Publikationsdatenbank

Neurogenesis in infection-induced epilepsy (2023)

Art

Poster

Autoren

Pauletti, Alberto (WE 14)

Gurlo, P. (WE 14)

Bröer, Sonja (WE 14)

Kongress

35th International Epilepsy Congress

Dublin, Ireland, 02. – 06.09.2023

Quelle

Verweise

URL (Volltext): https://www.ilae.org/files/dmfile/iec-2023-abstract-book-for-website-11.8.23.pdf

Kontakt

Institut für Pharmakologie und Toxikologie

Koserstr. 20
14195 Berlin
+49 30 838 53221
pharmakologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Purpose:
The birth of new neurons (neurogenesis) occurs in distinct brain regions such as the subgranular zone of the dentate gyrus throughout adulthood until senescence. Data from experimental models of epilepsy indicate that seizures acutely increase neurogenesis, however cell proliferation may not result in regeneration because cells born during seizures display morphological and functional alterations, which can induce hyperexcitability. There are no data on neurogenesis of infection-induced epilepsy yet, although infections of the CNS are one of the main causes of epilepsy. Controlling neurogenesis after an infection could constitute a promising therapeutic target.

Method:
We performed an in-depth characterization of time course and fate of neurogenesis in a model of virus-induced seizures (Theiler’s Murine Encephalomyelitis Virus). At 3-, 7-, 14- and 90-days post infection (dpi) C57BL/6 mice were euthanized, and their brains sectioned for immunohistochemical analyses of neurogenesis.

Results:
At 3-14 dpi we found cell proliferation within the dentate gyrus to be significantly increased in infected mice. The amount of proliferation was correlated to the temporal proximity of the last seizure. In order to determine the cell fate, we compared the number of newborn neurons, which did not differ
significantly between seizing and non-seizing or even mock-infected mice. However, mice with seizures displayed aberrant migration of immature neurons. Moreover, close seizure proximity was also linked to the number of glia progenitors. Seizure severity did not have an impact on proliferation of neurons or glia.

Conclusion:
The larger number of cells entering the cell cycle after seizures, as well as their changed migration behavior could contribute to abnormal bursting and self-recurrent seizures. Another mechanism for a pro-epileptogenic influence is differentiation into glia, which contribute to inflammation and disease progression. Further experiments will evaluate whether aberrant neurogenesis can be inhibited, and instead regenerative neurogenesis can be promoted to prevent seizures in infection-induced epilepsy.