Heterogeneous subpopulations of GABAAR-responding neurons coexist in physiological and pathological mature neuronal networks at increasing scales of complexity DOI Open Access
Ilaria Colombi, Mansi Rastogi,

Martina Parrini

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 26, 2023

ABSTRACT GABA is the main inhibitory neurotransmitter in adults. Depolarizing/excitatory responses have been well characterized at level of neuronal-population average during typical neurodevelopment and partially pathology. However, no investigation has specifically assessed whether a mosaicism cells with either depolarizing/excitatory or hyperpolarizing/inhibitory GABAergic exists adult animals health/disease. Here, we showed that such present both WT Down syndrome (DS) mice, as increasing scales neuronal-network complexity (cultures, brain- slices, behaving mice). Nevertheless, mice presented lower percentage depolarizing than DS mice. Restoring hyperpolarizing GABA-responding neurons to levels rescued anxiety behaviour We also found heterogeneous mature control trisomic human iPSC-derived neurons. Thus, population physiological/pathological conditions mouse neurons, possibly contributing disease-associated behaviours.

Language: Английский

A paradoxical switch: the implications of excitatory GABAergic signaling in neurological disorders DOI Creative Commons

Colin J. McArdle,

Alana A. Arnone, Chelcie F. Heaney

et al.

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 10, 2024

Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in central nervous system. In mature brain, GABAergic signaling critical maintaining neuronal homeostasis and vital human behaviors such as cognition, emotion, motivation. While classically known to inhibit function under physiological conditions, previous research indicates a paradoxical switch from excitatory that implicated several neurological disorders. Various mechanisms have been proposed contribute chloride ion dyshomeostasis, alterations receptor expression, modifications synaptic plasticity. Of note, hypothesized underlying are highlighted number of neurodevelopmental, substance use, stress, neurodegenerative Herein, we present an updated review discussing presence various disorders, their potential contributions towards disease pathology.

Language: Английский

Citations

10
Aperiodic and Hurst EEG exponents across early human brain development: A systematic review DOI Creative Commons
Ryan A. Stanyard, Dan Mason, Claire L. Ellis

et al.

Developmental Cognitive Neuroscience, Journal Year: 2024, Volume and Issue: 68, P. 101402 - 101402

Published: June 7, 2024

In electroencephalographic (EEG) data, power-frequency slope exponents (1/f_β) can provide non-invasive markers of in vivo neural activity excitation-inhibition (E:I) balance. E:I balance may be altered neurodevelopmental conditions; hence, understanding how 1/f β evolves across infancy/childhood has implications for developing early assessments/interventions. This systematic review (PROSPERO-ID: CRD42023363294) explored the maturation (0-26 yrs) resting-state EEG measures (aperiodic [AE], power law [PLE] and Hurst [HE] exponents), including studies containing ≥1 ≥10 typically participants. Five databases (including Embase Scopus) were searched during March 2023. Forty-two identified (Nparticipants=3478). Risk bias was assessed using Quality Assessment with Diverse Studies tool. Narrative synthesis HE data suggests non-stationary occurs throughout development. Age-related trends complex, rapid decreases AEs infancy heterogenous changes thereafter. Regionally, AE maxima shifted developmentally, potentially reflecting spatial maturing brain connectivity. work highlights importance further characterising development to better understand shapes cognitive

Language: Английский

Citations

7
Torasemide Improves the Propionic Acid-Induced Autism in Rats: A Histopathological and Imaging Study DOI
Murat Doğan, Yakup Albayrak, Oytun Erbaş

et al.

ALPHA PSYCHIATRY, Journal Year: 2023, Volume and Issue: 24(1), P. 22 - 31

Published: Jan. 10, 2023

Autism spectrum disorder is a neurodevelopmental disease in which impaired social behaviors, sociality, and restricted repetitive behaviors are seen. Bumetanide loop diuretic that inhibits Na+-K+-2Cl- cotransporter 1 it currently used clinical phase studies patients with autism disorder. In present research, purposed to demonstrate the beneficial effects of torasemide another inhibitor on an experimental model induced propionic acid by providing imaging brain tissue investigations. Male Wistar rats were study (n = 30). Propionic 250 mg/kg/day was administrated intraperitoneally induce for 5 days. Three groups created as follows: group 1, normal control 10); 2, saline given 3, + tora-semide-administrated 10). Torasemide scored higher behavioral tests compared group. The levels malondialdehyde, tumor necrosis factor-alpha, interleukin-2, interleukin-17, Nuclear Factor kappa B (NF-κB), Glial fibrillary acidic protein (GFAP) remarkably histopathology assessments, had neuronal count Cornu Ammonis 2 hippocampus, Purkinje cells cerebellum. GFAP immunostaining index (Cornu 1) cerebellum lower Magnetic resonance spectroscopy revealed mean lactate value Our results showed might enhance gamma-aminobutyric activity. can be considered promising treatment longer half-life less side after further studies.

Language: Английский

Citations

15
GABAergic system and chloride cotransporters as potential therapeutic targets to mitigate cell death in ischemia DOI
Amary Nascimento,

Danniel Pereira‐Figueiredo,

Vladimir Pedro Peralva Borges-Martins

et al.

Journal of Neuroscience Research, Journal Year: 2024, Volume and Issue: 102(5)

Published: May 1, 2024

Gamma aminobutyric acid (GABA) is a critical inhibitory neurotransmitter in the central nervous system that plays vital role modulating neuronal excitability. Dysregulation of GABAergic signaling, particularly involving cotransporters NKCC1 and KCC2, has been implicated various pathologies, including epilepsy, schizophrenia, autism spectrum disorder, Down syndrome, ischemia. facilitates chloride influx, whereas KCC2 mediates efflux via potassium gradient. Altered expression function these have associated with excitotoxicity, inflammation, cellular death ischemic events characterized by reduced cerebral blood flow, leading to compromised tissue metabolism subsequent cell death. inhibition emerged as potential therapeutic approach attenuate intracellular accumulation mitigate damage during events. Similarly, targeting which regulates efflux, holds promise for improving outcomes reducing under conditions. This review emphasizes roles GABA, NKCC1, pathologies their targets. Inhibiting or activity represents promising strategy damage, preventing neurological following Furthermore, exploring interactions between natural compounds NKCC1/KCC2 provides additional avenues interventions injury.

Language: Английский

Citations

6
The NKCC1 inhibitor bumetanide restores cortical feedforward inhibition and lessens sensory hypersensitivity in early postnatal fragile X mice. DOI
Nazim Kourdougli,

Toshihiro Nomura,

M. Wu

et al.

Biological Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Language: Английский

Citations

6
The Newborn's Reaction to Light as the Determinant of the Brain's Activation at Human Birth DOI Creative Commons
Daniela Polese, Maria Letizia Riccio,

Marcella Fagioli

et al.

Frontiers in Integrative Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: Sept. 2, 2022

Developmental neuroscience research has not yet fully unveiled the dynamics involved in human birth. The trigger of first breath, often assumed to be marker life, been characterized nor process entailing brain modification and activation at birth clarified yet. To date, few researchers only have investigated impact extrauterine environment, with its strong stimuli, on This 'hypothesis theory' article assumes role a specific stimulus activating central nervous system (CNS) must features though, such as novelty, efficacy, ubiquity, immediacy. We propose light robust candidate for CNS via retina. Available data fetal neonatal neurodevelopment, particular reference retinal light-responsive pathways, will examined together GABA functional switch, subplate disappearance, which, an experimental level, differentiate from brain. In this study, we assume how very rapid photoreceptors initiates sudden shift prenatal pattern functions setup. Our assumption implies presence photoreceptor capable capturing transducing light/photon stimulus, transforming it into effective signal new Opsin photoreception or, more specifically, melanopsin-dependent photoreception, which is provided by intrinsically photosensitive ganglion cells (ipRGCs), considered valid candidate. Although what herein cannot verified humans based knowledge available so far, proposing important novel function can broad range diversified different domains, neurophysiology neurology psychiatry.

Language: Английский

Citations

17
Heterogeneous subpopulations of GABAAR-responding neurons coexist across neuronal network scales and developmental stages in health and disease DOI Creative Commons
Ilaria Colombi, Mohit Rastogi,

Martina Parrini

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(4), P. 109438 - 109438

Published: March 8, 2024

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in adults. Depolarizing GABA responses have been well characterized at neuronal-population

Language: Английский

Citations

3
Iconography of abnormal non-neuronal cells in pediatric focal cortical dysplasia type IIb and tuberous sclerosis complex DOI Creative Commons

Joyce Zhang,

Deneen Argueta,

Xiaoping Tong

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 18

Published: Jan. 6, 2025

Once believed to be the culprits of epileptogenic activity, functional properties balloon/giant cells (BC/GC), commonly found in some malformations cortical development including focal dysplasia type IIb (FCDIIb) and tuberous sclerosis complex (TSC), are beginning unraveled. These abnormal emerge during early brain as a result hyperactive mTOR pathway may express both neuronal glial markers. A paradigm shift occurred when our group demonstrated that BC/GC pediatric cases FCDIIb TSC unable generate action potentials lack synaptic inputs. Hence, their role epileptogenesis remained obscure. In this review, we provide detailed characterization non-neuronal BC/GC, intermediate cells, dysmorphic/reactive astrocytes cases, with special emphasis on electrophysiological morphological assessments. Regardless pathology, appear more glial-like, while others neuronal-like. Their morphology also differs terms somatic size, shape, dendritic elaboration. common feature these types is inability potentials. Thus, despite distinct etiologies, they share feature. We hypothesize that, although exact remains mysterious, it can suggested displaying glial-like function similar way do, i.e., buffer K+ ions neurotransmitters, those properties, represent metabolic burden due high energy demands but receive or transmit electric signals. addition, heterogeneity new classification scheme based morphological, electrophysiological, gene/protein expression seems warranted.

Language: Английский

Citations

0
Neurodevelopment at 10 months and 2–3 years old after early and prolonged anaesthesia in infancy: General Anaesthesia & Brain Activity study (GABA) secondary analysis DOI
Laura Cornelissen, Siobhan Coffman,

Isabelle Kim

et al.

BJA Open, Journal Year: 2025, Volume and Issue: 14, P. 100383 - 100383

Published: March 10, 2025

Language: Английский

Citations

0
Modulation of GABAergic System in a Chicken Retinal Ischemic Model: The Role of Chloride Cotransporters DOI Creative Commons
Amary Nascimento,

V. S. Miya‐Coreixas,

Daniel Souza Monteiro de Araújo

et al.

Journal of Neuroscience Research, Journal Year: 2025, Volume and Issue: 103(5)

Published: May 1, 2025

ABSTRACT Retinal ischemia is a significant pathological condition that contributes to visual impairment and neuronal cell death in various retinopathies. Evidence suggests GABA release during ischemic events may exhibit neuroprotective properties, but conflicting findings highlight potential shift its effects due altered chloride ion homeostasis. This study aimed investigate the role of GABAergic system retinal ischemia, focusing on temporal dynamics impact damage. We hypothesized ischemia‐induced changes transport equilibrium contribute damage, which can be mitigated by modulating activity. Using an ex vivo chick retina model subjected oxygen glucose deprivation (OGD), different times, we assessed morphological changes, death, levels, transporter activity, levels cotransporters NKCC1 KCC2. Pharmacological interventions, including picrotoxin bumetanide, were used evaluate effects. Our results revealed OGD‐induced retina. reduced GAT‐1‐dependent manner, while bumetanide demonstrated mitigating swelling system. Notably, OGD increased content, not KCC2 indicating disruption These suggest alterations activity Targeting these pathways with pharmacological agents, such as offer therapeutic strategies for injury. Further research recommended explore clinical applicability

Language: Английский

Citations

0