scholarly journals Long-lasting beneficial effects of central serotonin receptor 7 stimulation in female mice modeling Rett syndrome

2015 ◽  
Vol 9 ◽  
Author(s):  
Bianca De Filippis ◽  
Valentina Chiodi ◽  
Walter Adriani ◽  
Enza Lacivita ◽  
Cinzia Mallozzi ◽  
...  
Keyword(s):  
Rett Syndrome ◽  
Serotonin Receptor ◽  
Female Mice ◽  
Beneficial Effects

Stimulation of the brain serotonin receptor 7 rescues mitochondrial dysfunction in female mice from two models of Rett syndrome

2017 ◽  
Vol 121 ◽  
pp. 79-88 ◽  
Author(s):  
Daniela Valenti ◽  
Lidia de Bari ◽  
Daniele Vigli ◽  
Enza Lacivita ◽  
Marcello Leopoldo ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Rett Syndrome ◽  
Serotonin Receptor ◽  
Brain Serotonin ◽  
Female Mice ◽  
The Brain ◽  
Stimulation Of

scholarly journals Cannabinoid and Cannabinoid-Related Receptors in the Myenteric Plexus of the Porcine Ileum

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 263
Author(s):  
Andrea Toschi ◽  
Giorgia Galiazzo ◽  
Andrea Piva ◽  
Claudio Tagliavia ◽  
Gemma Mazzuoli-Weber ◽  
...  
Keyword(s):  
Myenteric Plexus ◽  
Serotonin Receptor ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Visceral Pain ◽  
Wide Distribution ◽  
Nerve Fibers ◽  
Enteric Neurons ◽  
Beneficial Effects ◽  
Anatomical Basis

An important piece of evidence has shown that molecules acting on cannabinoid receptors influence gastrointestinal motility and induce beneficial effects on gastrointestinal inflammation and visceral pain. The aim of this investigation was to immunohistochemically localize the distribution of canonical cannabinoid receptor type 1 (CB1R) and type 2 (CB2R) and the cannabinoid-related receptors transient potential vanilloid receptor 1 (TRPV1), transient potential ankyrin receptor 1 (TRPA1), and serotonin receptor 5-HT1a (5-HT1aR) in the myenteric plexus (MP) of pig ileum. CB1R, TRPV1, TRPA1, and 5-HT1aR were expressed, with different intensities in the cytoplasm of MP neurons. For each receptor, the proportions of the immunoreactive neurons were evaluated using the anti-HuC/HuD antibody. These receptors were also localized on nerve fibers (CB1R, TRPA1), smooth muscle cells of tunica muscularis (CB1R, 5-HT1aR), and endothelial cells of blood vessels (TRPV1, TRPA1, 5-HT1aR). The nerve varicosities were also found to be immunoreactive for both TRPV1 and 5-HT1aR. No immunoreactivity was documented for CB2R. Cannabinoid and cannabinoid-related receptors herein investigated showed a wide distribution in the enteric neurons and nerve fibers of the pig MP. These results could provide an anatomical basis for additional research, supporting the therapeutic use of cannabinoid receptor agonists in relieving motility disorders in porcine enteropathies.

scholarly journals Overexpression of UBQLN1 reduces neuropathology in the P497S UBQLN2 mouse model of ALS/FTD

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Shaoteng Wang ◽  
Micaela Tatman ◽  
Mervyn J. Monteiro
Keyword(s):  
Mouse Model ◽  
Neuronal Loss ◽  
Body Weight Loss ◽  
Missense Mutations ◽  
Homologous Proteins ◽  
Female Mice ◽  
Beneficial Effects ◽  
Therapeutic Benefits ◽  
Gender Specific ◽  
Lateral Sclerosis

Abstract Missense mutations in UBQLN2 cause X-linked dominant inheritance of amyotrophic lateral sclerosis with frontotemporal dementia (ALS/FTD). UBQLN2 belongs to a family of four highly homologous proteins expressed in humans that play diverse roles in maintaining proteostasis, but whether one isoform can substitute for another is not known. Here, we tested whether overexpression of UBQLN1 can alleviate disease in the P497S UBQLN2 mouse model of ALS/FTD by crossing transgenic (Tg) mouse lines expressing the two proteins and characterizing the resulting genotypes using a battery of pathologic and behavioral tests. The pathologic findings revealed UBQLN1 overexpression dramatically reduced the burden of UBQLN2 inclusions, neuronal loss and disturbances in proteostasis in double Tg mice compared to single P497S Tg mice. The beneficial effects of UBQLN1 overexpression were primarily confirmed by behavioral improvements seen in rotarod performance and grip strength in male, but not female mice. Paradoxically, although UBQLN1 overexpression reduced pathologic signatures of disease in P497S Tg mice, female mice had larger percentage of body weight loss than males, and this correlated with a corresponding lack of behavioral improvements in the females. These findings lead us to speculate that methods to upregulate UBQLN1 expression may reduce pathogenicity caused by UBQLN2 mutations, but may also lead to gender-specific outcomes that will have to be carefully weighed with the therapeutic benefits of UBQLN1 upregulation.

scholarly journals Deficient Purposeful Use of Forepaws in Female Mice Modelling Rett Syndrome

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Bianca De Filippis ◽  
Mattia Musto ◽  
Luisa Altabella ◽  
Emilia Romano ◽  
Rossella Canese ◽  
...  
Keyword(s):  
Rett Syndrome ◽  
Motor Coordination ◽  
Neurodevelopmental Disorder ◽  
Fine Motor ◽  
Resonance Spectroscopy ◽  
Fine Motor Skill ◽  
Female Mice ◽  
Fine Grain ◽  
Motor Abnormalities

Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioural and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2) cause more than 95% of classic cases. Motor abnormalities represent a significant part of the spectrum of RTT symptoms. In the present study we investigated motor coordination and fine motor skill domains in MeCP2-308 female mice, a validated RTT model. This was complemented by thein vivomagnetic resonance spectroscopy (MRS) analysis of metabolic profile in behaviourally relevant brain areas. MeCP2-308 heterozygous female mice (Het, 10-12 months of age) were impaired in tasks validated for the assessment of purposeful and coordinated forepaw use (Morag testandCapellini handling task). A fine-grain analysis of spontaneous behaviour in the home-cage also revealed an abnormal handling pattern when interacting with the nesting material, reduced motivation to explore the environment, and increased time devoted to feeding in Het mice. The brain MRS evaluation highlighted decreased levels of bioenergetic metabolites in the striatal area in Het mice compared to controls. Present results confirm behavioural and brain alterations previously reported in MeCP2-308 males and identify novel endpoints on which the efficacy of innovative therapeutic strategies for RTT may be tested.

scholarly journals Neuroprotective Effects of a Combined Therapy With Memantine, Donepezil and Vitamin D in Ovariectomized Female Mice Subjected to Dementia Model

2021 ◽  
Author(s):  
Ana Daniela Coutinho Vieira ◽  
Eduarda Behenck Medeiros ◽  
Gabriel Casagrande Zabot ◽  
Nathalia de Souza Pereira ◽  
Natália Baltazar do Nascimento ◽  
...  
Keyword(s):  
Vitamin D ◽  
Combined Therapy ◽  
Neuroprotective Effects ◽  
Female Mice ◽  
Beneficial Effects ◽  
Gfap Immunoreactivity ◽  
Short And Long Term ◽  
Triple Treatment ◽  
Inflammation Parameters

Abstract The postmenopausal period is characterized by a decrease in the hormonal supply which is associated with Alzheimer's Disease (AD). Vitamin D is neuroprotective and can be used in combination with pre-existing medications to improve its effects. The objective was to evaluate the effect of vitamin D associated with memantine and donepezil in female mice submitted to ovariectomy (OVX) for 5 months and subjected to an AD-induced dementia model. Animals were divided into 5 groups who received 17 days of treatment and were subjected to behavioral tests. The animals underwent euthanasia at 18th day. OVX groups exhibit reduced levels of E2 and triple treatment group had high levels of vitamin D. The induction of dementia with OVX induced short- and long-term spatial and habituation memories damage. Also, induced reduction of BDNF and IL-4 levels in hippocampus, and increasing levels of TNFα in hippocampus and of IL-1β in hippocampus and frontal cortex of animals, as well as a significant increase on GFAP immunoreactivity. Triple-association treatment reversed the effects of long-term spatial and habituation memories damage, as well as reversed changes in TNFα, IL-1β, IL-4 and GFAP immunoreactivity levels in hippocampus of treated animals. Therapeutic association has beneficial effects on memory and inflammation parameters in female mice subjected to OVX and the AD animal model of dementia.

Beneficial Effects of Lithium on Severe Irritability in a Patient with Rett Syndrome

2016 ◽  
Vol 26 (10) ◽  
pp. 949-949
Author(s):  
Duygu Kinay ◽  
Ilyas Kaya ◽  
Ahmet Zihni Soyata ◽  
Ayse Kilincaslan
Keyword(s):  
Rett Syndrome ◽  
Beneficial Effects

scholarly journals Lactation improves pancreatic β cell mass and function through serotonin production

2020 ◽  
Vol 12 (541) ◽  
pp. eaay0455
Author(s):  
Joon Ho Moon ◽  
Hyeongseok Kim ◽  
Hyunki Kim ◽  
Jungsun Park ◽  
Wonsuk Choi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Proliferation ◽  
Glucose Tolerance ◽  
Serotonin Receptor ◽  
Cell Function ◽  
Cell Mass ◽  
Β Cells ◽  
Β Cell ◽  
Beneficial Effects

Pregnancy imposes a substantial metabolic burden on women through weight gain and insulin resistance. Lactation reduces the risk of maternal postpartum diabetes, but the mechanisms underlying this benefit are unknown. Here, we identified long-term beneficial effects of lactation on β cell function, which last for years after the cessation of lactation. We analyzed metabolic phenotypes including β cell characteristics in lactating and non-lactating humans and mice. Lactating and non-lactating women showed comparable glucose tolerance at 2 months after delivery, but after a mean of 3.6 years, glucose tolerance in lactated women had improved compared to non-lactated women. In humans, the disposition index, a measure of insulin secretory function of β cells considering the degree of insulin sensitivity, was higher in lactated women at 3.6 years after delivery. In mice, lactation improved glucose tolerance and increased β cell mass at 3 weeks after delivery. Amelioration of glucose tolerance and insulin secretion were maintained up to 4 months after delivery in lactated mice. During lactation, prolactin induced serotonin production in β cells. Secreted serotonin stimulated β cell proliferation through serotonin receptor 2B in an autocrine and paracrine manner. In addition, intracellular serotonin acted as an antioxidant to mitigate oxidative stress and improved β cell survival. Together, our results suggest that serotonin mediates the long-term beneficial effects of lactation on female metabolic health by increasing β cell proliferation and reducing oxidative stress in β cells.

Modulation of Rho GTPases rescues brain mitochondrial dysfunction, cognitive deficits and aberrant synaptic plasticity in female mice modeling Rett syndrome

2015 ◽  
Vol 25 (6) ◽  
pp. 889-901 ◽  
Author(s):  
Bianca De Filippis ◽  
Daniela Valenti ◽  
Valentina Chiodi ◽  
Antonella Ferrante ◽  
Lidia de Bari ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Mitochondrial Dysfunction ◽  
Rett Syndrome ◽  
Cognitive Deficits ◽  
Rho Gtpases ◽  
Female Mice

scholarly journals Stimulation of the Serotonin Receptor 7 Restores Brain Histone H3 Acetylation and MeCP2 Corepressor Protein Levels in a Female Mouse Model of Rett Syndrome

2021 ◽  
Vol 80 (3) ◽  
pp. 265-273
Author(s):  
Giorgia Napoletani ◽  
Daniele Vigli ◽  
Livia Cosentino ◽  
Maddalena Grieco ◽  
Maria Cristina Talamo ◽  
...  
Keyword(s):  
Mouse Model ◽  
Rett Syndrome ◽  
Serotonin Receptor ◽  
Histone H3 ◽  
Protein Levels ◽  
Mouse Cortex ◽  
Histone H3 Acetylation ◽  
H3 Acetylation ◽  
The Relationship ◽  
Stimulation Of

Abstract Rett syndrome (RTT) is a rare neurological disorder caused by mutations in the X-linked MECP2 gene, characterized by severe behavioral and physiological impairments for which no cure is available. The stimulation of serotonin receptor 7 (5-HT7R) with its selective agonist LP-211 (0.25 mg/kg/day for 7 days) was proved to rescue neurobehavioral alterations in a mouse model of RTT. In the present study, we aimed at gaining insight into the mechanisms underpinning the efficacy of 5-HT7R pharmacological stimulation by investigating its epigenetic outcomes in the brain of RTT female mice bearing a truncating MeCP2 mutation. Treatment with LP-211 normalized the reduced histone H3 acetylation and HDAC3/NCoR levels, and increased HDAC1/Sin3a expression in RTT mouse cortex. Repeated 5-HT7R stimulation also appeared to strengthen the association between NCoR and MeCP2 in the same brain region. A different profile was found in RTT hippocampus, where LP-211 rescued H3 hyperacetylation and increased HDAC3 levels. Overall, the present data highlight a new scenario on the relationship between histone acetylation and serotoninergic pathways. 5-HT7R is confirmed as a pivotal therapeutic target for the recovery of neuronal function supporting the translational value of this promising pharmacological approach for RTT.

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