Altered GABAergic Signaling in Brain Disease at Various Stages of Life

Kim, Yoo Sung; Yoon, Bo Eun

doi:10.5607/en.2017.26.3.122

Cited by 54 publications

(44 citation statements)

References 82 publications

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“…The diversity in GABAergic signaling is due to several peri‐, pre‐, and postsynaptic factors (Figure B) that are the target of many drugs that are currently in wide clinical use . It is also well documented that an alteration in any aspect of this system is linked to several neurological and neurodevelopmental disorders . GABA A Rs are the main inhibitory receptors in the brain, and their heteromeric structure contributes in several ways to the physiological properties of brain GABAergic neurotransmission.…”

Section: Gabaergic Neurotransmissionmentioning

confidence: 99%

“…31,32 It is also well documented that an alteration in any aspect of this system is linked to several neurological and neurodevelopmental disorders. [33][34][35][36][37][38][39][40] GABA A Rs are the main inhibitory receptors in the brain, and their heteromeric structure contributes in several ways to the physiological properties of brain GABAergic neurotransmission. GABA also acts on GABA B Rs which have different molecular and functional properties to those of GABA A Rs (eg, see 41 ).…”

Section: G Abaer Gic Neurotr Ans Miss Ionmentioning

confidence: 99%

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Alteration of GABAergic neurotransmission in Huntington's disease

Garret

Chazalon

et al. 2018

CNS Neurosci Ther

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Hereditary Huntington's disease (HD) is characterized by cell dysfunction and death in the brain, leading to progressive cognitive, psychiatric, and motor impairments. Despite molecular and cellular descriptions of the effects of the HD mutation, no effective pharmacological treatment is yet available. In addition to well-established alterations of glutamatergic and dopaminergic neurotransmitter systems, it is becoming clear that the GABAergic systems are also impaired in HD. GABA is the major inhibitory neurotransmitter in the brain, and GABAergic neurotransmission has been postulated to be modified in many neurological and psychiatric diseases. In addition, GABAergic neurotransmission is the target of many drugs that are in wide clinical use. Here, we summarize data demonstrating the occurrence of alterations of GABAergic markers in the brain of HD carriers as well as in rodent models of the disease. In particular, we pinpoint HD-related changes in the expression of GABA receptors (GABA Rs). On the basis that a novel GABA pharmacology of GABA Rs established with more selective drugs is emerging, we argue that clinical treatments acting specifically on GABAergic neurotransmission may be an appropriate strategy for improving symptoms linked to the HD mutation.

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Section: Gabaergic Neurotransmissionmentioning

confidence: 99%

Section: G Abaer Gic Neurotr Ans Miss Ionmentioning

confidence: 99%

Alteration of GABAergic neurotransmission in Huntington's disease

Garret

Chazalon

et al. 2018

CNS Neurosci Ther

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“…Therefore, the research model for AD with an APP Swedish mutation is now widely used [50][51][52][53], and the H4SW cell line is called the AD in vitro model [20]. Moreover, Aβ accumulated in the brain of AD patients activates glia cells, which are known to eliminate Aβ and have neuroprotective effects [54][55][56][57]. MSCs do not remove Aβ itself when exposed to AD but secrete proteins that can stimulate neurons or glial cells through paracrine action [58].…”

Section: Discussionmentioning

confidence: 99%

Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects

Park

Kim²,

Kwon³

et al. 2020

Preprint

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BackgroundMesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of Alzheimer’s disease (AD). Previous studies suggested that the co-culture of human MSCs with AD in an in vitro model reduced the expression of amyloid-beta 42 (Aβ42) in the medium as well as the overexpression of amyloid-beta (Aβ )-degrading enzymes such as neprilysin (NEP).MethodsIn this study, we focused on the role of primed MSCs (human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) exposed to an AD cell line via a co-culture system) in reducing the levels of Aβ and inhibiting cell death. ResultsWe demonstrated that mouse groups treated with naïve MSCs and primed MSCs showed significant reductions in cell death, ubiquitin conjugate levels, and Aβ levels, but the effects were greater in primed MSCs. Also, mRNA sequencing data analysis indicated that high levels of TGF-β induced primed-MSCs. Furthermore, treatment with TGF-β reduced Aβ expression in an AD transgenic mouse model. ConclusionAD environmental preconditioning is a promising strategy to reduce cell death and ubiquitin conjugate levels and maintain the stemness of MSCs. Further, these data suggest that human WJ-MSCs exposed to an AD environment may represent a promising and novel therapy for AD.

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“…However, there are some key points germane to the discussion below. First, the cycle is highly dependent on energy supplied by glucose oxidation and optimal mitochondrial function [200]. Second, KBs are the preferred oxidative substrate for "powering" the glutamate-glutamine cycle in the environment of cerebral glucose hypometabolism seen in neurodegenerative and neuroprogressive disorders [201].…”

Section: Effect Of Nutritional Ketosis On the Astrocyte Glutamate-glumentioning

confidence: 99%

Nutritional ketosis as an intervention to relieve astrogliosis: Possible therapeutic applications in the treatment of neurodegenerative and neuroprogressive disorders

et al. 2020

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Nutritional ketosis, induced via either the classical ketogenic diet or the use of emulsified medium-chain triglycerides, is an established treatment for pharmaceutical resistant epilepsy in children and more recently in adults. In addition, the use of oral ketogenic compounds, fractionated coconut oil, very low carbohydrate intake, or ketone monoester supplementation has been reported to be potentially helpful in mild cognitive impairment, Parkinson’s disease, schizophrenia, bipolar disorder, and autistic spectrum disorder. In these and other neurodegenerative and neuroprogressive disorders, there are detrimental effects of oxidative stress, mitochondrial dysfunction, and neuroinflammation on neuronal function. However, they also adversely impact on neurone–glia interactions, disrupting the role of microglia and astrocytes in central nervous system (CNS) homeostasis. Astrocytes are the main site of CNS fatty acid oxidation; the resulting ketone bodies constitute an important source of oxidative fuel for neurones in an environment of glucose restriction. Importantly, the lactate shuttle between astrocytes and neurones is dependent on glycogenolysis and glycolysis, resulting from the fact that the astrocytic filopodia responsible for lactate release are too narrow to accommodate mitochondria. The entry into the CNS of ketone bodies and fatty acids, as a result of nutritional ketosis, has effects on the astrocytic glutamate–glutamine cycle, glutamate synthase activity, and on the function of vesicular glutamate transporters, EAAT, Na+, K+-ATPase, Kir4.1, aquaporin-4, Cx34 and KATP channels, as well as on astrogliosis. These mechanisms are detailed and it is suggested that they would tend to mitigate the changes seen in many neurodegenerative and neuroprogressive disorders. Hence, it is hypothesized that nutritional ketosis may have therapeutic applications in such disorders.

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Altered GABAergic Signaling in Brain Disease at Various Stages of Life

Cited by 54 publications

References 82 publications

Alteration of GABAergic neurotransmission in Huntington's disease

Alteration of GABAergic neurotransmission in Huntington's disease

Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects

Nutritional ketosis as an intervention to relieve astrogliosis: Possible therapeutic applications in the treatment of neurodegenerative and neuroprogressive disorders

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