High Dose Gamma Radiation Selectively Reduces GABAA-slow Inhibition

Dagne, Beza A; Sunay, Melis K; Cayla, Noëlie S; Ouyang, Yi‐Bing; Knox, Susan J.; Giffard, Rona G.; Adler, John R.; MacIver, M Bruce

doi:10.7759/cureus.1076

Cited by 5 publications

(3 citation statements)

References 32 publications

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“…NPY is a neuropeptide neurotransmitter in both the brain and the autonomic nervous system which has roles in stress, food intake, obesity, and seizures [ 22 ]. The decrease of NPY-positive neurons in this study agrees with results of the electrophysiology study we published which used the same radiation protocol in the same age and strain of rat [ 23 ].…”

Section: Discussionsupporting

confidence: 89%

Alteration of Interneuron Immunoreactivity and Autophagic Activity in Rat Hippocampus after Single High-Dose Whole-Brain Irradiation

Ouyang

Ning

Adler

et al. 2017

Cureus

Self Cite

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The effects of high dose gamma radiation on brain tissue are poorly understood, with both limited and major changes reported. The present study compared the effects of gamma irradiation on the expression of interneuron markers within the hippocampal cornu ammonis 1 (CA1) region with expression in control matched rats. This area was chosen for study because of its well-characterized circuitry. Male Sprague-Dawley rats were exposed to 60 Gy of whole brain gamma radiation and after 24 or 48 hours, the brains were removed, fixed and sectioned to quantitate expression of parvalbumin (PV), calbindin-D28K (CB), reelin, neuropeptide-Y (NPY), and somatostatin. All of these markers increased in expression over the first 48 hours, except NPY, which decreased. This provides novel information on changes in gene expression in the hippocampal interneurons following radiation. Staining for Beclin 1, a marker of autophagy, increased most strongly in the subgranular zone (SGZ) of the dentate gyrus (DG). Overall, the results are consistent with the hypothesis that increased intracellular calcium follows irradiation, leading to an increased expression of calcium binding proteins. Increased autophagy occurs in the neurogenic zone of the dentate hilus, consistent with reduced effective neurogenesis after irradiation.

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Section: Discussionsupporting

confidence: 89%

Alteration of Interneuron Immunoreactivity and Autophagic Activity in Rat Hippocampus after Single High-Dose Whole-Brain Irradiation

Ouyang

Ning

Adler

et al. 2017

Cureus

Self Cite

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“…In Vitro Brain Slice Electrophysiology: Extracellular Recordings. Hippocampal brain slices were prepared from male Sprague-Dawley rats (Charles River Laboratories, Wilmington, MA) as described elsewhere (34). Briefly, rats were deeply anesthetized with isoflurane before decapitation.…”

Section: Lorr Ed50 43 Mg/kg Lorr Ed50 43 Mg/kg Lorr Ed50 43 Mg/kgmentioning

confidence: 99%

A newly developed anesthetic based on a unique chemical core

Cayla

Dagne

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Intravenous anesthetic agents are associated with cardiovascular instability and poorly tolerated in patients with cardiovascular disease, trauma, or acute systemic illness. We hypothesized that a new class of intravenous (IV) anesthetic molecules that is highly selective for the slow type of γ-aminobutyric acid type A receptor (GABAAR) could have potent anesthetic efficacy with limited cardiovascular effects. Through in silico screening using our GABAAR model, we identified a class of lead compounds that are N-arylpyrrole derivatives. Electrophysiological analyses using both an in vitro expression system and intact rodent hippocampal brain slice recordings demonstrate a GABAAR-mediated mechanism. In vivo experiments also demonstrate overt anesthetic activity in both tadpoles and rats with a potency slightly greater than that of propofol. Unlike the clinically approved GABAergic anesthetic etomidate, the chemical structure of our N-arylpyrrole derivative is devoid of the chemical moieties producing adrenal suppression. Our class of compounds also shows minimal to no suppression of blood pressure, in marked contrast to the hemodynamic effects of propofol. These compounds are derived from chemical structures not previously associated with anesthesia and demonstrate that selective targeting of GABAAR-slow subtypes may eliminate the hemodynamic side effects associated with conventional IV anesthetics.

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“…27 Some studies have reported that ionizing irradiation affects GABAergic neurotransmission, including PV neurons. 28,29 Recently, it was demonstrated that PV immunopositive interneurons in the hippocampus were the key components of intrinsic hippocampal y-oscillators. 30 These interneurons were vulnerable to oxidative stress including radiation exposure.…”

Section: Irradiation Induces the Impairment Of Neurogenesis And The Cmentioning

confidence: 99%

The Neuroprotective Effect of Amitriptyline on Radiation-Induced Impairment of Hippocampal Neurogenesis

et al. 2019

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The radioprotective effect of amitriptyline, an inhibitor of acid sphingomyelinase (ASMase), on radiation-induced impairment of hippocampal neurogenesis, loss of interneuron, and animal weight changes was investigated in BALB/c mice by immunostaining of biomarkers for cell division (Ki67), immature neurons (doublecortin or DCX), and interneurons (parvalbumin or PV) in the dentate gyrus (DG) of hippocampus. The results indicated that preirradiation (with 10 mg/kg, 2 times per day, for 7 consecutive days) or postirradiation (with 10 mg/kg, 2 times per day, for 14 consecutive days) treatment (pretreatment or posttreatment) with intraperitoneal injection of amitriptyline prevented the loss of newly generated neurons, proliferating cells, and interneurons in the subgranular zone of the DG. At the molecular level, pretreatment or posttreatment inhibited the expression of sphingomyelin phosphodiesterase 1 ( SMPD1) gene which codes for ASMase. The pretreatment for 7 days also prevented radiation-induced weight loss from 2 to 3 weeks, but not within 1 week after irradiation. On the other hand, the posttreatment with amitriptyline for 14 days could improve animal weight gain from 4 to 6 weeks after irradiation. The present study suggests that amitriptyline may be a promising candidate radio-neuroprotective drug to improve radiation-induced impairment of hippocampal neurogenesis and relevant neurological and neuropsychological disorders.

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High Dose Gamma Radiation Selectively Reduces GABAA-slow Inhibition

Cited by 5 publications

References 32 publications

Alteration of Interneuron Immunoreactivity and Autophagic Activity in Rat Hippocampus after Single High-Dose Whole-Brain Irradiation

Alteration of Interneuron Immunoreactivity and Autophagic Activity in Rat Hippocampus after Single High-Dose Whole-Brain Irradiation

A newly developed anesthetic based on a unique chemical core

The Neuroprotective Effect of Amitriptyline on Radiation-Induced Impairment of Hippocampal Neurogenesis

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