Ataki epileptyczne aktywują białko c-fos w specjalnych komórkach glejowych zwanych fostrocytami, które hamują kolejne ataki
Seizures induce c-fos expression in a subset of astrocytes, termed fostrocytes, that dampen subsequent seizures
W skrócie
[Preprint - wstępne wyniki] Naukowcy odkryli, że podczas ataków epileptycznych w mózgu aktywują się specjalne komórki glejowe zwane fostrocytami, które wykazują długotrwałą ekspresję białka c-fos. Uszkodzenie tych fostrocytów u myszy doświadczalnych prowadziło do zwiększenia częstości ataków, co sugeruje, że komórki te naturalnie chronią przed napływem zapalenia. Wyniki wskazują, że terapie wzmacniające aktywność fostrocytów mogłyby działać przeciw atakom epileptycznym.
Oryginalny abstract (angielski)
Objective: The original goal was to map neuronal circuits activated by spontaneous seizures in models of temporal lobe epilepsy. Studies used the c-fos driven TRAP2 system, which has been used successfully to label neurons after seizures. Unexpectedly, astrocytes were also labeled, then shown to express c-fos in a sustained manner after seizures. The role of these so-called fostrocytes in spontaneous seizures was studied using novel Cre-dependent AAVs. Methods: Studies used a homozygous mouse line produced by crossing TRAP2 Cre-driver mice with the Ai9 Cre-reporter line. Seizures were induced using electrical stimulation, kainic acid, or pilocarpine. Cre-dependent AAVs used the GFAP promoter to drive expression of either the catalytic A chain of diphtheria toxin (DTA), GFP, or empty vector. Spontaneous seizures were continuously recorded using EEG. Results: Discrete seizures in naive mice evoked transient c-fos expression in all astrocytes, while status epilepticus evoked a higher and sustained level of c-fos expression. Timing the activation of the TRAP2 system allowed specific labeling of the subset of astrocytes with high c-fos expression. These cells were colocalized with established astrocyte markers, showed reactive astrocyte morphology, and were selectively labeled by GFAP-driven Cre-dependent AAVs. Ablation of fostrocytes in spontaneously seizing mice increased seizure frequency. Significance: Next-generation sequencing studies have revealed a great diversity of astrocyte subtypes, identifying clusters with up-regulated c-fos expression in patients with neurological disorders. In conclusion, these studies suggest that therapies that augment the activity of c-fos expressing astrocytes would have anti-seizure activity.