Effect of Antibodies to Glutamate on the Content of Neurotransmitter Amino Acids in Brain Structures of Rats with Ischemic Damage to the Prefrontal Cortex

2012 ◽  
Vol 153 (1) ◽  
pp. 13-15
Author(s):  
G. A. Romanova ◽  
Yu. N. Kvashennikova ◽  
F. M. Shakova ◽  
T. V. Davydova
Keyword(s):  
Amino Acids ◽  
Prefrontal Cortex ◽  
Brain Structures ◽  
Ischemic Damage ◽  
Neurotransmitter Amino Acids ◽  
Antibodies To Glutamate

Neuroprotective effects of glutamate antibodies on memory impairment induced by proinflamatory S100A9 protein oligomers in aging animals

2017 ◽  
pp. 13-20
Author(s):  
М.А. Грудень ◽  
Т.В. Давыдова ◽  
В.С. Кудрин ◽  
В.Б. Наркевич ◽  
Л.А. Ветрилэ ◽  
...  
Keyword(s):  
Amino Acids ◽  
Prefrontal Cortex ◽  
Biogenic Amines ◽  
Memory Trace ◽  
Brain Structures ◽  
Behavioral Experiments ◽  
Neuroprotective Effects ◽  
Neurotransmitter Amino Acids ◽  
Memory Disorder

Цель исследования - изучение эффектов хронического интраназального введения антител к глутамату совместно с полученными in vitro олигомерами провоспалительного белка S100A9 на процесс воспроизведения пространственной памяти, а также на содержание нейромедиаторных аминокислот и биогенных аминов в релевантных структурах мозга - гиппокампе и префронтальной коре у 12-месячных мышей С57Bl/6. Методика. В поведенческих экспериментах у всех животных проводили выработку условного рефлекса пассивного избегания и тестировали воспроизведение памятного следа, после этого в нейрохимическом исследовании в гиппокампе и префронтальной коре методом ВЖХ проводили определение концентрации нейромедиаторных аминокислот и биогенных аминов. Результаты. Показано, что введение белка S100A9 олигомеров индивидуально приводило к нарушению воспроизведения памятного следа, а в сочетании с антителами к глутамату данного эффекта выявлено не было. Обнаружено значительное повышение концентрации глутамата в обеих церебральных структурах стареющих животных при действии S100A9 олигомеров и снижение содержания аминокислоты при совместном введении с антителами к глутамату до нормы. Показано существенное снижение содержания дофамина в гиппокампе и префронтальной коре в условиях влияния S100A9 олигомеров, а также повышение уровня его метаболитов в гиппокампе с нормализацией обмена дофамина в присутствии антелел к глутамату. Заключение. Выявленные антиамнестические эффекты антител к глутамату и нормализация нейрохимического профиля в условиях вызванной центральной токсичностью S100A9 олигомерами могут быть использованы в разработке подходов нейропротективной коррекции в том числе при болезни Альцгеймера. The aim of this study was to investigate effects of chronic intranasal administration of glutamate antibodies with in vitro -generated proinflammatory S100A9 protein oligomers, on spatial memory of 12-month old C57Bl/6 mice. In addition, the brain content of neurotransmitter amino acids and biogenic amines was monitored in memory-relevant brain structures (hippocampus and prefrontal cortex) of these animals. Methods. In behavioral experiments, all animals were conditioned in a passive avoidance reflex test and the memory trace was evaluated. In a simultaneous neurochemical study, HPLC-electrochemical detection analysis was performed to measure concentrations of neurotransmitter amino acids and biogenic amines in the hippocampus and prefrontal cortex. Results. Administration of S100A9 oligomers alone resulted in disruption of the memory trace retrieval whereas their combination with glutamate antibodies abolished this memory disorder. Significant increases in glutamate concentration were observed in both of the cerebral structures of ageing animals in response to S100A9 oligomers alone, and there was a reduction of the amino acid levels when coadministered with glutamate antibodies. S100A9 oligomers also evoked a decrease in hippocampal and prefrontal cortical dopamine and synchronously elevated dopamine metabolite concentrations, both of these actions being normalized by glutamate antibody coadministration. Conclusion. Disclosure of the antiamnesic effects of glutamate antibodies, along with their neurochemical stabilizing activity to S100A9 oligomer neurotoxicity might be utilized in the development of neuroprotective approaches in Alzheimer’s disease.

scholarly journals Glia Not Neurons: Uncovering Brain Dysmaturation in a Rat Model of Alzheimer’s Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 823
Author(s):  
Ekaterina A. Rudnitskaya ◽  
Tatiana A. Kozlova ◽  
Alena O. Burnyasheva ◽  
Natalia A. Stefanova ◽  
Nataliya G. Kolosova
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Prefrontal Cortex ◽  
Brain Structures ◽  
Time Frame ◽  
Oxys Rats ◽  
Unknown Etiology ◽  
Suitable Model ◽  
Model Of Alzheimer’S Disease ◽  
The Brain

Sporadic Alzheimer’s disease (AD) is a severe disorder of unknown etiology with no definite time frame of onset. Recent studies suggest that middle age is a critical period for the relevant pathological processes of AD. Nonetheless, sufficient data have accumulated supporting the hypothesis of “neurodevelopmental origin of neurodegenerative disorders”: prerequisites for neurodegeneration may occur during early brain development. Therefore, we investigated the development of the most AD-affected brain structures (hippocampus and prefrontal cortex) using an immunohistochemical approach in senescence-accelerated OXYS rats, which are considered a suitable model of the most common—sporadic—type of AD. We noticed an additional peak of neurogenesis, which coincides in time with the peak of apoptosis in the hippocampus of OXYS rats on postnatal day three. Besides, we showed signs of delayed migration of neurons to the prefrontal cortex as well as disturbances in astrocytic and microglial support of the hippocampus and prefrontal cortex during the first postnatal week. Altogether, our results point to dysmaturation during early development of the brain—especially insufficient glial support—as a possible “first hit” leading to neurodegenerative processes and AD pathology manifestation later in life.

Pathology, Phenomenology and the Dopamine Hypothesis of Schizophrenia

1987 ◽  
Vol 151 (3) ◽  
pp. 288-301 ◽  
Author(s):  
P. J. McKenna
Keyword(s):  
Prefrontal Cortex ◽  
Basal Ganglia ◽  
Functional Role ◽  
Ventral Striatum ◽  
Brain Structures ◽  
Schizophrenic Symptom ◽  
Dopamine Hypothesis ◽  
Dopamine Innervation

The dopamine hypothesis of schizophrenia implies that positive schizophrenic symptoms should be understandable by reference to brain structures receiving a dopamine innervation, or in terms of the functional role of dopamine itself. The basal ganglia, ventral striatum, septo-hippocampal system, and prefrontal cortex, sites of mesotelencephalic dopamine innervation, are examined and it is argued that their dysfunction could form the basis of particular schizophrenic symptom classes. The postulated involvement of dopamine in reinforcement processes might further assist such interpretations. This type of analysis can be extended to other categories of schizophrenic psychopathology.

High affinity uptake of neurotransmitter amino acids (reply)

Nature ◽  
1975 ◽  
Vol 253 (5491) ◽  
pp. 481-482 ◽  
Author(s):  
LEVI ◽  
RAITERI
Keyword(s):  
Amino Acids ◽  
Neurotransmitter Amino Acids ◽  
High Affinity ◽  
High Affinity Uptake

Abstract WP154: The Role of Ethylmethylhydroxypyridine Succinate in the Induction of PGC-1α in Experimental Ischemic Damage of the Prefrontal Cortex

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Fatima Shakova ◽  
Yuliya Kirova ◽  
Elita Germanova ◽  
Galina Romanova
Keyword(s):  
Prefrontal Cortex ◽  
Antioxidant Defense System ◽  
Peroxisome Proliferator ◽  
Ischemic Damage ◽  
Infarct Zone ◽  
Respiratory Enzymes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Expression Levels ◽  
Ethylmethylhydroxypyridine Succinate ◽  
Intact Rats

The aim of the study was to identify the potential succinate/SUCNR1-mediated mechanism of induction and activation of transcription coactivator PGC-1α (peroxisome proliferator-activated receptor-gamma coactivator 1 alpha) – key activator of the mitochondriogenesis, angiogenesis, fusion of mitochondria, antioxidant defense system that are basis of neuroprotective mechanisms – in the peri-infarction zone of the rat prefrontal cortex (PFC). Focal bilateral damage of the PFC was modeled by photo-induced thrombosis. Ethylmethylhydroxypyridine succinate (a form of succinate passing through the blood-brain barrier; trade name of the drug Mexidol) was injected intraperitoneally 2 hours after infarction and then every day at a dose of 100 mg/kg (7 day course). The tissue of the peri-infarction zone was taken 1, 3, 7 days after the start of therapy, as well as 14 days after discontinuation of the drug. Brain samples were stored in liquid nitrogen, a cytosolic extract was obtained, expression levels of SUCNR1, PGC-1α, transcription factors (NRF1, TFAM), VEGF, catalytic subunits of mitochondrial respiratory enzymes (NDUFV2, SDHA, cyt c1, COX2) and ATP synthases (ATP5A) were determined by Western blot analysis. The study showed that the content of PGC-1α in the peri-infarct zone decreased one day after the induction of ischemic damage by 40% and remained reduced for 21 days after a ischemia. The course of injection of mexidol stabilized PGC-1α in the peri-ischemic zone at a level comparable to the control, both at the stage of treatment and drug withdrawal, and in intact rats induced PGC-1α by 30%. Induction of NRF1, TFAM, NDUFV2, SDHA, cyt c1, ATP5A, indicating the activation of PGC-1α, was observed in rats of the three compared groups, however, the highest expression levels were found in animals subjected to the course of mexidol. Also it was revealed overexpression of SUCNR1 and VEGF in ischemic and intact rats, were injected with mexidol. The study demonstrates for the first time that succinate/SUCNR1 signaling is involved not only in the mechanisms of cerebral angiogenesis, but also in the mechanisms of PGC-1α-dependent neuroprotection. The study opens up new perspectives for pharmacological modulation of PGC-1α levels in the ischemic brain.

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