A Role of GABA Analogues in the Treatment of Neurological Diseases

Gajcy, Kamila; Lochyński, Stanisław; Librowski, Tadeusz

doi:10.2174/092986710791698549

Cited by 101 publications

(75 citation statements)

References 69 publications

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“…Mounting evidence implicates the GABAergic system, and specifically the tonic form of inhibition, as a potential therapeutic target for developing novel treatments for other brain disorders such as epilepsy, premenstrual dysphoric disorder and stroke [22,29,30,31]. In relation to FXS, it has been reported that GABA exposure during development can rescue the biochemical, morphological, and behavioral phenotypes of the Drosophila model of FXS [20], and taurine, a GABA A receptor agonist, improves cognitive functions in a mouse model of FXS [21].…”

Section: Discussionmentioning

confidence: 99%

The GABA<sub>A</sub> Receptor Agonist THIP Ameliorates Specific Behavioral Deficits in the Mouse Model of Fragile X Syndrome

2011

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Hyperactivity, hypersensitivity to auditory stimuli, and exaggerated fear are common behavioral abnormalities observed in individuals with fragile X syndrome (FXS), a neurodevelopmental disorder that is the most common genetic cause of autism. Evidence from studies of the Fmr1 knockout (KO) mouse model of FXS supports the notion that impaired GABAergic transmission in different brain regions such as the amygdala, striatum or cerebral cortex is central to FXS behavioral abnormalities. This suggests that the GABAergic system might be an intriguing target to ameliorate some of the phenotypes in FXS. Our recent work revealed that THIP (gaboxadol), a GABA_A receptor agonist, can restore principal neuron excitability deficits in the Fmr1 KO amygdala, suggesting that THIP may also restore some of the key behavioral abnormalities in Fmr1 KO mice. Here, we reveal that THIP significantly attenuated hyperactivity in Fmr1 KO mice, and reduced prepulse inhibition in a volume-dependent manner. In contrast, THIP did not reverse the deficits in cued fear or startle response. Thus, this study shows that enhancing GABAergic transmission can correct specific behavioral phenotypes of the Fmr1 KO mouse further supporting that targeting the GABAergic system, and specifically tonic inhibition, might be important for correcting or ameliorating some key behaviors in FXS.

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Section: Discussionmentioning

confidence: 99%

The GABA<sub>A</sub> Receptor Agonist THIP Ameliorates Specific Behavioral Deficits in the Mouse Model of Fragile X Syndrome

2011

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“…On the other hand, GABA has been shown as an antioxidant, blood sugar reducing and vasorelaxant agent (20,24,36-38). The renal tissues are documented to be involved in GABA synthesis and the kidneys are known to possess various subtypes of GABA receptors (39,40). It seems that GABA could be involved in regulating renal function.…”

Section: Discussionmentioning

confidence: 99%

Renoprotective effects of GABA on ischemia/reperfusion- induced renal injury in hyperglycemic male and female rats

Soltani¹,

Tighsaz²,

Nematbakhsh³

2017

hmj

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“…Normal brain function requires a balance between excitatory and inhibitory inputs that converge onto neurons in the central nervous system, with imbalance producing major neurological disorders (e.g., Gajcy et al, 2010; Naylor, 2010). Unilateral vestibular deafferentation destroys the balance in vestibular nuclei neurons by removing a major excitatory input.…”

Section: Spontaneous Synaptic Activity After Unilateral Peripheral Vementioning

confidence: 99%

Basic Concepts in Understanding Recovery of Function in Vestibular Reflex Networks during Vestibular Compensation

Peusner¹,

Shao²,

Reddaway³

et al. 2012

Front. Neur.

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Unilateral peripheral vestibular lesions produce a syndrome of oculomotor and postural deficits with the symptoms at rest, the static symptoms, partially or completely normalizing shortly after the lesion due to a process known as vestibular compensation. The symptoms are thought to result from changes in the activity of vestibular sensorimotor reflexes. Since the vestibular nuclei must be intact for recovery to occur, many investigations have focused on studying these neurons after lesions. At present, the neuronal plasticity underlying early recovery from the static symptoms is not fully understood. Here we propose that knowledge of the reflex identity and input–output connections of the recorded neurons is essential to link the responses to animal behavior. We further propose that the cellular mechanisms underlying vestibular compensation can be sorted out by characterizing the synaptic responses and time course for change in morphologically defined subsets of vestibular reflex projection neurons. Accordingly, this review focuses on the perspective gained by performing electrophysiological and immunolabeling studies on a specific subset of morphologically defined, glutamatergic vestibular reflex projection neurons, the principal cells of the chick tangential nucleus. Reference is made to pertinent findings from other studies on vestibular nuclei neurons, but no comprehensive review of the literature is intended since broad reviews already exist. From recording excitatory and inhibitory spontaneous synaptic activity in principal cells, we find that the rebalancing of excitatory synaptic drive bilaterally is essential for vestibular compensation to proceed. This work is important for it defines for the first time the excitatory and inhibitory nature of the changing synaptic inputs and the time course for changes in a morphologically defined subset of vestibular reflex projection neurons during early stages of vestibular compensation.

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A Role of GABA Analogues in the Treatment of Neurological Diseases

Cited by 101 publications

References 69 publications

The GABA<sub>A</sub> Receptor Agonist THIP Ameliorates Specific Behavioral Deficits in the Mouse Model of Fragile X Syndrome

The GABA<sub>A</sub> Receptor Agonist THIP Ameliorates Specific Behavioral Deficits in the Mouse Model of Fragile X Syndrome

Renoprotective effects of GABA on ischemia/reperfusion- induced renal injury in hyperglycemic male and female rats

Basic Concepts in Understanding Recovery of Function in Vestibular Reflex Networks during Vestibular Compensation

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