Adult born neurogenesis and Epilepsy

What is the main question of this paper

If increasing adult-born neurogenesis protect against the development of chronic epilepsy after status epilepticus

More specifically, does increasing neurogenesis

• reduce severity of status epilepticus

• reduce spontaneous chronic seizures

What is neurogenesis

The formation of new neurons in the hippocampus, specifically in the subgranular zone which matture into granule cells and integrate themselves in the hippocampal cicuits

What can status epilepticus develop

Temporal lobe epilepsy develops after SE. SE can cause

• hippocampal circuit reogranization

• development of spontaneous chornic seizures

What was the genetic model they used in this paper and how did they do this

Nestin-CreERT2 Baxfl/fl mice

• Injected tamoxifen → activates Cre recombinase → cre recombinsae deletes Bax → prevents newborn neurons from dying and increases the survival of adult-born neurons (supports neurogenesis)

What did the authors use to induce seizures in this paper and what was given after to attenuate the severity of ongoing status epilepticus

Pilocarpine = produce temporal lobe epilepsy

Diazepam was given 2 hours after pilocarpine

What did they measure during status epilepticus

1. Duration and severity of first seizure

2. Number of seizures after pilocarpine

3. Duration of SE

What did they measure in chronic epilepsy

• Total seizure number

• Seizure

  • Frequency

  • Duration

  • clustering

• Postictal duration

What did the authors use to confirm and measure the amount of neurogenesis

DCX = marker for immature neurons

What was the two biggest findings of the paper

1. Adult born neurogenesis reduced the DURATION of status epilepticus but it didnt change the number and latency of siezures

2. The beneficial effects were sex specific, female mice showed better improvment and stronger protection

How did neurogenesis reduce chronic seizures

1. Lower frequency

2. reduced seizure clusters

3. fewer days with high seziure counts

What population of cells did the Cre+ female mice show a less loss of and why is this important

Cre+ female mouse models showed less loss of

• mossy cells

• somatostatin internueorn loss

Loss of these cell populations contribute to epileptogenesis

What was an unexpected finding in this paper

Cre+ mice had MORE hilar ectopic granule cells

Past work suggested suppresing neurogenesis reduced seizures because there were fewer hilar ectopic cells. Here was the opposite. This paper suggests that more adult born neuorns coudl coexist with reduced chronic seizures

Epileptogenesis is the process of where a normal brain transfomrs to an epileptic brain, explain what happens in the latency period

Latency period happens after the initial insult causing the transmromaiton

Latency periods: no strokes happen but this is where the brain undergoes molecular and cellular changes

• imabalnce between E/I

• neuronal loss (inhibitory interneurons are lost)

• neuroinflammatory loss

Alters E/I balance and synchronization leading to emergence of chronic epilepsy

Explain etopic migration of adult-born neurons

Normally, neurons are born in the SZ and migrate short distance into the GCL

After seizures, they move to wrong places like the hilus, these are called hilar ectopic granule cells

Because of this misplacement, the ectopic neurons form abnormal connections and creates reuccurent excitatory loops