Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in methyl-CpG-binding protein-2 (), a transcriptional regulator of many genes, including brain-derived neurotrophic factor (). BDNF levels are reduced in RTT autopsy brains and in multiple brain areas of -deficient mice. Furthermore, experimental interventions that increase BDNF levels improve RTT-like phenotypes in mutant mice. Here, we characterized the actions of a small-molecule ligand of the BDNF receptor TrkB in hippocampal function in mutant mice. Systemic treatment of female heterozygous (HET) mice with LM22A-4 for 4 weeks improved hippocampal-dependent object location memory and restored hippocampal long-term potentiation (LTP). Mechanistically, LM22A-4 acts to dampen hyperactive hippocampal network activity, reduce the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs), and reduce the frequency of spontaneous tetrodotoxin-resistant Ca signals in mutant hippocampal neurons, making them comparable to those features observed in wild-type neurons. Together, these observations indicate that LM22A-4 is a promising therapeutic candidate for the treatment of hippocampal dysfunction in RTT.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536912 | PMC |
| http://dx.doi.org/10.1242/dmm.029959 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The role of spatial location in irrelevant speech revisited: A preregistered replication study.
J Exp Psychol Learn Mem Cogn
December 2024
Technical University of Darmstadt, Institute of Psychology.
The goal of the present investigation was to perform a registered replication of Jones and Macken's (1995b) study, which showed that the segregation of a sequence of sounds to distinct locations reduced the disruptive effect on serial recall. Thereby, it postulated an intriguing connection between auditory stream segregation and the cognitive mechanisms underlying the irrelevant speech effect. Specifically, it was found that a sequence of changing utterances was less disruptive in stereophonic presentation, allowing each auditory object (letters) to be allocated to a unique location (right ear, left ear, center), compared to when the same sounds were played monophonically.
View Article and Find Full Text PDFForeign body ingestion in children attending Rapareen Teaching Hospital: a single-centre experience.
Prz Gastroenterol
August 2023
Pediatric Department, Hawler Medical University, Erbil, Iraq.
Introduction: Ingestion of foreign bodies is a significant problem among children, which necessitates early intervention and may lead to serious morbidity and even mortality.
Aim: To estimate the pattern of foreign body ingestion among children and identify the role of management and its outcomes in relation to the type and site of foreign bodies.
Material And Methods: Our study was carried out on patients who attended the Emergency Department of the Rapareen Teaching Hospital for Paediatrics in Erbil city and were referred to the Paediatric Gastroenterology Unit during between March 2019 and January 2023.
Development of a practical conversion factor for evaluating radioactivity in mixed metal and plastic clearance objects.
Appl Radiat Isot
January 2025
Tokyo City University, 1-28-1, Tamazutsumi, Setagaya-ku, Tokyo, 158-8557, Japan.
In clearance measurements involving a single material type, a conversion factor was applied to convert measurement results to activity based on an assumed uniform density. However, this factor has been found to underestimate activity in material mixtures. In this study, we proposed a method to identify the location with the lowest detection sensitivity (minimum location) in a mixture and evaluated its applicability to the conversion factor.
View Article and Find Full Text PDFHydropower Station diversion tunnel layered excavation deformation mechanism under high crustal stress.
Sci Rep
January 2025
Power China Guiyang Engineering Corporation Limited, Guiyang, China, 550081, Guizhou.
Aiming at the crucial engineering challenge of the ambiguous excavation deformation mechanism of hard and brittle surrounding rock under high geos-tress conditions, with the right bank diversion tunnel at the dam site of the hydropower station as the research object, the deformation and failure characteristics of the surrounding rock and their formation mechanisms during the layered excavation of the diversion tunnel were investigated. The research findings show: (1) The main factors influencing the deformation of the diversion tunnel's surrounding rock are the high ground stress environment, the degree of fracture development in the rock mass, and the effectiveness of the support system. (2) Following the excavation of the first layer, extensive shallow damage predominates, with damaged blocks primarily exhibiting sheet-like and plate-like forms.
View Article and Find Full Text PDFContextual cues can be used to predict the likelihood of and reduce interference from salient distractors.
Atten Percept Psychophys
January 2025
Department of Psychology, The Ohio State University, 1835 Neil Ave, Columbus, OH, 43210, USA.
Our attention can sometimes be disrupted by salient but irrelevant objects in the environment. This distractor interference can be reduced when distractors appear frequently, allowing us to anticipate their presence. However, it remains unknown whether distractor frequency can be learned implicitly across distinct contexts.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!