis in females and males.

CB1R Promotes Chronic Alcohol-Induced Neuronal Necroptosis in Mice Prefrontal Cortex

2020 ◽  
Author(s):  
Lin Ye ◽  
Shuhao Li ◽  
Xiaochen Liu ◽  
Dingang Zhang ◽  
Liliang Li ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Protein Level ◽  
Cannabinoid Receptors ◽  
Alcohol Exposure ◽  
Global Burden ◽  
Dependent Manner ◽  
Chronic Alcohol ◽  
Inverse Agonists ◽  
Alcohol Vapor ◽  
Chronic Alcohol Exposure

Abstract Aims Alcohol abuse induces multiple neuropathology and causes global burden to human health. Prefrontal cortex (PFC) is one of the most susceptible regions to alcohol-induced neuropathology. However, precise mechanisms underlying these effects on PFC remain to be elucidated. Herein, we investigated whether RIP1/RIP3/MLKL-mediated necroptosis was involved in the alcohol-induced PFC injury, and explored the effect that cannabinoid receptors (CBRs) exerted on the neurotoxicity of alcohol. Methods In this study, dynamic development of neuronal necroptosis in the PFC region was monitored after 95% (v/v) alcohol vapor administration for 15 and 30 days, respectively. Selective CBRs agonists or inverse agonists were pretreated according to the experimental design. All the PFC tissues were isolated and further examined by biochemical and histopathological analyses. Results It was found that chronic alcohol exposure increased the protein level of MLKL and also the phosphorylated levels of RIP1, RIP3 and MLKL in a time-dependent manner, all of which indicated the activation of necroptosis signaling. Particularly, compared to astrocytes, neurons from the PFC showed more prototypical necrotic morphology in response to alcohol insults. In parallel, an increased protein level of CB1R was also found after 15 and 30 days alcohol exposure. Administration of specific inverse agonists of CB1R (AM251 and AM281), but not its agonists or CB2R modulators, significantly alleviated the RIP1/RIP3/MLKL-mediated neuronal necroptosis. Conclusion We reported the involvement of RIP1/RIP3/MLKL-mediated necroptosis in alcohol-induced PFC neurotoxicity, and identified CB1R as a critical regulator of neuronal necroptosis that enhanced our understanding of alcohol-induced neuropathology in the PFC.

Behavioral and stereological analysis of the prefrontal cortex of rats submitted to chronic alcohol intake

2019 ◽  
Vol 362 ◽  
pp. 21-27 ◽  
Author(s):  
Rafael Conte ◽  
Fernando Vagner Lobo Ladd ◽  
Aliny Antunes Barbosa Lobo Ladd ◽  
Amanda Lopez Moreira ◽  
Luciana Le Sueur-Maluf ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Alcohol Intake ◽  
Chronic Alcohol ◽  
Stereological Analysis

scholarly journals Chronic voluntary alcohol consumption causes persistent cognitive deficits and cortical cell loss in a rodent model

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Annai J. Charlton ◽  
Carlos May ◽  
Sophia J. Luikinga ◽  
Emma L. Burrows ◽  
Jee Hyun Kim ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Reaction Time ◽  
Alcohol Use ◽  
Cognitive Decline ◽  
Cell Density ◽  
Cognitive Deficits ◽  
Reaction Time Task ◽  
Serial Reaction Time Task ◽  
Chronic Alcohol ◽  
Serial Reaction

AbstractChronic alcohol use is associated with cognitive decline that impedes behavioral change during rehabilitation. Despite this, addiction therapy does not address cognitive deficits, and there is poor understanding regarding the mechanisms that underlie this decline. We established a rodent model of chronic voluntary alcohol use to measure ensuing cognitive effects and underlying pathology. Rats had intermittent access to alcohol or an isocaloric solution in their home cage under voluntary 2-bottle choice conditions. In Experiments 1 and 2 cognition was assessed using operant touchscreen chambers. We examined performance in a visual discrimination and reversal task (Experiment 1), and a 5-choice serial reaction time task (Experiment 2). For Experiment 3, rats were perfused immediately after cessation of alcohol access period, and volume, cell density and microglial populations were assessed in the prefrontal cortex and striatum. Volume was assessed using the Cavalieri probe, while cell and microglial counts were estimated using unbiased stereology with an optical fractionator. Alcohol-exposed and control rats showed comparable acquisition of pairwise discrimination; however, performance was impaired when contingencies were reversed indicating reduced behavioral flexibility. When tested in a 5-choice serial reaction time task alcohol-exposed rats showed increased compulsivity and increased attentional bias towards a reward associated cue. Consistent with these changes, we observed decreased cell density in the prefrontal cortex. These findings confirm a detrimental effect of chronic alcohol and establish a model of alcohol-induced cognitive decline following long-term voluntary intake that may be used for future intervention studies.

The effect of deer antler from East Kalimantan to increase trabecular bone density and calcium levels in serum on osteoporotic mice

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Retno Widyowati ◽  
Suciati Suciati ◽  
Dewi Melani Haryadi ◽  
Hsin-I Chang ◽  
IPG Ngurah Suryawan ◽  
...  
Keyword(s):  
Bone Density ◽  
Trabecular Bone ◽  
Aqueous Extract ◽  
Dependent Manner ◽  
Aqueous Extracts ◽  
Trabecular Bone Density ◽  
Male Mice ◽  
Deer Antler ◽  
East Kalimantan ◽  
Dose Dependent

Abstract Objectives Glucocorticoid-induced osteoporosis (dexamethasone) is a primary cause of secondary osteoporosis by the decreasing formation and increasing resorption activities. Previously, the in vitro study showed that 70% ethanol and aqueous extract of deer antler have increased alkaline phosphatase in osteoblast cell that known as marker of bone formation. The mind of this study is to analyze the effect of deer antlers in increasing the bone trabecular density of osteoporosis-induced male mice. Methods This study used a post-test control group design. A total of 54 healthy male mice were randomly divided to nine groups, i.e., healthy control, osteoporotic, positive control, 70% ethanol (4, 8, and 12 mg/kg BW), and aqueous extracts (4, 8, and 12 mg/kg BW) of deer antler groups. All of the interventions were given 1 mL of test sample for 4 weeks orally. The bone densities were determined using histomorphometry by Image J and Adobe Photoshop. The statistical data were performed using SPSS 23 and statistical significance was set at p<0.05. Results The results showed that alendronate group, 70% ethanol, and aqueous extract groups increased bone density and calcium levels in serum (p<0.05) compared to osteoporotic group in dose dependent manner. It indicated that 70% ethanol and aqueous extract of deer antler stimulating bone turnover and aqueous extract showed the highest. Conclusions Dexamethasone induction for 4 weeks caused osteoporotic mice and the administration of 70% ethanol and aqueous extracts of deer antler from East Kalimantan increased trabecular bone density and calcium levels in dose dependent manner.

scholarly journals The Influence of Diet and Sex on the Gut Microbiota of Lean and Obese JCR:LA-cp Rats

2021 ◽  
Vol 9 (5) ◽  
pp. 1037
Author(s):  
Craig Resch ◽  
Mihir Parikh ◽  
J. Alejandro Austria ◽  
Spencer D. Proctor ◽  
Thomas Netticadan ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Control Diet ◽  
Bacterial Species ◽  
Alpha Diversity ◽  
Short Chain Fatty Acids ◽  
Female Rats ◽  
Dependent Manner ◽  
Male And Female ◽  
Ground Flaxseed ◽  
The Impact

There is an increased interest in the gut microbiota as it relates to health and obesity. The impact of diet and sex on the gut microbiota in conjunction with obesity also demands extensive systemic investigation. Thus, the influence of sex, diet, and flaxseed supplementation on the gut microbiota was examined in the JCR:LA-cp rat model of genetic obesity. Male and female obese rats were randomized into four groups (n = 8) to receive, for 12 weeks, either (a) control diet (Con), (b) control diet supplemented with 10% ground flaxseed (CFlax), (c) a high-fat, high sucrose (HFHS) diet, or (d) HFHS supplemented with 10% ground flaxseed (HFlax). Male and female JCR:LA-cp lean rats served as genetic controls and received similar dietary interventions. Illumine MiSeq sequencing revealed a richer microbiota in rats fed control diets rather than HFHS diets. Obese female rats had lower alpha-diversity than lean female; however, both sexes of obese and lean JCR rats differed significantly in β-diversity, as their gut microbiota was composed of different abundances of bacterial types. The feeding of an HFHS diet affected the diversity by increasing the phylum Bacteroidetes and reducing bacterial species from phylum Firmicutes. Fecal short-chain fatty acids such as acetate, propionate, and butyrate-producing bacterial species were correspondingly impacted by the HFHS diet. Flax supplementation improved the gut microbiota by decreasing the abundance of Blautia and Eubacterium dolichum. Collectively, our data show that an HFHS diet results in gut microbiota dysbiosis in a sex-dependent manner. Flaxseed supplementation to the diet had a significant impact on gut microbiota diversity under both flax control and HFHS dietary conditions.

Propolis Prevents the Effects of Chronic Alcohol Intake on Ocular Tissues

2009 ◽  
Vol 42 (3) ◽  
pp. 147-151 ◽  
Author(s):  
Sinan Emre ◽  
Z&uuml;mr&uuml;t Y&inodot;lmaz ◽  
Feral &Ouml;zt&uuml;rk ◽  
M. Hanifi Emre
Keyword(s):  
Alcohol Intake ◽  
Chronic Alcohol ◽  
Ocular Tissues

Decrease in the Number of Muscarinic Receptors in Rat Pancreas after Chronic Alcohol Intake

1989 ◽  
Vol 64 (4) ◽  
pp. 356-359 ◽  
Author(s):  
Juha M. Grönroos ◽  
Timo Kaila ◽  
Heikki J. Aho ◽  
Timo J. Nevalainen
Keyword(s):  
Muscarinic Receptors ◽  
Alcohol Intake ◽  
Chronic Alcohol ◽  
Rat Pancreas

Chronic alcohol intake and carbachol-induced acute pancreatitis in the rat

1994 ◽  
Vol 46 (2) ◽  
pp. 163-167 ◽  
Author(s):  
Juha M. Grönroos ◽  
Jukka Laine ◽  
Timo Kaila ◽  
Timo J. Nevalainen
Keyword(s):  
Acute Pancreatitis ◽  
Alcohol Intake ◽  
Chronic Alcohol
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