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Pharmacology, Biochemistry, and Behavior Dec 2019Ample evidences have demonstrated the beneficial effects of physical exercise on cognitive functions such as learning and memory. It is well established that female sex...
Ample evidences have demonstrated the beneficial effects of physical exercise on cognitive functions such as learning and memory. It is well established that female sex hormones have an important role in regulating learning and memory. This study was designed to investigate the effects of voluntary exercise and estrogen replacement on learning and memory deficits and reduction in hippocampal brain derived neurotrophic factor (BDNF) levels induced by ovariectomy. Ovariectomized rats were given daily vehicle or 17 β-estradiol (20 μg/kg) and allowed to freely exercise in a running wheel over the course of 2 weeks. After this period, they were trained and tested on a water-maze spatial task for 5 consecutive days, followed by a probe test one day later. At the end of the behavioral tests, all animals were decapitated and their hippocampal levels of BDNF were measured. Ovariectomy impaired spatial learning and memory and reduced hippocampal BDNF levels. Exercise significantly improved performance during both training and the retention of the water-maze task and increased hippocampal BDNF. Exercise, 17 β-estradiol and their combination recovered the impairing effects of ovariectomy on learning and memory performance. The combined treatment did not produce stronger effect than either exercise or 17 β-estradiol alone. Our findings provide an important evidence about positive influences of regular exercise and estrogen treatment against cognitive and BDNF deficits induced in ovariectomized rats, an experimental model of menopause.
Topics: Animals; Brain-Derived Neurotrophic Factor; Cognitive Dysfunction; Estradiol; Estrogens; Exercise Therapy; Female; Hippocampus; Memory; Memory Disorders; Menopause; Models, Animal; Ovariectomy; Physical Conditioning, Animal; Rats; Rats, Wistar; Spatial Learning
PubMed: 31697961
DOI: 10.1016/j.pbb.2019.172819 -
Journal of Interventional Medicine Feb 2023This study investigated the anatomical and histological characteristics of the rat Eustachian tube (E-tube) and the feasibility of Eustachian tubography in a rat model.
PURPOSE
This study investigated the anatomical and histological characteristics of the rat Eustachian tube (E-tube) and the feasibility of Eustachian tubography in a rat model.
MATERIALS AND METHODS
Fifteen male Wistar rats were used in this study, and the bilateral E-tubes of each rat were examined. Ten E-tubes were used for anatomical studies, another ten for histological analysis, and the other ten for Eustachian tubography. Five rats were euthanized and decapitated, and ten E-tubes were dissected to describe the anatomy of the E-tube. Ten E-tube specimens obtained from five other rats were sectioned to investigate E-tube histology. Eustachian tubography was performed on the bilateral E-tubes of the other five rats using the -tympanic approach.
RESULTS
The rat E-tubes consisted of bony and membranous parts. Cartilage and bone tissue covered only the bony part. The E-tubes' mean diameter and overall length were 2.97 mm and 4.96 mm, respectively. The tympanic orifices' mean diameter was 1.21 mm. The epithelium of E-tubes was mainly composed of pseudostratified ciliated and goblet cells. Eustachian tubography was successfully performed on both sides of the E-tube for each rat. The technical success rate was 100%, the average running time was 4.9 min, and no procedure-related complications occurred. On tubography images, the E-tube, tympanic cavity, and nasopharynx could be identified because of the visualization of bony landmarks.
CONCLUSION
In this study, we described the anatomical and histological features of rat E-tubes. With the aid of these findings, E-tube angiography was successfully performed using a transtympanic approach. These results will facilitate further investigation of E-tube dysfunction.
PubMed: 37180372
DOI: 10.1016/j.jimed.2022.12.002 -
The American Journal of Forensic... Sep 2019Separation of the head from the body can occur for a variety of reasons and in various locations across the neck. This study presents a review of the literature to... (Review)
Review
Separation of the head from the body can occur for a variety of reasons and in various locations across the neck. This study presents a review of the literature to identify the patterns of decapitations in forensic cases in relation to manner of death, age, and anatomical location (n = 88). The most common manner of death was suicide, followed by homicide and then accident. Ages ranged from 32 weeks prenatal to 85 years. Decapitation is reported at higher rates for individuals between 19 and 65. The majority of decapitations occurred at the midneck (second to fifth cervical vertebrae), followed by the upper neck and then the lower neck. This pattern holds true for all manners of death; however, in homicides, the percentage occurring at the midneck decreases. The findings of this study indicate some patterns in terms of manner of death, age, and location of decapitation, which could aid the medicolegal community in interpreting neck trauma. A case study is also briefly presented to illustrate findings.
Topics: Accidents; Age Distribution; Cervical Vertebrae; Decapitation; Female; Forensic Pathology; Homicide; Humans; Pregnancy; Prenatal Injuries; Suicide; Vacuum Extraction, Obstetrical
PubMed: 31205058
DOI: 10.1097/PAF.0000000000000490 -
The Journal of Pharmacology and... Jun 20213,4-Methylenedioxy--methylcathinone (methylone) is a new psychoactive substance with stimulant properties and potential for abuse. Despite its popularity, limited...
3,4-Methylenedioxy--methylcathinone (methylone) is a new psychoactive substance with stimulant properties and potential for abuse. Despite its popularity, limited studies have examined relationships between brain concentrations of methylone, its metabolites, and pharmacodynamic effects. The goal of the present study was 2-fold: 1) to determine pharmacokinetics of methylone and its major metabolites-4-hydroxy-3-methoxy-methylcathinone (HMMC), 3,4-dihydroxy-methylcathinone (HHMC), and 3,4-methylenedioxycathinone (MDC)-in rat brain and plasma and 2) to relate brain pharmacokinetic parameters to pharmacodynamic effects including locomotor behavior and postmortem neurochemistry. Male Sprague-Dawley rats received subcutaneous methylone (6, 12, or 24 mg/kg) or saline vehicle ( = 16/dose), and subgroups were decapitated after 40 or 120 minutes. Plasma and prefrontal cortex were analyzed for concentrations of methylone and its metabolites by liquid chromatography-tandem mass spectrometry. Frontal cortex and dorsal striatum were analyzed for dopamine, 5-HT, and their metabolites by high-performance liquid chromatography-electrochemical detection. Brain and plasma concentrations of methylone and its metabolites rose with increasing methylone dose, but brain methylone and MDC concentrations were greater than dose-proportional. Brain-to-plasma ratios for methylone and MDC were ≥ 3 (range 3-12), whereas those for HHMC and HMMC were ≤ 0.2 (range 0.01-0.2). Locomotor activity score was positively correlated with brain methylone and MDC, whereas cortical 5-HT was negatively correlated with these analytes at 120 minutes. Our findings show that brain concentrations of methylone and MDC display nonlinear accumulation. Behavioral and neurochemical effects of systemically administered methylone are related to brain concentrations of methylone and MDC but not its hydroxylated metabolites, which do not effectively penetrate into the brain. SIGNIFICANCE STATEMENT: Behavioral and neurochemical effects of methylone are related to brain concentrations of methylone and its metabolite MDC but not its hydroxylated metabolites, 4-hydroxy-3-methoxy-methylcathinone and 3,4-dihydroxy-methylcathinone, which do not effectively penetrate into the brain. Methylone and MDC display nonlinear accumulation in the brain, which could cause untoward effects on serotonin neurons in vulnerable brain regions, including the frontal cortex.
Topics: Animals; Brain; Dopamine; Rats; Serotonin
PubMed: 33785525
DOI: 10.1124/jpet.121.000531 -
Drug and Chemical Toxicology Nov 2022This study aimed to reveal the possible protective effect of dapagliflozin (DAPA) against acute kidney damage due to cyclosporine A (CsA). Thirty-two mice with an...
This study aimed to reveal the possible protective effect of dapagliflozin (DAPA) against acute kidney damage due to cyclosporine A (CsA). Thirty-two mice with an eight-week-old Balb\c albino strain were divided into four groups: control group, CsA group, DAPA group, and CsA + DAPA group. On day 9 of treatment, the animals were decapitated, and bilateral nephrectomy was performed. Oxidative stress and apoptosis were evaluated with caspase-3 activity, total oxidant status (TOS), total antioxidant status (TAS), malondialdehyde (MDA), myeloperoxidase (MPO), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in the right kidney resection material. The left kidney resection material was evaluated histopathologically. CsA increased caspase-3 activity, Bax, TOS, MDA, TAS, and MPO levels, and the administration of DAPA with CsA significantly reduced this increase in levels ( < 0.001, < 0.001, < 0.001, < 0.001, < 0.001, and < 0.001, respectively). CsA decreased Bcl-2 levels, and administration of CsA + DAPA significantly increased Bcl-2 levels compared with only CsA administration ( < 0.001). Additionally, administration of DAPA significantly reduced the histopathological findings (parenchymal inflammation, hyaline cast formation, vacuolization, and lysis of renal tubular cells) caused by CsA. DAPA reduces oxidative stress, apoptosis, and histopathological damage caused by CsA in renal tissue.
Topics: Animals; Mice; Antioxidants; bcl-2-Associated X Protein; Caspase 3; Cyclosporine; Immunosuppressive Agents; Kidney; Kidney Diseases; Malondialdehyde; Oxidants; Peroxidase
PubMed: 34565275
DOI: 10.1080/01480545.2021.1979996 -
Molecular Neurobiology Dec 2023Depressive disorder is a severe and complex mental illness. There are a few anti-depressive medications that can reduce depressive symptoms, but with adverse or side...
Depressive disorder is a severe and complex mental illness. There are a few anti-depressive medications that can reduce depressive symptoms, but with adverse or side effects. GaoYou-13 (GY-13), commonly known as Areca Thirteen Pill, is a traditional medicine for depression treatment with significant clinical impact. However, the molecular mechanism of GY-13 has not been fully elucidated. This study aimed to explore and explain the action and mechanism of GY-13 in treatment for depression. SD male rats were stimulated differently daily for 42 days to construct a depression rat model and divided into six groups: the control, CUMS model, GY-13L, GY-13 M, GY-13H, and FLUO. The body weight of was measured on day 7, 14, 21, 28, 35, and 42 or different days, and the behavioral tests (Open-field test, Sucrose preference test, Morris water maze) were made alongside. After the rats were decapitated, the rat brains were stained with Nissl or H&E dyes. The serums of TNF-α and IL-1β were tested. The protein of p-IKKα, p-IкBα, and p-NFкBp65 was traced. Then nano-LC-MS/MS analysis was made to detect the mechanism of GY-13. The active ingredients, drug targets, and key pathways of GY-13 in treating depression were analyzed through network pharmacology and molecular docking. With immunohistochemistry, quantitative RT-PCR, and western-blot techniques, the therapeutic mechanism of GY-13 was traced and analyzed. This study revealed that GY-13 significantly enhances autonomous and exploratory behavior, sucrose consumption, learning and memory ability, and hippocampal neuronal degeneration, which inhibits inflammation. In addition, omics analysis showed several proteins were altered in the hippocampus of rats following CUMS and GY-13 treatment. Bioinformatics analysis and network pharmacology revealed the antidepressant effects of GY-13 are related to the chemokine/chemokine receptor axis. Immunohistochemistry, western blotting and RT-PCR assay further support the findings of omics analysis. We highlighted the importance of the chemokine/chemokine receptor axis in the treatment of depression, as well as showed GY-13 can be used as a novel targeted therapy for depression treatment.
PubMed: 38110645
DOI: 10.1007/s12035-023-03855-1 -
PloS One 2021The rotenone-induced animal model of Parkinson's disease (PD) has been used to investigate the pathogenesis of PD. Oxidative stress is one of the main contributors of...
The rotenone-induced animal model of Parkinson's disease (PD) has been used to investigate the pathogenesis of PD. Oxidative stress is one of the main contributors of neurodegeneration in PD. Flavonoids have the potential to modulate neuronal function and combat various neurodegenerative diseases. The pre- and post-supplementation of quercetin (50 mg/kg, p.o) was done in rats injected with rotenone (1.5 mg/kg, s.c). After the treatment, behavioral activities were monitored for motor activity, depression-like behavior, and cognitive changes. Rats were decapitated after behavioral analysis and the brain samples were dissected out for neurochemical and biochemical estimation. Results showed that supplementation of quercetin significantly (p<0.01) restored rotenone-induced motor and non-motor deficits (depression and cognitive impairments), enhanced antioxidant enzyme activities (p<0.01), and attenuated neurotransmitter alterations (p<0.01). It is suggested that quercetin supplementation improves neurotransmitter levels by mitigating oxidative stress via increasing antioxidant enzyme activity and hence improves motor activity, cognitive functions, and reduces depressive behavior. The results of the present study showed that quercetin pre-supplementation produced more significant results as compared to post-supplementation. These findings show that quercetin can be a potential therapeutic agent to reduce the risk and progression of PD.
Topics: Animals; Antioxidants; Behavior, Animal; Cognition; Cognitive Dysfunction; Depression; Disease Models, Animal; Male; Motor Activity; Neuroprotective Agents; Neurotransmitter Agents; Oxidative Stress; Parkinson Disease, Secondary; Quercetin; Rats; Rats, Wistar; Rotenone; Signal Transduction; Treatment Outcome
PubMed: 34767546
DOI: 10.1371/journal.pone.0258928 -
PloS One 2021We aimed to describe the epidemiology of statue attacks along with statue representativeness relative to modern day demographics in one case study country: New Zealand.
OBJECTIVES
We aimed to describe the epidemiology of statue attacks along with statue representativeness relative to modern day demographics in one case study country: New Zealand.
METHODS
We performed Internet searches for the existence of outdoor statues of named individuals and historical attacks in New Zealand (NZ), combined a national survey with field visits to all identified statues to examine for injuries and repairs.
RESULTS
Of the 123 statues identified, nearly a quarter (n = 28, 23%) had been attacked at least once (total of 45 separate attack events), with the number of attacks increasing from the 1990s. Attacks involved paint/graffiti (14% of all statues at least once), nose removal/damage (7%), decapitation (5%), and total destruction (2%). The risk of attack was relatively higher for statues of royalty (50%), military personnel (33%), explorers (29%), and politicians (25%), compared to other reasons for fame (eg, 0% for sports players). Statue subjects involved in colonialism or direct harm to Māori (Indigenous population), had 6.61 (95%CI: 2.30 to 19.9) greater odds (adjusted odds ratio) of being attacked than other subjects. Most of the statue subjects were of men (87%) and Europeans (93%). Other ethnicities were 6% Māori (comprising 15% of the population) and 1% each for Asian and Pacific peoples, who comprise 12% and 7% of the population respectively.
CONCLUSIONS
This national survey found an association between statue attacks and the role of statue subjects in colonialism or direct harm to the Indigenous population. Furthermore, the demography of the statue subjects may represent historical and current social power relationships-with under-representation of women and non-European ethnic groups.
Topics: Crime; Humans; New Zealand
PubMed: 34081698
DOI: 10.1371/journal.pone.0252567 -
BMC Neuroscience Feb 2022The TRH/TRH-R1 receptor signaling pathway within the neurons of the dorsal vagal complex is an important mediator of the brain-gut axis. Mental health and protection...
BACKGROUND
The TRH/TRH-R1 receptor signaling pathway within the neurons of the dorsal vagal complex is an important mediator of the brain-gut axis. Mental health and protection from a variety of neuropathologies, such as autism, Attention Deficit Hyperactivity Disorder, Alzheimer's and Parkinson's disease, major depression, migraine and epilepsy are influenced by the gut microbiome and is mediated by the vagus nerve. The antibiotic rifaximin (RF) does not cross the gut-blood barrier. It changes the composition of the gut microbiome resulting in therapeutic benefits for traveler's diarrhea, hepatic encephalopathy, and prostatitis. TRH and TRH-like peptides, with the structure pGlu-X-Pro-NH, where "X" can be any amino acid residue, have reproduction-enhancing, caloric-restriction-like, anti-aging, pancreatic-β cell-, cardiovascular-, and neuroprotective effects. TRH and TRH-like peptides occur not only throughout the CNS but also in peripheral tissues. To elucidate the involvement of TRH-like peptides in brain-gut-reproductive system interactions 16 male Sprague-Dawley rats, 203 ± 6 g, were divided into 4 groups (n = 4/group): the control (CON) group remained on ad libitum Purina rodent chow and water for 10 days until decapitation, acute (AC) group receiving 150 mg RF/kg powdered rodent chow for 24 h providing 150 mg RF/kg body weight for 200 g rats, chronic (CHR) animals receiving RF for 10 days; withdrawal (WD) rats receiving RF for 8 days and then normal chow for 2 days.
RESULTS
Significant changes in the levels of TRH and TRH-like peptides occurred throughout the brain and peripheral tissues in response to RF. The number of significant changes in TRH and TRH-like peptide levels in brain resulting from RF treatment, in descending order were: medulla (16), piriform cortex (8), nucleus accumbens (7), frontal cortex (5), striatum (3), amygdala (3), entorhinal cortex (3), anterior (2), and posterior cingulate (2), hippocampus (1), hypothalamus (0) and cerebellum (0). The corresponding ranking for peripheral tissues were: prostate (6), adrenals (4), pancreas (3), liver (2), testis (1), heart (0).
CONCLUSIONS
The sensitivity of TRH and TRH-like peptide expression to RF treatment, particularly in the medulla oblongata and prostate, is consistent with the participation of these peptides in the therapeutic effects of RF.
Topics: Animals; Brain; Diarrhea; Female; Male; Peptides; Rats; Rats, Sprague-Dawley; Rifaximin; Thyrotropin-Releasing Hormone; Travel
PubMed: 35189807
DOI: 10.1186/s12868-022-00694-z -
Anaesthesia Sep 2020Historically, there has been a tendency to think that there are two types of death: circulatory and neurological. Holding onto this tendency is making it harder to... (Review)
Review
Historically, there has been a tendency to think that there are two types of death: circulatory and neurological. Holding onto this tendency is making it harder to navigate emerging resuscitative technologies, such as extracorporeal membrane oxygenation and the recent well-publicised experiment that demonstrated the possibility of restoring cellular function to some brain neurons 4 h after normothermic circulatory arrest (decapitation) in pigs. Attempts have been made to respond to these difficulties by proposing a unified brain-based criterion for human death, which we call 'permanent brain arrest'. The clinical characteristics of permanent brain arrest are the permanent loss of capacity for consciousness and permanent loss of all brainstem functions, including the capacity to breathe. These losses could arise from a primary brain injury or as a result of systemic circulatory arrest. We argue that permanent brain arrest is the true and sole criterion for the death of human beings and show that this is already implicit in the circulatory-respiratory criterion itself. We argue that accepting the concept of permanent cessation of brain function in patients with systemic permanent circulatory arrest will help us better navigate the medical advances and new technologies of the future whilst continuing to provide sound medical criteria for the determination of death.
Topics: Brain Death; Heart Arrest; Humans
PubMed: 32430978
DOI: 10.1111/anae.15050