S. D. Nikolaeva, L. S. Nikitina, M. V. Glazova, V. T. Bakhteeva, E. V. Chernigovskaya
{"title":"The Functional State of Glutamate- and GABA-Ergic Neurons in the Inferior Colliculi of Krushinsky–Molodkina Rats at Early Stages of Epileptogenesis","authors":"S. D. Nikolaeva, L. S. Nikitina, M. V. Glazova, V. T. Bakhteeva, E. V. Chernigovskaya","doi":"10.1134/s0022093024020212","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Disturbances in the neurotransmitter systems associated with\nthe development of temporal lobe epilepsy (TLE) have been well-studied\nin forebrain structures including the temporal cortex, amygdala, and\nhippocampus. It is known that in rodents genetically prone to audiogenic\nseizures, TLE establishment induced by audiogenic kindling is also\nassociated with the involvement of the forebrain, however, initially\nepileptiform activity arises in the brainstem, in particular, in\nthe inferior colliculi (IC). It is reasonable to suppose that neurochemical\nalterations in the IC may contribute significantly to the spreading\nof epileptiform activity at early steps of TLE development. At the\nsame time, the functional state of the key neurotransmitter systems\nin the IC of audiogenic rodents exposed to audiogenic kindling remains\nunknown. In the present work, we performed a comprehensive analysis\nof proteins involved in glutamate- and GABA-ergic transmission in\nthe IC of Krushinsky–Molodkina (KM) rats genetically prone to audiogenic\nseizures. A modified audiogenic kindling protocol was used to reproduce\nthe early stage of TLE development. According to this protocol,\nrats were exposed to daily audiogenic stimulations for seven days.\nNaive KM rats were used as a control. Although the rodent’s predisposition to\naudiogenic seizures is often associated with the impairment of GABAergic\ntransmission, no significant changes were found in the expression\nof GABA synthesis enzymes and GABA<sub>A</sub> receptor\nα1 subunit in the IC of KM rats either 24 hours or a week after\ntheir last seizure. However, 24 hours after the last audiogenic\nstimulation, an increase in glutamatergic transmission in the IC\nwas observed including upregulation of ERK 1/2 kinases, synaptic\nproteins synapsin 1 and SV2B, VGLUT1 and VGLUT2. One week after\nthe last seizure, only an increase in VGLUT1 content in the IC was\nobserved, suggesting the persistent changes in the neurons of forebrain\nstructures, in particular, of the temporal cortex.</p>","PeriodicalId":15805,"journal":{"name":"Journal of Evolutionary Biochemistry and Physiology","volume":"52 1","pages":""},"PeriodicalIF":0.6000,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Evolutionary Biochemistry and Physiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1134/s0022093024020212","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Disturbances in the neurotransmitter systems associated with
the development of temporal lobe epilepsy (TLE) have been well-studied
in forebrain structures including the temporal cortex, amygdala, and
hippocampus. It is known that in rodents genetically prone to audiogenic
seizures, TLE establishment induced by audiogenic kindling is also
associated with the involvement of the forebrain, however, initially
epileptiform activity arises in the brainstem, in particular, in
the inferior colliculi (IC). It is reasonable to suppose that neurochemical
alterations in the IC may contribute significantly to the spreading
of epileptiform activity at early steps of TLE development. At the
same time, the functional state of the key neurotransmitter systems
in the IC of audiogenic rodents exposed to audiogenic kindling remains
unknown. In the present work, we performed a comprehensive analysis
of proteins involved in glutamate- and GABA-ergic transmission in
the IC of Krushinsky–Molodkina (KM) rats genetically prone to audiogenic
seizures. A modified audiogenic kindling protocol was used to reproduce
the early stage of TLE development. According to this protocol,
rats were exposed to daily audiogenic stimulations for seven days.
Naive KM rats were used as a control. Although the rodent’s predisposition to
audiogenic seizures is often associated with the impairment of GABAergic
transmission, no significant changes were found in the expression
of GABA synthesis enzymes and GABAA receptor
α1 subunit in the IC of KM rats either 24 hours or a week after
their last seizure. However, 24 hours after the last audiogenic
stimulation, an increase in glutamatergic transmission in the IC
was observed including upregulation of ERK 1/2 kinases, synaptic
proteins synapsin 1 and SV2B, VGLUT1 and VGLUT2. One week after
the last seizure, only an increase in VGLUT1 content in the IC was
observed, suggesting the persistent changes in the neurons of forebrain
structures, in particular, of the temporal cortex.
期刊介绍:
Journal of Evolutionary Biochemistry and Physiology publishes original experimental and theoretical and review articles related to evolution of the main forms of metabolism in connection with life origin; comparative and ontogenetic physiology and biochemistry, biochemical evolution of animal world; as well as evolution of functions; morphology, pharmacology, pathophysiology and ecological physiology. The journal welcomes manuscripts from all countries in the English or Russian language.