Comparison of morphofunctional features of the ventral hippocampus in adult and old rats after combined stress

Ekova, Maria; Смирнов, А. В.; Шмидт, М В; Tyurenkov, I. N.; Волотова, Е. В.; Куркин, Д. В.; Grigorieva, N. V.; Ермилов, В В; Медников, Д. С.

doi:10.1134/s2079057016030036

Cited by 4 publications

(5 citation statements)

References 18 publications

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“…Additionally, these findings suggest the absence of sexual dimorphism in SR expression within this particular brain region. Additionally, our findings, revealing a decline in SR expression in the hippocampal subregions with aging, are consistent with previous research indicating a reduction in SR activity in the neuropil of the radial layer of the CA1 field in aged rats exposed to stress [ 58 , 59 ]. This alignment suggests a potential connection between age-related changes in SR expression and stress-induced alterations in hippocampal regions.…”

Section: Discussionsupporting

confidence: 93%

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Serine racemase expression profile in the prefrontal cortex and hippocampal subregions during aging in male and female rats

Bean,

Bose,

Rani

et al. 2024

Aging

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Aging is associated with a decrease in N-methyl-D-aspartate (NMDA) receptor function, which is critical for maintaining synaptic plasticity, learning, and memory. Activation of the NMDA receptor requires binding of the neurotransmitter glutamate and also the presence of co-agonist D-serine at the glycine site. The enzymatic conversion of L-serine to D-serine is facilitated by the enzyme serine racemase (SR). Subsequently, SR plays a pivotal role in regulating NMDA receptor activity, thereby impacting synaptic plasticity and memory processes in the central nervous system. As such, age-related changes in the expression of SR could contribute to decreased NMDA receptor function. However, age-associated changes in SR expression levels in the medial and lateral prefrontal cortex (mPFC, lPFC), and in the dorsal hippocampal subfields, CA1, CA3, and dentate gyrus (DG), have not been thoroughly elucidated. Therefore, the current studies were designed to determine the SR expression profile, including protein levels and mRNA, for these regions in aged and young male and female Fischer-344 rats. Our results demonstrate a significant reduction in SR expression levels in the mPFC and all hippocampal subfields of aged rats compared to young rats. No sex differences were observed in the expression of SR. These findings suggest that the decrease in SR levels may play a role in the age-associated reduction of NMDA receptor function in brain regions crucial for cognitive function and synaptic plasticity.

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Section: Discussionsupporting

confidence: 93%

“…Interestingly, reduced SR expression was found in additional areas of interest including VH and hypothalamus. Our results of decreased SR expression in the VH with aging align with prior findings indicating reduced SR activity in the neuropil of the radial layer of the CA1 field in aged rats exposed to stress [ 58 , 59 ].…”

Section: Introductionsupporting

confidence: 91%

Serine racemase expression profile in the prefrontal cortex and hippocampal subregions during aging in male and female rats

Bean,

Bose,

Rani

et al. 2024

Aging

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“…In the study by Parashar et al, exposure of mice to unpredictable chronic stress was associated with a significant increase in the hippocampal CA3 neurodegeneration [11]. Ekova et al reported dystrophic lesions in the hippocampal CA1 and CA3 neurons in mice exposed to stressful condition [12]. In the case of clinical studies, it has been determined that brain MRI images of patients with depression show changes in hippocampal volume and density of CA1 and CA3 pyramidal neurons [10,50].…”

Section: Discussionmentioning

confidence: 99%

“…Animal studies have also shown that depression induced by exposure to unpredictable chronic stress is associated with a significant increase in the hippocampal CA3 neurodegeneration [11]. Dystrophic lesions of the hippocampal CA3 neurons have been reported in rats with depressive-like behaviors [12].…”

Section: Introductionmentioning

confidence: 99%

Rutin via Increase in the CA3 Diameter of the Hippocampus Exerted Antidepressant-Like Effect in Mouse Model of Maternal Separation Stress: Possible Involvement of NMDA Receptors

Anjomshoa

Boroujeni

Ghasemi

et al. 2020

Behavioural Neurology

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Background and Aim. Rutin is a flavonol with neuroprotective activity. The aim of the present study is to investigate the role of the glutamatergic system in the antidepressant-like effect of rutin in a mouse model of maternal separation (MS) stress focusing on histological changes in the CA3 area of the hippocampus. Methods. Mouse neonates were exposed to MS paradigm 3 hours daily from postnatal days (PND) 2 to 14. The control and MS mice were divided separately into 16 groups (n=8) (8 groups for each set) including mice that received normal saline, mice that received rutin at doses of 10, 50, and 100 mg/kg, mice that received NMDA at a dose of 150 mg/kg, mice that received ketamine (NMDA antagonist) at a dose of 0.25 mg/kg, mice that received NMDA antagonist plus a subeffective dose of rutin, and mice that received NMDA plus an effective dose of rutin. Forced swimming test (FST) was performed. Afterwards, the hippocampus was evaluated in cases of histopathological changes as well as expression of NR2A and NR2B genes. Results. Rutin significantly reduced immobility time in the FST. The expression of NR2A and NR2B subunits of NMDA receptor in MS mice was significantly higher than that in the control group. Rutin significantly decreased the expression of NR2B and NR2A subunits in the hippocampus. The CA3 diameter and percentage of dark neurons in the hippocampus of MS mice significantly decreased and increased, respectively, which partially reversed following rutin administration. Conclusion. Rutin, partially, through a neuroprotective effect on the hippocampus exerted antidepressant-like effect. We concluded that NMDA receptors, at least in part, mediated the beneficial effect of rutin.

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“…В норме уровень глюкокортикоидов регулируется ГГН осью посредством отрицательной обратной связи. Однако в стрессовых ситуациях постоянно высокие концентрации глюкокортикоидов приводят к нарушению регуляции ГГН оси, что вызывает повреждение нейронов гиппокампа, уменьшает уровень нейротрофинов и снижает нейрогенез в зубчатой извилине [4,5]. В зубчатой извилине нейрогенез происходит в субгранулярном слое в течение всей жизни [6,7], вновь образованные клетки перемещаются в гранулярный слой и интегрируются в существующие нейронные цепи, что оказывает положительное влияние на поддержание механизмов адаптации, регуляции настроения и играет важную роль в процессах обучения и памяти, зависящих от гиппокампа [8].…”

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Characteristic of morphological changes in gyrus dentatus at the pharmacological correction of depressive status in adultrats

Смирнов¹,

Ekova²,

Tyurenkov³

et al. 2019

Medical news of the North Caucasus

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1 Волгоградский государственный медицинский университет, Российская федерация 2 Волгоградский медицинский научный центр, Российская федерация characTerisTic oF morPhological changes in gYrus DenTaTus aT The Pharmacological correcTion oF DePressiVe sTaTus in aDulT raTs smirnov a. V. 1, 2 , ekova m. r. 1 , Tyurenkov i. n. 1 , Volotova e. V. 1 1 Volgograd state medical university, russian Federation 2 Volgograd medical research center, russian FederationПри моделировании депрессии у крыс в возрасте 12 месяцев изучены структурные изменения в гранулярном слое зубчатой извилины, установлена возможность фармакологической коррекции выявленных изменений фенибутом и соединениями с лабораторными шифрами ргПУ-189 (салифен -аддукт γ-амино-β-фенилмасляной и салициловой кислот), ргПУ-135 (нейроглутамβ-фенильное производное глутаминовой кислоты). Были сформированы 5 групп по 10 животных в каждой: контрольные крысы; крысы, подвергавшиеся ежедневно в течение 7 суток 30-минутному стрессированию; стрессированные крысы, получавшие фенибут, ргПУ-189, ргПУ-135. Депрессивноподобное состояние вызывали путем моделирования мягкого стрессового воздействия в специальной установке, позволяющей производить комбинирование нескольких стрессорных раздражителей (пульсирующий свет, громкий звук, вибрация). Показано, что после стрессового воздействия у животных в гранулярном слое зубчатой извилины наблюдалось увеличение удельного количества гиперхромных нейронов и удельного количества сморщенных гиперхромных нейронов. Применение соединения ргПУ-189 в большей степени оказывало корректирующее действие, поскольку способствовало снижению как обратимых, так и необратимых изменений в нейронах. Ключевые слова: зубчатая извилина, депрессия, стресс, фенибут, производные глутаминовой кислоты и ГАМК, крысаWhen modeling depression in 12 months age rats, structural changes in the granular layer of dentate gyrus were studied, and the possibility of pharmacological correction of the revealed changes with phenibut and compounds with laboratory codes of RGPU-189 (salifen -adduct of γ-amino-β-phenylbutyric and salicylic acids), RGPU-135 (neuroglutamβ-phenyl derivative of glutamic acid). 5 groups of 10 animals each were formed: control rats; rats subjected to daily 30-minute stress for 7 days; stressed rats treated with phenibut, with RGPU-189, with RGPU-135. Depressive state was caused in animals by simulating mild stress in a special installation, which consists of 6 isolated compartments of the same volume, allowing combining several stressful stimuli (pulsating light, loud sound, vibration). After stress exposure in animals in granular layer of dentate gyrus an increase in specific number of hyperchromatic neurons and specific number of wrinkled hyperchromatic neurons was observed. The use of the compound RGPU-189 to a greater extent had a corrective effect, since it helped to reduce both reversible and irreversible changes in neurons.

show abstract

Comparison of morphofunctional features of the ventral hippocampus in adult and old rats after combined stress

Cited by 4 publications

References 18 publications

Serine racemase expression profile in the prefrontal cortex and hippocampal subregions during aging in male and female rats

Serine racemase expression profile in the prefrontal cortex and hippocampal subregions during aging in male and female rats

Rutin via Increase in the CA3 Diameter of the Hippocampus Exerted Antidepressant-Like Effect in Mouse Model of Maternal Separation Stress: Possible Involvement of NMDA Receptors

Characteristic of morphological changes in gyrus dentatus at the pharmacological correction of depressive status in adultrats

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