Aging and GABA

Cuypers, Koen; Maes, Celine; Swinnen, Stephan P.

doi:10.18632/aging.101480

Cited by 20 publications

(13 citation statements)

References 7 publications

(9 reference statements)

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“…Although we have no satisfactory explanation for adult onset seizure, it is possible that malfunction of GABAergic neurons caused by the lack of PLCγ1 could not induce the critical defects in the developmental and early postnatal stages, but as Plcg1 F/F ; Dlx5/6-Cre mice get older, the damages given to GABAergic neurons would be accelerated and gradually accumulated in hippocampal circuit. When these accumulated damages reach a certain threshold, it might result in the attenuation of synaptic inhibition through reduced GABAergic tone in the hippocampus in middle age and more elderly brain 49 .…”

Section: Discussionmentioning

confidence: 99%

Deletion of PLCγ1 in GABAergic neurons increases seizure susceptibility in aged mice

Kim

Yang

Hwang

et al. 2019

Sci Rep

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Synaptic inhibition plays a fundamental role in the information processing of neural circuits. It sculpts excitatory signals and prevents hyperexcitability of neurons. Owing to these essential functions, dysregulated synaptic inhibition causes a plethora of neurological disorders, including epilepsy, autism, and schizophrenia. Among these disorders, epilepsy is associated with abnormal hyperexcitability of neurons caused by the deficits of GABAergic neuron or decreased GABAergic inhibition at synapses. Although many antiepileptic drugs are intended to improve GABA-mediated inhibition, the molecular mechanisms of synaptic inhibition regulated by GABAergic neurons are not fully understood. Increasing evidence indicates that phospholipase Cγ1 (PLCγ1) is involved in the generation of seizure, while the causal relationship between PLCγ1 and seizure has not been firmly established yet. Here, we show that genetic deletion of PLCγ1 in GABAergic neurons leads to handling-induced seizure in aged mice. In addition, aged Plcg1F/F; Dlx5/6-Cre mice exhibit other behavioral alterations, including hypoactivity, reduced anxiety, and fear memory deficit. Notably, inhibitory synaptic transmission as well as the number of inhibitory synapses are decreased in the subregions of hippocampus. These findings suggest that PLCγ1 may be a key determinant of maintaining both inhibitory synapses and synaptic transmission, potentially contributing to the regulation of E/I balance in the hippocampus.

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Section: Discussionmentioning

confidence: 99%

Deletion of PLCγ1 in GABAergic neurons increases seizure susceptibility in aged mice

Kim

Yang

Hwang

et al. 2019

Sci Rep

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“…The balance between inhibitory neuronal transmission via GABA and excitatory neuronal transmission via glutamate is essential for proper cell membrane stability and neurologic function. GABA is conjectured to have effects on motor performance and cognitive functioning because a decrease of GABA levels in elderly patients seems to be associated to the deterioration of these abilities [ 109 ]. It also plays a role as a source of energy, generating ATP in the tricarboxylic acid cycle in the mitochondria [ 110 ].…”

Section: Gamma-aminobutyric Acidmentioning

confidence: 99%

Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management

Gros¹,

Gros²,

Mesonero

et al. 2021

JCM

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Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder whose aetiology is still unknown. Most hypotheses point out the gut-brain axis as a key factor for IBS. The axis is composed of different anatomic and functional structures intercommunicated through neurotransmitters. However, the implications of key neurotransmitters such as norepinephrine, serotonin, glutamate, GABA or acetylcholine in IBS are poorly studied. The aim of this review is to evaluate the current evidence about neurotransmitter dysfunction in IBS and explore the potential therapeutic approaches. IBS patients with altered colorectal motility show augmented norepinephrine and acetylcholine levels in plasma and an increased sensitivity of central serotonin receptors. A decrease of colonic mucosal serotonin transporter and a downregulation of α2 adrenoceptors are also correlated with visceral hypersensitivity and an increase of 5-hydroxyindole acetic acid levels, enhanced expression of high affinity choline transporter and lower levels of GABA. Given these neurotransmitter dysfunctions, novel pharmacological approaches such as 5-HT3 receptor antagonists and 5-HT4 receptor agonists are being explored for IBS management, for their antiemetic and prokinetic effects. GABA-analogous medications are being considered to reduce visceral pain. Moreover, agonists and antagonists of muscarinic receptors are under clinical trials. Targeting neurotransmitter dysfunction could provide promising new approaches for IBS management.

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“…In contrast, much less attention has been devoted to the effect of short-term transient lesions induced by short-train rTMS. Pharmacological or magnetic resonance spectroscopy (MRS) imaging techniques are needed to examine the role of gamma-aminobutyric acid (GABA), a principal inhibitory neurotransmitter, for explaining the local, transient suppressing effect of short-train rTMS (Cuypers et al, 2018;Pauwels et al, 2018). Insight in these mechanisms will be crucial to further explore the involvement of DLPFC in bimanual coordination.…”

Section: Limitations and Future Directionsmentioning

confidence: 99%

Induced Suppression of the Left Dorsolateral Prefrontal Cortex Favorably Changes Interhemispheric Communication During Bimanual Coordination in Older Adults–A Neuronavigated rTMS Study

Verstraelen

Dun

Duque

et al. 2020

Front. Aging Neurosci.

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Recent transcranial magnetic stimulation (TMS) research indicated that the ability of the dorsolateral prefrontal cortex (DLPFC) to disinhibit the contralateral primary motor cortex (M1) during motor preparation is an important predictor for bimanual motor performance in both young and older healthy adults. However, this DLPFC-M1 disinhibition is reduced in older adults. Here, we transiently suppressed left DLPFC using repetitive TMS (rTMS) during a cyclical bimanual task and investigated the effect of left DLPFC suppression:(1) on the projection from left DLPFC to the contralateral M1; and (2) on motor performance in 21 young (mean age ± SD = 21.57 ± 1.83) and 20 older (mean age ± SD = 69.05 ± 4.48) healthy adults. As predicted, without rTMS, older adults showed compromised DLPFC-M1 disinhibition as compared to younger adults and less preparatory DLPFC-M1 disinhibition was related to less accurate performance, irrespective of age. Notably, rTMS-induced DLPFC suppression restored DLPFC-M1 disinhibition in older adults and improved performance accuracy right after the local suppression in both age groups. However, the rTMS-induced gain in disinhibition was not correlated with the gain in performance. In sum, this novel rTMS approach advanced our mechanistic understanding of how left DLPFC regulates right M1 and allowed us to establish the causal role of left DLPFC in bimanual coordination.

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Aging and GABA

Cited by 20 publications

References 7 publications

Deletion of PLCγ1 in GABAergic neurons increases seizure susceptibility in aged mice

Deletion of PLCγ1 in GABAergic neurons increases seizure susceptibility in aged mice

Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management

Induced Suppression of the Left Dorsolateral Prefrontal Cortex Favorably Changes Interhemispheric Communication During Bimanual Coordination in Older Adults–A Neuronavigated rTMS Study

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