Adult neurogenesis is the multistage process of generating neurons from adult neural stem cells. Accumulating evidence indicates that GABAergic depolarization is an important regulator of this process. Here, we examined GABAergic signaling to newly generated granule cells (GCs) of the adult mouse dentate gyrus. We show that the first synaptic currents in newborn GCs are generated by activation of GABA(A) receptors by GABA with a spatiotemporal profile suggestive of transmitter spillover. However, the GABAergic response is not attributable to spillover from surrounding perisomatic synapses. Rather, our results suggest that slow synaptic responses in newborn GCs are generated by dedicated inputs that produce a relatively low concentration of GABA at postsynaptic receptors, similar to slow IPSCs in mature GCs. This form of synaptic signaling drives robust phasic depolarization of newborn GCs when the interneuron network is synchronously active, revealing a potential mechanism that translates hippocampal activity into regulation of adult neurogenesis via synaptic release of GABA.
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http://dx.doi.org/10.1523/JNEUROSCI.2727-09.2009 | DOI Listing |
PNAS Nexus
January 2025
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA.
Bronchopulmonary dysplasia, the most prevalent chronic lung disease of prematurity, is often treated with glucocorticoids (GCs) such as dexamethasone (DEX), but their use is encumbered with several adverse somatic, metabolic, and neurologic effects. We previously reported that systemic delivery of the GC prodrug ciclesonide (CIC) in neonatal rats activated glucocorticoid receptor (GR) transcriptional responses in lung but did not trigger multiple adverse effects caused by DEX. To determine whether limited systemic metabolism of CIC was solely responsible for its enhanced safety profile, we treated neonatal rats with its active metabolite desisobutyryl-ciclesonide (Des-CIC).
View Article and Find Full Text PDFGenet Med Open
August 2024
Department of Pediatrics, Harvard Medical School, Boston, MA.
Purpose: There is growing international interest in using genomic sequencing to screen newborns and children for treatable genomic conditions. Although recent research has demonstrated increasing support for using genomic sequencing to screen newborns and children for treatable genomic conditions among various stakeholders, little is known about the perspectives of genetic counselors (GCs) in the United States, who are frequently engaged in the disclosure of positive newborn screening results and coordination of follow-up testing and management.
Methods: This study utilized a cross-sectional 3-section survey to explore GCs' perspectives on the benefits, limitations, and ethical and practical considerations of genomic sequencing in newborns as an adjunct screen to standard newborn screening (NBS).
Ecotoxicol Environ Saf
December 2024
Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S10 2SF, UK. Electronic address:
The ovarian reserve consists of a limited supply of primordial follicles (PFs), each containing an oocyte surrounded by a layer of granulosa cells (GCs). PFs are relatively quiescent and must remain viable for a long period, thereby making them susceptible to environmental and lifestyle influences. Given the widespread prevalence of e-cigarette use, this study aimed to investigate the effects of nicotine and its metabolite cotinine in a mouse model and to elucidate the mechanisms by which nicotine influences the ovarian reserve.
View Article and Find Full Text PDFJ Genet Couns
October 2024
Division of Medical Genetics, Department of Pediatrics, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
As awareness of the value of genetic counseling services increases, there has been greater recognition of the need to diversify service delivery into different languages. Studies within genetic counseling and related fields have identified complications that can arise from language nonconcordance between provider and patient. A strategy to mitigate language barriers is prioritizing the development of a multilingual workforce of genetic counselors (GCs) who can communicate with patients in their preferred language.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2024
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
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