scholarly journals Mirtazapine treatment in a young female mouse model of Rett syndrome identifies time windows for the rescue of early phenotypes during development

2021 ◽  
Author(s):  
Javier Flores Gutierrez ◽  
Giulia Natali ◽  
Jacopo Giorgi ◽  
Elvira De Leonibus ◽  
Enrico Tongiorgi
Keyword(s):  
Body Weight ◽  
Rett Syndrome ◽  
Adult Female ◽  
Primary Motor Cortex ◽  
Day Treatment ◽  
Histological Study ◽  
Time Windows ◽  
Neurodevelopmental Disorder ◽  
Knock Out ◽  
Positive Effects

Rett Syndrome (RTT) is a rare X-linked neurodevelopmental disorder, mainly caused by mutations in the MECP2 gene. Reduction in monoamine levels in RTT patients and mouse models suggested the possibility to rescue clinical phenotypes through antidepressants. Accordingly, we tested mirtazapine (MTZ), a noradrenergic and specific-serotonergic tetracyclic antidepressant (NaSSA). In previous studies, we showed high tolerability and significant positive effects of MTZ in male Mecp21m1.1Bird-knock-out mice, adult female Mecp2tm1.1Bird-heterozygous (Mecp2+/-) mice, and adult female RTT patients. However, it remained to explore MTZ efficacy in female Mecp2+/- mice at young ages. As RTT-like phenotypes in young Mecp2+/- mice have been less investigated, we carried out a behavioural characterization to analyze Mecp2+/- mice in "early adolescence" (6 weeks) and "late adolescence/young adulthood" (11 weeks) and identified several progressive phenotypes. Then, we evaluated the effects of either a 15- or a 30-day MTZ treatment on body weight and impaired motor behaviours in 11-week-old Mecp2+/- mice. Finally, since defective cortical development is a hallmark of RTT, we performed a histological study on the maturation of perineuronal nets (PNNs) and parvalbuminergic (PV) neurons in the primary motor cortex. The 30-day MTZ treatment was more effective than the shorter 15-day treatment, leading to the significant rescue of body weight, hindlimb clasping and motor learning in the accelerating rotarod test. Behavioral improvement was associated with normalized PV immunoreactivity levels and PNN thickness. These results support the use of MTZ as a new potential treatment for adolescent girls affected by RTT and suggest a possible mechanism of action.

scholarly journals Protective role of mirtazapine in adult female Mecp2+/− mice and patients with Rett syndrome

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Javier Flores Gutiérrez ◽  
Claudio De Felice ◽  
Giulia Natali ◽  
Silvia Leoncini ◽  
Cinzia Signorini ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Motor Learning ◽  
Disease Progression ◽  
Rett Syndrome ◽  
Adult Female ◽  
Primary Motor Cortex ◽  
Barrel Cortex ◽  
Motor Behavior ◽  
Clinical Severity ◽  
Long Term Treatment

Abstract Background Rett syndrome (RTT), an X-linked neurodevelopmental rare disease mainly caused by MECP2-gene mutations, is a prototypic intellectual disability disorder. Reversibility of RTT-like phenotypes in an adult mouse model lacking the Mecp2-gene has given hope of treating the disease at any age. However, adult RTT patients still urge for new treatments. Given the relationship between RTT and monoamine deficiency, we investigated mirtazapine (MTZ), a noradrenergic and specific-serotonergic antidepressant, as a potential treatment. Methods Adult heterozygous-Mecp2 (HET) female mice (6-months old) were treated for 30 days with 10 mg/kg MTZ and assessed for general health, motor skills, motor learning, and anxiety. Motor cortex, somatosensory cortex, and amygdala were analyzed for parvalbumin expression. Eighty RTT adult female patients harboring a pathogenic MECP2 mutation were randomly assigned to treatment to MTZ for insomnia and mood disorders (mean age = 23.1 ± 7.5 years, range = 16–47 years; mean MTZ-treatment duration = 1.64 ± 1.0 years, range = 0.08–5.0 years). Rett clinical severity scale (RCSS) and motor behavior assessment scale (MBAS) were retrospectively analyzed. Results In HET mice, MTZ preserved motor learning from deterioration and normalized parvalbumin levels in the primary motor cortex. Moreover, MTZ rescued the aberrant open-arm preference behavior observed in HET mice in the elevated plus-maze (EPM) and normalized parvalbumin expression in the barrel cortex. Since whisker clipping also abolished the EPM-related phenotype, we propose it is due to sensory hypersensitivity. In patients, MTZ slowed disease progression or induced significant improvements for 10/16 MBAS-items of the M1 social behavior area: 4/7 items of the M2 oro-facial/respiratory area and 8/14 items of the M3 motor/physical signs area. Conclusions This study provides the first evidence that long-term treatment of adult female heterozygous Mecp2tm1.1Bird mice and adult Rett patients with the antidepressant mirtazapine is well tolerated and that it protects from disease progression and improves motor, sensory, and behavioral symptoms.

Protective Effect of Silybum marianum and Nigella sativa Oil Extracts against Cisplatin Induced Nephrotoxicity in Mice

2018 ◽  
Vol 18 (2) ◽  
pp. 171-175
Author(s):  
Ashraf A. ◽  
Hassan F. ◽  
Batool S. ◽  
Nadeem M. ◽  
Irshad M. ◽  
...  
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Petroleum Ether ◽  
Nigella Sativa ◽  
Histological Study ◽  
The Body ◽  
Cellular Damage ◽  
Elevated Blood ◽  
Silybum Marianum ◽  
Elevated Blood Glucose

The objective of present study was to analyze and compare the nephroprotective effects of petroleum ether extracts of seeds of Nigella sativa and Silybum marianum in Swiss albino mice. Petroleum ether extracts of seeds of Nigella sativa and Silybum marianum were administered (200 mg kg–1) orally for 14 days following one dose of cisplatin injection (16 mg kg–1 i.p.) on 4th day. Cisplatin toxicity was identified in mice by loss of body weight, reduced triglycerides levels, elevated blood glucose, blood urea nitrogen and creatinine levels (P < 0.05). Silybum marianum and Nigella sativa significantly enhanced the body weight (9%) of diabetic rats. Silybum marianum had significantly reduced the elevated blood glucose (–106%), and BUN levels (–9%) as compared to the Nigella sativa administration. Silybum marianum extract also significantly elevated the levels of triglycerides (257%) which were much reduced after the cisplatin injection. Histological study showed that the cisplatin treated group demonstrated the necrosis signs in the glomerulus of Bowman’s capsule, hyalinization and severe cellular damage. The animals administered with extracts showed nearly normal kidney architecture, however, the kidney tissues of Silybum marianum-treated animals showed some improvement with slight signs of cellular damages.

scholarly journals Nucleotide Supplementation to Whole Milk Has Beneficial Effects on Post-Weaning Holstein Calf Performance

Animals ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 218
Author(s):  
Yousef Abbaslou ◽  
Davood Zahmatkesh ◽  
Ehsan Mahjoubi ◽  
Mehdi Hossein Yazdi ◽  
Hamed Beiranvand ◽  
...  
Keyword(s):  
Body Weight ◽  
Average Daily Gain ◽  
Free Access ◽  
Treatment Groups ◽  
Beneficial Effects ◽  
Positive Effects ◽  
Whole Milk ◽  
Calf Performance ◽  
Daily Gain ◽  
Fecal Score

The positive effects of nucleotide (NU) supplementation in milk replacer have been elucidated in infants and in dairy calves; however, NU addition to whole milk has not been evaluated previously. This study aimed to assess NU supplementation in the whole milk on calf growth and health. Thirty Holstein calves (body weight: 39.1 ± 1.0 kg; 3 d after birth) were randomly assigned to the following treatments: whole milk without any supplementation (NU0), whole milk + 0.5 g/d added a NU-containing supplement to whole milk (NUCS0.5), and whole milk + 1 g/d added a NU-containing supplement to whole milk (NUCS1). Calves were weaned at d 55 and stayed on study until d 75. Calves had free access to feed and water throughout the study. Dry matter intakes (DMI) were similar among treatments (p > 0.05) during the pre-weaning period; however, increasing NU resulted in a linear (p < 0.05) increase in DMI during the post weaning period (2158, 2432, and 2518 g/d for NU0, NUCS0.5, and NUCS1, respectively). Treatments did not affect body weight (BW) at the first and second month of study, but final BW linearly increased as NU was added (87.1, 90.6, and 95.4 kg for NU0, NUCS0.5, and NUCS1, respectively). Neither pre-weaning average daily gain nor post-weaning average daily gain was affected by treatments; accordingly, feed efficiency was similar among treatment groups. Days with loose fecal score were linearly decreased as NU was added to whole milk during the first month of life, while the fecal score did not differ among treatments until the end of the study. No difference was observed in the skeletal growth of calves in the current study. Therefore, it can be concluded that NU supplementation in the whole milk has some beneficial effects on calf performance in terms of final BW, post-weaning DMI, and less days with loose feces.

scholarly journals Time for a general approval of growth hormone treatment in adults with Prader–Willi syndrome

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Charlotte Höybye ◽  
◽  
Anthony J. Holland ◽  
Daniel J. Driscoll
Keyword(s):  
Growth Hormone ◽  
Body Composition ◽  
Transition Period ◽  
Neurodevelopmental Disorder ◽  
Hormone Treatment ◽  
Psychomotor Development ◽  
Prader Willi Syndrome ◽  
Gh Treatment ◽  
Beneficial Effects ◽  
Positive Effects

AbstractPrader-Willi syndrome (PWS) is a complex, multi-system, neurodevelopmental disorder characterised by neonatal muscular hypotonia, short stature, high risk of obesity, hypogonadism, intellectual disabilities, distinct behavioural/psychiatric problems and abnormal body composition with increased body fat and a deficit of lean body mass. Growth hormone (GH) deficiency and other hormone deficiencies are common due to hypothalamic dysfunction. In children with PWS GH treatment has been widely demonstrated to improve body composition, normalise height and improve psychomotor development. In adults with PWS, GH’s main effects are to maintain normal body structure and metabolism. The positive effects of GH treatment on body composition, physical fitness and beneficial effects on cardiovascular risk markers, behaviour and quality of life in adults with PWS are also well established from several studies. GH treatment is approved for treatment of children with PWS in many countries, but until recently not as a treatment in young adults in the transition period or for adults in general. In this commentary we want to draw attention to the uneven global use of GH treatment, specifically in adults with PWS, and advocate for GH treatment to be approved internationally, not just for children, but also for adults with PWS and based only on the diagnosis of genetically confirmed PWS.

Seasonal variations in wool growth and heat tolerance of sheep. I. Wool growth

1960 ◽  
Vol 11 (1) ◽  
pp. 75 ◽  
Author(s):  
M Wodzicka
Keyword(s):  
Body Weight ◽  
Day Treatment ◽  
The Other ◽  
Seasonal Rhythm ◽  
Group Iii ◽  
Wool Growth ◽  
Group I ◽  
The Mean ◽  
Group Ii ◽  
The Difference

The monthly wool growth of three groups of rams was studied at Beltsville, Maryland. Group I received natural daylight (at 38° 53' N.) and was shorn monthly. Group II had a 7:17 hours of daylight to hours of darkness rhythm and was shorn every 6 months, once in winter and once in summer. Group III received natural daylight and was likewise shorn every 6 months. The rams of all groups produced more wool in summer than in winter. This difference was significant (P<0.001). The mean body weight and food intake were both greater in the winter months, which indicated that the seasonal rhythm of wool growth was not a consequence of poorer feeding in winter. The rams which were shorn monthly (group I) grew considerably more wool than the other two groups, but the difference was not statistically significant. The short-day treatment of group II did not increase the annual wool production nor decrease the seasonal rhythm of wool growth. The balance of evidence from this and other experiments indicates that temperature rather than light controls the seasonal rhythm of wool growth.

Dissimilar Anxiety-like Behavior in Prepubertal and Young Adult Female Rats on Acute Exposure to Aluminium

2021 ◽  
Vol 22 ◽  
Author(s):  
Trina Sengupta ◽  
Sutirtha Ghosh ◽  
Archana Gaur T. ◽  
Prasunpriya Nayak
Keyword(s):  
Body Weight ◽  
Young Adult ◽  
Adult Female ◽  
Developmental Stages ◽  
Elevated Plus Maze ◽  
Age Groups ◽  
Female Rats ◽  
Acute Exposure ◽  
Adult Rats ◽  
Plus Maze

Background: Puberty is a developmental transition in which an estrogenic surge occurs, mediating the release of xenoestrogens, like aluminium. Aluminium’s effect on anxiety in rodents at the different developmental stages is inconsistent. Aims: This study aimed at investigating the effect of the metalloestrogenic property of aluminium on anxiety-like behavioral changes in prepubertal and young adult female rats. Objective: Considering this aim, our objective was to evaluate the anxiety-like behavior by the elevated plus maze in prepubertal and young adult female rats with or without acute exposure to aluminium. Methods: To address this property of aluminium, 5mg/Kg body weight (Al-5) and 10 mg/Kg body weight (Al-10) of aluminium was administered intraperitoneally to female rats at two developmental stages, prepubertal (PP; n = 8 for each dose) and young adult (YA; n = 6 for each dose) for two weeks. Post-treatment, three days behavioral assessment of the rats was done employing elevated plus maze. Results: Reduced escape latency was seen in Al-5, Al-10 pre-pubertal rats, and Al-5 young-adult rats on day 3. A significant reduction in open arm time was seen in the Al-5 young-adult rats. Aluminium treatment in the pre-pubertal rats reduced their head dipping and grooming. Reduced sniffing, head dipping, and stretch-attended posture in the treated young-adult female rats showed that they had impaired risk-taking tendency. Conclusion: Differential effect on the anxiety-like behavior in the pre-pubertal and young-adult female rats might be due to the metalloestrogenic property of aluminium, acting differently on the two age groups.

Body Shaping Through Aerobic Training in the Gym in Adult Women

2020 ◽  
Vol 65 (4) ◽  
pp. 97-107
Author(s):  
Alexandra Giurgiu ◽  
Iacob Hanțiu
Keyword(s):  
Body Weight ◽  
Physical Training ◽  
Aerobic Training ◽  
Ideal Body Weight ◽  
The Body ◽  
Adult Women ◽  
Hip Circumference ◽  
Positive Effects ◽  
Ideal Body ◽  
Training Exercises

ABSTRACT. Introduction. Regular physical activity has positive effects on human body composition, even if not combined with a diet. For many people this activity aims to reduce the amount of fat in some areas of the body and targets body shaping. Objectives. The main objective of this study was to learn about the effects of a 12-months regular participation in aerobic training exercises. Methods. This study was voluntarily attended by 89 women with an average age of 31.62, practicing aerobic exercises in gyms, three times a week for a period of 12 months. We carried out anthropometric measurements of subjects at the beginning and at end of the study, respectively, and data was statistically analysed using the SPSS 23.0 software. Results. Data collected was statistically processed, showing that participation in physical training led to reducing body weight by 4.81 kg, decrease of adipose tissue - between the two moments there was a difference of 5 % - fat mass decreased by 4.26 kg, and lean body mass by 0.55 kg. Significant decrease in chest, waist and hip circumference was also noticed. Conclusions. Regular participation in physical training programs involving aerobic exercise for 12 months has had the effect of reducing body weight and the amount of fat in some areas of the body, materialized by decreasing the value of the circumference of the chest, waist and hips, with the intention of reaching the ideal body weight and aiming for body shaping.

Effect of Yeast Type and Dose on Growth Performance and Nutrient Digestibility of Growing Rabbits Fed Maize or Barley

2021 ◽  
Author(s):  
Amr M.A. Elmasry ◽  
Luis A. Miranda ◽  
Germán Mendoza ◽  
Fernando X. Plata
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Body Weight ◽  
Growth Performance ◽  
Control Diet ◽  
Average Daily Gain ◽  
Nutrient Digestibility ◽  
Feed Conversion ◽  
Final Body Weight ◽  
Positive Effects ◽  
Yeast Concentration

Background: The effects of the probiotics vary with the doses and strains used for this reason, a study was conducted over 35 days to determine the effect of live yeast supplementation in the diet of growing rabbits on growth performance and apparent nutrient digestibility.Methods: A total of 60 New Zealand and California rabbits (5 weeks old, average body weight 0.881±0.015 kg) were housed in 30 cages. They were fed with a control diet based on alfalfa and maize or barley grains and supplemented with Procreatin®7 (Saccharomyces cerevisiae CNCM I 1077) or Biosaf® SC47 (Saccharomyces cerevisiae NCYC Sc47) at three doses, namely 0, 6.4, or 12.8 ×109 CFU per kg basal diet.Result: The higher yeast concentration had a positive effect (P less than 0.01) on final body weight (BW), average daily gain (ADG) and carcass weight (CW). However, there were no significant differences in dry matter intake. As a result of this, the feed conversion ratio (FCR) decreased (P less than 0.01). Significant increases (P less than 0.05) in nutrient digestibility (DM, OM, NDF and ADF) were observed with both grains. The use of yeast in maize and barley-based diets of rabbits has positive effects on growth performance and nutrient digestibility.

scholarly journals Effects of aqueous leaf extract of Corchorus olitorius on the testis and blood testosterone level of adult Wistar rats

2021 ◽  
Vol 10 (2) ◽  
pp. 024-030
Author(s):  
Godwin Chinedu Uloneme ◽  
Demian Nnabuihe Ezejindu ◽  
Darlington Cyprian Akukwu ◽  
Amadi Chibundu Chiekezie
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
Day Treatment ◽  
Control Group ◽  
Corchorus Olitorius ◽  
Group A ◽  
Normal Rat ◽  
Group B ◽  
Calcium Iron ◽  
Group D

Background: The extract of Corchorus olitorius has a reasonable content of vitamins A and C, calcium, iron and fibre, and therefore enjoys a universal application in the treatment of some disease conditions, even as the whole leaf is a very important component of food in so many cultures. Purpose: The study was designed to investigate the effect of Corchorus olitorius extracts on the testis of adult Wistar rats. Method: A total number of thirty two adult Wistar rats weighing between 180 and 200 grammes separated into four groups labeled A,B,C and D respectively were used for the study. Animals in group A which served as the control group were fed with the normal rat chow and water only. The group B rats were administered 100mg/kg body weight of aqueous extract of Corchorus olitorus; while those in group C were administered 500mg/kg body weight of the extract. The group D rats received 1000mg/kg body weight of the extract. For a period of four weeks, the different experimental animal groups received the respective aforementioned treatments once daily, around nine- o’clock in the morning through oral intubation. At the end of the 28 day treatment, the animals were sacrificed and the testes harvested for histological, investigation, and through cardiac puncture, blood samples for some hormonal studies was also collected and investigated using standard laboratory standards. Results: Observations made showed that the extract produced no histological distortions, degenerative or defective effects on the testicular tissues. The testosterone levels of group B, C, and D rats were observed to be significantly higher (P<0.005) than that of the group A (control group).ound: The extract of Corchorus olitorius has a reasonable content of vitamins A and C, calcium, iron and fibre, and therefore enjoys a universal application in the treatment of some disease conditions, even as the whole leaf is a very important component of food in so many cultures. Purpose: The study was designed to investigate the effect of Corchorus olitorius extracts on the testis of adult Wistar rats. Method: A total number of thirty two adult Wistar rats weighing between 180 and 200 grammes separated into four groups labeled A,B,C and D respectively were used for the study. Animals in group A which served as the control group were fed with the normal rat chow and water only. The group B rats were administered 100mg/kg body weight of aqueous extract of Corchorus olitorus; while those in group C were administered 500mg/kg body weight of the extract. The group D rats received 1000mg/kg body weight of the extract. For a period of four weeks, the different experimental animal groups received the respective aforementioned treatments once daily, around nine- o’clock in the morning through oral intubation. At the end of the 28 day treatment, the animals were sacrificed and the testes harvested for histological, investigation, and through cardiac puncture, blood samples for some hormonal studies was also collected and investigated using standard laboratory standards. Results: Observations made showed that the extract produced no histological distortions, degenerative or defective effects on the testicular tissues. The testosterone levels of group B, C, and D rats were observed to be significantly higher (P<0.005) than that of the group A (control group).

scholarly journals Glycosylation of CaV3.2 Channels Contributes to the Hyperalgesia in Peripheral Neuropathy of Type 1 Diabetes

2020 ◽  
Vol 14 ◽  
Author(s):  
Sonja Lj. Joksimovic ◽  
J. Grayson Evans ◽  
William E. McIntire ◽  
Peihan Orestes ◽  
Paula Q. Barrett ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Adult Female ◽  
Molecular Mechanisms ◽  
Sprague Dawley ◽  
Knock Out ◽  
Peripheral Diabetic Neuropathy ◽  
Novel Treatments

Our previous studies implicated glycosylation of the CaV3.2 isoform of T-type Ca2+ channels (T-channels) in the development of Type 2 painful peripheral diabetic neuropathy (PDN). Here we investigated biophysical mechanisms underlying the modulation of recombinant CaV3.2 channel by de-glycosylation enzymes such as neuraminidase (NEU) and PNGase-F (PNG), as well as their behavioral and biochemical effects in painful PDN Type 1. In our in vitro study we used whole-cell recordings of current-voltage relationships to confirm that CaV3.2 current densities were decreased ~2-fold after de-glycosylation. Furthermore, de-glycosylation induced a significant depolarizing shift in the steady-state relationships for activation and inactivation while producing little effects on the kinetics of current deactivation and recovery from inactivation. PDN was induced in vivo by injections of streptozotocin (STZ) in adult female C57Bl/6j wild type (WT) mice, adult female Sprague Dawley rats and CaV3.2 knock-out (KO mice). Either NEU or vehicle (saline) were locally injected into the right hind paws or intrathecally. We found that injections of NEU, but not vehicle, completely reversed thermal and mechanical hyperalgesia in diabetic WT rats and mice. In contrast, NEU did not alter baseline thermal and mechanical sensitivity in the CaV3.2 KO mice which also failed to develop painful PDN. Finally, we used biochemical methods with gel-shift analysis to directly demonstrate that N-terminal fragments of native CaV3.2 channels in the dorsal root ganglia (DRG) are glycosylated in both healthy and diabetic animals. Our results demonstrate that in sensory neurons glycosylation-induced alterations in CaV3.2 channels in vivo directly enhance diabetic hyperalgesia, and that glycosylation inhibitors can be used to ameliorate painful symptoms in Type 1 diabetes. We expect that our studies may lead to a better understanding of the molecular mechanisms underlying painful PDN in an effort to facilitate the discovery of novel treatments for this intractable disease.

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