Audiogenic kindling stimulates aberrant neurogenesis, synaptopodin expression, and mossy fiber sprouting in the hippocampus of rats genetically prone to audiogenic seizures. 2021

Alexey A Kulikov, and Alexandra A Naumova, and Ekaterina P Aleksandrova, and Margarita V Glazova, and Elena V Chernigovskaya
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 44 Thorez pr., 194223 St. Petersburg, Russia.

Temporal lobe epilepsy is associated with considerable structural changes in the hippocampus. Pharmacological and electrical models of temporal lobe epilepsy in animals strongly suggest that hippocampal reorganization is based on seizure-stimulated aberrant neurogenesis but the data are often controversial and hard to interpret. The aim of the present study was to estimate neurogenesis and synaptic remodeling in the hippocampus of Krushinsky-Molodkina (KM) rats genetically prone to audiogenic seizures (AGS). In our experiments we exposed KM rats to audiogenic kindling of different durations (4, 14, and 21 AGS) to model different stages of epilepsy development. Naïve KM rats were used as a control. Our results showed that even 4 AGS stimulated proliferation in the subgranular layer of the dentate gyrus (DG) accompanied with increase in number of doublecortin (DCX)-positive immature granular cells. Elevated number of proliferating cells was also observed in the hilus indicating the enhancement of abnormal migration of neural progenitors. In contrast to the DG, all DCX-positive cells in the hilus expressed VGLUT1/2 and their number was increased indicating that seizure activity accelerates glutamatergic differentiation of ectopic hilar cells. 14-day kindling further stimulated proliferation, abnormal migration, and glutamatergic differentiation of new neurons both in the DG granular and subgranular layers and in the hilus. However, after 21 AGS increased proliferation was observed only in the DG, while the numbers of immature neurons expressed VGLUT1/2 were still enhanced in both hippocampal areas. Audiogenic kindling also stimulated sprouting of mossy fibers and enhanced expression of synaptopodin in the hippocampus indicating generation of new synaptic contacts between granular cells, mossy cells, and CA3 pyramid neurons. Thus, our data suggest that epilepsy progression is associated with exacerbation of aberrant neurogenesis and reorganization of hippocampal neural circuits that contribute to the enhancement and spreading of epileptiform activity.

UI MeSH Term Description Entries
D007696 Kindling, Neurologic The repeated weak excitation of brain structures, that progressively increases sensitivity to the same stimulation. Over time, this can lower the threshold required to trigger seizures. Kindlings, Neurologic,Neurologic Kindling,Neurologic Kindlings
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012640 Seizures Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder." Absence Seizure,Absence Seizures,Atonic Absence Seizure,Atonic Seizure,Clonic Seizure,Complex Partial Seizure,Convulsion,Convulsions,Convulsive Seizure,Convulsive Seizures,Epileptic Seizure,Epileptic Seizures,Generalized Absence Seizure,Generalized Tonic-Clonic Seizures,Jacksonian Seizure,Myoclonic Seizure,Non-Epileptic Seizure,Nonepileptic Seizure,Partial Seizure,Seizure,Seizures, Convulsive,Seizures, Focal,Seizures, Generalized,Seizures, Motor,Seizures, Sensory,Tonic Clonic Seizure,Tonic Seizure,Tonic-Clonic Seizure,Atonic Absence Seizures,Atonic Seizures,Clonic Seizures,Complex Partial Seizures,Convulsion, Non-Epileptic,Generalized Absence Seizures,Myoclonic Seizures,Non-Epileptic Seizures,Nonepileptic Seizures,Partial Seizures,Petit Mal Convulsion,Seizures, Auditory,Seizures, Clonic,Seizures, Epileptic,Seizures, Gustatory,Seizures, Olfactory,Seizures, Somatosensory,Seizures, Tonic,Seizures, Tonic-Clonic,Seizures, Vertiginous,Seizures, Vestibular,Seizures, Visual,Single Seizure,Tonic Seizures,Tonic-Clonic Seizures,Absence Seizure, Atonic,Absence Seizure, Generalized,Absence Seizures, Atonic,Absence Seizures, Generalized,Auditory Seizure,Auditory Seizures,Clonic Seizure, Tonic,Clonic Seizures, Tonic,Convulsion, Non Epileptic,Convulsion, Petit Mal,Convulsions, Non-Epileptic,Focal Seizure,Focal Seizures,Generalized Seizure,Generalized Seizures,Generalized Tonic Clonic Seizures,Generalized Tonic-Clonic Seizure,Gustatory Seizure,Gustatory Seizures,Motor Seizure,Motor Seizures,Non Epileptic Seizure,Non Epileptic Seizures,Non-Epileptic Convulsion,Non-Epileptic Convulsions,Olfactory Seizure,Olfactory Seizures,Partial Seizure, Complex,Partial Seizures, Complex,Seizure, Absence,Seizure, Atonic,Seizure, Atonic Absence,Seizure, Auditory,Seizure, Clonic,Seizure, Complex Partial,Seizure, Convulsive,Seizure, Epileptic,Seizure, Focal,Seizure, Generalized,Seizure, Generalized Absence,Seizure, Generalized Tonic-Clonic,Seizure, Gustatory,Seizure, Jacksonian,Seizure, Motor,Seizure, Myoclonic,Seizure, Non-Epileptic,Seizure, Nonepileptic,Seizure, Olfactory,Seizure, Partial,Seizure, Sensory,Seizure, Single,Seizure, Somatosensory,Seizure, Tonic,Seizure, Tonic Clonic,Seizure, Tonic-Clonic,Seizure, Vertiginous,Seizure, Vestibular,Seizure, Visual,Seizures, Generalized Tonic-Clonic,Seizures, Nonepileptic,Sensory Seizure,Sensory Seizures,Single Seizures,Somatosensory Seizure,Somatosensory Seizures,Tonic Clonic Seizures,Tonic-Clonic Seizure, Generalized,Tonic-Clonic Seizures, Generalized,Vertiginous Seizure,Vertiginous Seizures,Vestibular Seizure,Vestibular Seizures,Visual Seizure,Visual Seizures
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D055495 Neurogenesis Formation of NEURONS which involves the differentiation and division of STEM CELLS in which one or both of the daughter cells become neurons. Neurogeneses
D019599 Mossy Fibers, Hippocampal Axons of certain cells in the DENTATE GYRUS. They project to the polymorphic layer of the dentate gyrus and to the proximal dendrites of PYRAMIDAL CELLS of the HIPPOCAMPUS. These mossy fibers should not be confused with mossy fibers that are cerebellar afferents (see NERVE FIBERS). Hippocampal Mossy Fibers,Hippocampal Mossy Fiber,Mossy Fiber, Hippocampal
D020195 Epilepsy, Reflex A subtype of epilepsy characterized by seizures that are consistently provoked by a certain specific stimulus. Auditory, visual, and somatosensory stimuli as well as the acts of writing, reading, eating, and decision making are examples of events or activities that may induce seizure activity in affected individuals. (From Neurol Clin 1994 Feb;12(1):57-8) Reflex Epilepsy,Reflex Epilepsy, Audiogenic,Reflex Epilepsy, Cursive (Running),Reflex Epilepsy, Eating-Induced,Reflex Epilepsy, Musicogenic,Reflex Epilepsy, Photosensitive,Reflex Epilepsy, Reading,Audiogenic Epilepsy,Cursive Epilepsy,Decision Making Reflex Epilepsy,Eating-Induced Epilepsy,Epilepsy, Photogenic,Epilepsy, Reading,Immersion Related Epilepsy,Musicogenic Epilepsy,Photosensitive Epilepsy,Reading Epilepsy,Reflex Epilepsy, Visual Pattern,Tactile Reflex Epilepsy,Visual Pattern Reflex Epilepsy,Writing-Induced Reflex Epilepsy,Audiogenic Epilepsies,Audiogenic Reflex Epilepsies,Audiogenic Reflex Epilepsy,Cursive Reflex Epilepsies (Running),Cursive Reflex Epilepsy (Running),Eating Induced Epilepsy,Eating-Induced Epilepsies,Eating-Induced Reflex Epilepsies,Eating-Induced Reflex Epilepsy,Epilepsies, Audiogenic Reflex,Epilepsies, Cursive,Epilepsies, Eating-Induced,Epilepsies, Eating-Induced Reflex,Epilepsies, Immersion Related,Epilepsies, Musicogenic,Epilepsies, Musicogenic Reflex,Epilepsies, Photosensitive,Epilepsies, Photosensitive Reflex,Epilepsies, Reading,Epilepsies, Reading Reflex,Epilepsies, Reflex,Epilepsies, Tactile Reflex,Epilepsies, Writing-Induced Reflex,Epilepsy, Audiogenic,Epilepsy, Audiogenic Reflex,Epilepsy, Cursive,Epilepsy, Cursive Reflex (Running),Epilepsy, Eating-Induced,Epilepsy, Eating-Induced Reflex,Epilepsy, Immersion Related,Epilepsy, Musicogenic,Epilepsy, Musicogenic Reflex,Epilepsy, Photosensitive,Epilepsy, Photosensitive Reflex,Epilepsy, Reading Reflex,Epilepsy, Tactile Reflex,Epilepsy, Writing-Induced Reflex,Immersion Related Epilepsies,Musicogenic Epilepsies,Musicogenic Reflex Epilepsies,Musicogenic Reflex Epilepsy,Photosensitive Epilepsies,Photosensitive Reflex Epilepsies,Photosensitive Reflex Epilepsy,Reading Epilepsies,Reading Reflex Epilepsies,Reading Reflex Epilepsy,Reflex Epilepsies,Reflex Epilepsies, Audiogenic,Reflex Epilepsies, Cursive (Running),Reflex Epilepsies, Eating-Induced,Reflex Epilepsies, Musicogenic,Reflex Epilepsies, Photosensitive,Reflex Epilepsies, Reading,Reflex Epilepsies, Tactile,Reflex Epilepsies, Writing-Induced,Reflex Epilepsy, Eating Induced,Reflex Epilepsy, Tactile,Reflex Epilepsy, Writing-Induced,Tactile Reflex Epilepsies,Writing Induced Reflex Epilepsy,Writing-Induced Reflex Epilepsies

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