Post-Traumatic Stress Disorder Chronification via Monoaminooxidase and Cortisol Metabolism

Tseĭlikman, Vadim; Dremencov, Eliyahu; Maslennikova, Ekaterina; Ishmatova, Alla; Манухина, Е. Б.; Downey, H. Fred; Klebanov, Igor R.; Tseilikman, Olga; Komelkova, Maria; Lapshin, Maxim; Vasilyeva, M. V.; Bornstein, Stefan R.; Perry, Seth W.; Wong, Ma Li; Licinio, Júlio; Yehuda, Rachel; Ullmann, Enrico

doi:10.1055/a-0975-9268

Cited by 13 publications

(15 citation statements)

References 26 publications

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“…Stress induced by traumatic events and resultant PTSD are recognized as a risk factor for Alzheimer's disease [68,69]. The PTSD-induced NE accumulation results from suppressed activity and expression of monoaminoxidase A (MAO-A), a key mediator of biogenic amine metabolism [70]. Our finding of increased NE and reduced MAO-A activity in the cortex of rats with experimental PTSD are consistent with these data.…”

Section: Discussionsupporting

confidence: 87%

Intermittent Hypoxic Conditioning Alleviates Post-Traumatic Stress Disorder-Induced Damage and Dysfunction of Rat Visceral Organs and Brain

Манухина

Tseĭlikman

Karpenko

et al. 2020

IJMS

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Posttraumatic stress disorder (PTSD) causes mental and somatic diseases. Intermittent hypoxic conditioning (IHC) has cardio-, vaso-, and neuroprotective effects and alleviates experimental PTSD. IHC’s ability to alleviate harmful PTSD effects on rat heart, liver, and brain was examined. PTSD was induced by 10-day exposure to cat urine scent (PTSD rats). Some rats were then adapted to 14-day IHC (PTSD+IHC rats), while PTSD and untreated control rats were cage rested. PTSD rats had a higher anxiety index (AI, X-maze test), than control or PTSD+IHC rats. This higher AI was associated with reduced glycogen content and histological signs of metabolic and hypoxic damage and of impaired contractility. The livers of PTSD rats had reduced glycogen content. Liver and blood alanine and aspartate aminotransferase activities of PTSD rats were significantly increased. PTSD rats had increased norepinephrine concentration and decreased monoamine oxidase A activity in cerebral cortex. The PTSD-induced elevation of carbonylated proteins and lipid peroxidation products in these organs reflects oxidative stress, a known cause of organ pathology. IHC alleviated PTSD-induced metabolic and structural injury and reduced oxidative stress. Therefore, IHC is a promising preventive treatment for PTSD-related morphological and functional damage to organs, due, in part, to IHC’s reduction of oxidative stress.

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Section: Discussionsupporting

confidence: 87%

Intermittent Hypoxic Conditioning Alleviates Post-Traumatic Stress Disorder-Induced Damage and Dysfunction of Rat Visceral Organs and Brain

Манухина

Tseĭlikman

Karpenko

et al. 2020

IJMS

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“…The comparison of corticosterone and testosterone levels in the blood serum demonstrated that the decrease in measured hormone levels of all rats exposed to stress ( Table 1 ). The reduction of corticosterone level is a generally accepted index of PTSD-like state development [ 6 , 10 , 12 , 13 ]. Nevertheless, the values of corticosterone levels in resistant rats were statistically higher than in sensitive ones ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…The study was conducted in autumn and winter period on mature male Wistar rats ( n = 60) initially weighing 180–200 g. The animals were kept in groups of 10. PTSD was simulated using the generally accepted predator stress model, an evolutionary selective rodent fear of predators and their scent, established by Cohen and Zohar and improved by Tseilikman et al [ 5 , 6 ]. The researches of Voznessenskaya et al.…”

Section: Methodsmentioning

confidence: 99%

New Morphofunctional Criteria for Resistance Profile in Post-Traumatic Stress Disorder Models as Adrenal Dysfunction Trigger

et al. 2021

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For the first time in modeling posttraumatic stress disorder (PTSD), we have described the morphofunctional state of adrenal glands in Wistar rats resistant and sensitive to predator stress (rodent fear of the predator). Despite the evident signs of adrenal dysfunction in both phenotypes, we have discovered the thickening of undifferentiated cell zone and high indices of functional activity of stem cells in resistant animals, suggesting ample adaptation. The most important data demonstrate the direct relationship between the reduction of corticosterone and testosterone levels and adrenal dysfunction in PTSD models. The study results allow considering the adrenal stem cells as potential therapeutic targets.

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“…[15], в которой было изменено количество экспозиций «запаха хищника» (кошачьей мочи) с одного до 10 раз. Животные подвергались стрессу ежедневно в течение 10 мин [16]. Мочевые метки взрослого домашнего кота предъявлялись в чашках Петри, накрытых медицинской марлей, животным группы «ПТСР» и «ПТСР+АПГ».…”

Section: методикаunclassified

Effect of adaptation to intermittent hypoxia on serotonin metabolism and oxidative stress in the hippocampus of rats with experimental post-traumatic stress disorder

Алилуев¹,

Семенова²,

Порядин³

et al. 2021

Zhurnal «Patologicheskaia Fiziologiia I Eksperimental`naia Terapiia»

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Введение. Посттравматическое стрессовое расстройство (ПТСР) формируется спустя длительный срок после переживания психической травмы. Имеются данные о низком уровне серотонина у больных ПТСР, который часто сочетается с окислительным стрессом, обусловленным нейровоспалением. Представляется актуальным поиск эффективных средств немедикаментозной коррекции ПТСР. Одним из высокоэффективных и наиболее широко используемых методов является адаптация к периодической гипоксии (АПГ). Цель работы - исследование влияния АПГ на обмен серотонина и показатели окислительного стресса в гиппокампе животных при экспериментальном ПТСР. Методика. Исследование выполнено на 34 половозрелых самцах крыс Вистар, которые были разделены на 4 группы («Контроль», «ПТСР», «АПГ», «ПТСР+АПГ»). В качестве модели экспериментального ПТСР была использована модель хронического предаторного стресса, где животные подвергались «запаху хищника» (кошачьей мочи) по 10 мин в течение 10 сут. После этого крыс адаптировали к периодической гипоксии в гипобарической барокамере в течение 14 сут, начиная с 30 мин в 1-е сут на симулированной высоте 1000 м, с постепенным увеличением «высоты» и времени экспозиции до 4000 м в течение 4 ч на 5-е сут и в последующие дни. Поведенческие реакции животных изучали при помощи теста «приподнятый крестообразный лабиринт» (ПКЛ). Концентрацию серотонина и его метаболита 5-гидроксииндолуксусной кислоты (5-ГИУК) определяли методом высокоэффективной жидкостной хроматографии. Содержание первичных и вторичных продуктов перекисного окисления липидов (ПОЛ) оценивали спектрофотометрически согласно методике И.А. Волчегорского и соавт. Уровень окислительной деструкции белков оценивали по содержанию карбонилированных белков. Результаты. При тестировании в ПКЛ было установлено, что у животных через 14 сут после завершения предаторного стресса по сравнению с контролем наблюдалось усиление тревожности, которое ограничивалось курсом АПГ. Одновременно с этим установлено снижение содержания серотонина и повышение уровня 5-ГИУК, что привело к существенному повышению метаболического индекса серотонина. Курс АПГ не привел к статистически значимым изменениям содержания серотонина и его метаболита по сравнению с контролем. В группе «ПТСР+АПГ» по сравнению с группой «ПТСР» отмечено повышение концентрации серотонина при одновременном снижении 5-ГИУК и метаболического индекса серотонина. Исследование окислительного стресса в гиппокампе животных с ПТСР-подобным состоянием показало повышение базального уровня карбонилированных белков по сравнению с контролем и увеличение содержания вторичных продуктов ПОЛ. Заключение. При экспериментальном ПТСР в гиппокампе снижение содержания серотонина ассоциировано с усилением его метаболизма, что сопровождается усилением окислительного стресса. Нейропротекторное действие АПГ выражается в нивелировании окислительного стресса в гиппокампе. Background. Post-traumatic stress disorder (PTSD) develops long after a mental traumatic event. In patients with PTSD, low serotonin levels often combine with oxidative stress-induced inflammation. Searching for effective non-pharmacological therapies for PTSD is important. Adaptation to intermittent hypoxia (AIH) is one of highly effective and widely used methods. The aim of this study was to elucidate the effect of AIH on serotonin metabolism and oxidative stress in the hippocampus of rats with PTSD. Methods. The study was performed on 34 sexually mature male Wistar rats divided into 4 groups: control, PTSD, AIH, and PTSD+AIH. Experimental PTSD was modeled with chronic predator stress, where animals were exposed to predator smell (cat urine) for 10 days, 10 min daily. Then rats were conditioned in a hypobaric altitude chamber for 14 days at a 1,000-m simulated altitude for 30 min on day 1 with altitude and duration progressively increasing to 4,000 m for 4 h on day 5 and all the remaining days. Behavioral reactions of rats were studied with the elevated plus maze (EPM) test. Concentrations of serotonin and the serotonin metabolite, 5-hydroxy indole acetic acid (5-HIAA), were measured by high-performance liquid chromatography. Contents of primary and secondary lipid peroxidation (LPO) products were measured spectrophotometrically according to the method of I.A. Volchegorskiy et al. The oxidative damage to proteins was assessed by the content of carbonylated proteins. Results. The EPM test showed that 14 days after the predator stress completion, the anxiety level was higher than in control, and this effect was alleviated by AIH. Also, stress-exposed rats had lower serotonin and higher 5-HIAA concentrations, which resulted in a significantly higher serotonin metabolic index compared to the control. The course of AIH did not cause any significant changes in concentrations of serotonin and its metabolite as compared to the control. In the PTSD + AIH group compared to the PTSD group, the serotonin concentration was increased whereas the 5-HIAA concentration and the metabolic serotonin index were decreased. Studying oxidative stress in the hippocampus of rats with the PTSD-like condition showed that both the basal level of carbonylated proteins and the content of LPO secondary products were increased compared to the control group. Conclusions. In experimental PTSD in the hippocampus, the decrease in serotonin content was associated with the increase in its metabolism and with potentiation of oxidative stress. The neuroprotective effect of AIH was evident as alleviation of oxidative stress in the hippocampus.

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Post-Traumatic Stress Disorder Chronification via Monoaminooxidase and Cortisol Metabolism

Cited by 13 publications

References 26 publications

Intermittent Hypoxic Conditioning Alleviates Post-Traumatic Stress Disorder-Induced Damage and Dysfunction of Rat Visceral Organs and Brain

Intermittent Hypoxic Conditioning Alleviates Post-Traumatic Stress Disorder-Induced Damage and Dysfunction of Rat Visceral Organs and Brain

New Morphofunctional Criteria for Resistance Profile in Post-Traumatic Stress Disorder Models as Adrenal Dysfunction Trigger

Effect of adaptation to intermittent hypoxia on serotonin metabolism and oxidative stress in the hippocampus of rats with experimental post-traumatic stress disorder

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