Study: How does adult neurogenesis contribute to cognitive function as we age?

New­born neu­ron (green and pur­ple) in brain tis­sue from human epilep­sy patients. Aswathy Ammothumkandy/Bonaguidi Lab/USC Stem Cell, CC BY-SA

Your brain can still make new neu­rons when you’re an adult. But how does the rare birth of these new neu­rons con­tribute to cog­ni­tive function?

Neu­rons are the cells that gov­ern brain func­tion, and you are born with most of the neu­rons you will ever have dur­ing your life­time. While the brain under­goes most of its devel­op­ment dur­ing ear­ly life, spe­cif­ic regions of the brain con­tin­ue to gen­er­ate new neu­rons through­out adult­hood, although at a much low­er rate. Whether this process of neu­ro­ge­n­e­sis actu­al­ly hap­pens in adults and what func­tion it serves in the brain is still a sub­ject of debate among scientists.

Past research has shown that peo­ple with epilep­sy or Alzheimer’s dis­ease and oth­er demen­tias devel­op few­er neu­rons as adults than peo­ple with­out these con­di­tions. How­ev­er, whether the absence of new neu­rons con­tributes to the cog­ni­tive chal­lenges patients with these neu­ro­log­i­cal dis­or­ders face is unknown.

We are part of a team of stem cell researchers, neu­ro­sci­en­tists, neu­rol­o­gists, neu­ro­sur­geons and neu­ropsy­chol­o­gists. Our new­ly pub­lished research reveals that the new neu­rons that form in adults’ brains are linked to how you learn from lis­ten­ing to oth­er people.

The relationship between adult neurogenesis and cognitive function

Researchers know that new neu­rons con­tribute to mem­o­ry and learn­ing in mice. But in humans, the tech­ni­cal chal­lenges of iden­ti­fy­ing and ana­lyz­ing new neu­rons in adult brains, com­bined with their rar­i­ty, had led sci­en­tists to doubt their sig­nif­i­cance to brain function.

To uncov­er the rela­tion­ship between neu­ro­ge­n­e­sis in adults and cog­ni­tive func­tion, we stud­ied patients with drug-resis­tant epilep­sy. These patients under­went cog­ni­tive assess­ments pri­or to and donat­ed brain tis­sue dur­ing sur­gi­cal pro­ce­dures to treat their seizures. To see whether how many new neu­rons a patient had was asso­ci­at­ed with spe­cif­ic cog­ni­tive func­tions, we looked under the micro­scope for mark­ers of neurogenesis.

We found that new neu­rons in the adult brain are linked to reduced cog­ni­tive decline – par­tic­u­lar­ly in ver­bal learn­ing, or learn­ing by lis­ten­ing to others.

This was very sur­pris­ing to us. In mice, new neu­rons are known for their role in help­ing them learn and nav­i­gate new spaces through visu­al explo­ration. How­ev­er, we did not observe a sim­i­lar con­nec­tion between new neu­rons and spa­tial learn­ing in people.

Boosting new neuron production and cognition as we age

Talk­ing with oth­ers and remem­ber­ing those con­ver­sa­tions is an inte­gral part of day-to-day life for many peo­ple. How­ev­er, this cru­cial cog­ni­tive func­tion declines with age, and the effects are more severe with neu­ro­log­i­cal dis­or­ders. As aging pop­u­la­tions grow, the bur­den of cog­ni­tive decline on health care sys­tems world­wide will increase.

Our research sug­gests that the link between new­born neu­rons and ver­bal learn­ing may be foun­da­tion­al to devel­op­ing treat­ments to restore cog­ni­tion in peo­ple. Enhanc­ing new neu­ron gen­er­a­tion could be a poten­tial strat­e­gy to improve brain health and restore cog­ni­tion in aging and in peo­ple with epilep­sy or demen­tia. But for now, these ideas are just goals and any future treat­ments are a long way off.

Impor­tant­ly, our find­ing that new neu­rons func­tion dif­fer­ent­ly in mice and in humans empha­sizes the crit­i­cal need to study bio­log­i­cal func­tions like neu­ro­ge­n­e­sis in peo­ple when­ev­er pos­si­ble. This will ensure that research con­duct­ed in ani­mal mod­els, such as mice, is rel­e­vant to peo­ple and can trans­late to the clinic.

Cur­rent drugs for epilep­sy pri­mar­i­ly aim to reduce seizures, with lim­it­ed focus on address­ing the cog­ni­tive decline patients expe­ri­ence. To enhance cog­ni­tive out­comes for patients, we start­ed a clin­i­cal tri­al focus­ing on boost­ing new neu­ron pro­duc­tion and cog­ni­tion in epilep­sy patients through aer­o­bic exer­cise. We are cur­rent­ly in the ear­ly Phase 1 of the clin­i­cal tri­al, which seeks to estab­lish the safe­ty of the study. Thus far, two patients have suc­cess­ful­ly and safe­ly fin­ished the study. We plan to recruit eight more patients to exer­cise and com­plete this phase.

By bring­ing togeth­er basic sci­ence in the lab and clin­i­cal research in peo­ple, a bet­ter under­stand­ing of brain regen­er­a­tion could help sup­port brain health through­out the lifespan.

– Aswathy Ammoth­umkandy is a Post­doc­tor­al Research Asso­ciate in Stem Cell Biol­o­gy and Regen­er­a­tive Med­i­cine, Charles Liu a Pro­fes­sor of Clin­i­cal Neu­ro­log­i­cal Surgery, and Michael A. Bonagui­di an Asso­ciate Pro­fes­sor of Stem Cell Biol­o­gy and Regen­er­a­tive Med­i­cine; all at the Uni­ver­si­ty of South­ern Cal­i­for­nia. This arti­cle was orig­i­nal­ly pub­lished on The Con­ver­sa­tion.

The Study in Context:

• Study finds con­tin­ued birth of new neu­rons (neu­ro­ge­n­e­sis) well into our 70s 
• Can you grow your hip­pocam­pus? Yes. Here’s how, and why it matters
• What are cog­ni­tive abil­i­ties and how to boost them?