Fight Aging!

One of the many factors impeding the pace of research into age-related neurodegeneration is that it is relatively challenging to obtain human brain tissue from any sizable living population for study. Post-mortem tissue is more accessible, albeit burdened by the usual regulation, but this represents only a slice of the population, largely those with the most advanced burden of damage and dysfunction. By necessity, researchers wanting to investigate earlier stages of degeneration, or healthy brains, are steered towards patients who must undergo forms of brain surgery, and there are always questions as to the degree to which those patients are reflective of the broader population.

In today's open access paper, researchers work with brain tissue derived from epilepsy patients who underwent brain surgery in an attempt to reduce the severity of their condition. Their argument is that this population can provide insight into features of cognitive aging, even though that cognitive aging is accelerated in epileptic patients versus non-epileptic individuals. The study is of interest for the reported correlation between a population of supporting cells in the brain and the severity of cognitive decline. The paper has little to say about the exact mechanisms involved: that is for others to follow up on given the direction provided here.

An age-related decline in human fluid intelligence corresponds with immature astroglia prevalence

Therapeutic development for cognitive decline has been steered by the interpretation that it predominantly results from compromised neuronal function, yet neuron-focused strategies have so far yielded only modest benefits. With the advent of cell type-directed combination therapies targeting both neurons and glia identifying specific cellular drivers of discrete cognitive deficits can guide the design of more effective treatment strategies. Rodent studies have recognized that astroglial cells, traditionally viewed as mere supportive cells to neurons, are active regulators of learning and memory. Meanwhile, various studies indicate that dysfunctional astrocytes contribute to the decline of rodent cognitive functions.

Cognitive decline is a comorbidity that occurs progressively in epilepsy patients. People with epilepsy demonstrate accelerated brain aging and cognitive decline is especially pronounced in older individuals. Mesial Temporal Lobe Epilepsy (MTLE) is the most common form of adult epilepsy, and patients who do not respond to medications undergo surgical removal of epileptic hippocampal tissue as treatment. Since these patients have detailed presurgical cognitive assessment, this platform provides a unique ante-mortem window into understanding the altered cellular features that are associated with human cognitive decline.

Our previous research in MTLE patients revealed the persistent presence of a pathological Dcx+ immature astroglial cell in the epileptic hippocampus that was undetectable in control postmortem tissue. The number of Dcx+ immature astroglial cells in MTLE hippocampus trended toward an increase with age; however, the significance of this phenotype and its association with cognitive decline was not investigated. In this study, we first identified cognitive functions that strongly undergo an age-associated decline in epilepsy patients. We then assessed the significance of an age-associated increase in Dcx+ immature astroglia and how it is associated with various cognitive functions. Our study identified an association between aging, a decline in fluid intelligence and an increase of immature astroglia in epilepsy patients. These findings highlight immature astroglia as an epilepsy-associated cellular feature corresponding to age-related cognitive decline and provides a basis for future mechanistic and translational studies.