A new roundup read: Adult hippocampal neurogenesis in major depression and Alzheimer's disease

Depression and dementia are major public health problems

1Can neurogenesis be the link between MDD and AD?

The hippocampus plays a key role

Figure 1.

2 Findings and evidence in human AHN

For decades, it was assumed that none of the neurons in the adult brain were produced

3MDD is associated with changes in AHN

The hippocampus is involved in mood regulation, and changes in neurogenic activity are associated

Postmortem immunohistochemical analysis of human hippocampal tissue in depressed patients showed a decrease in the number of NeuN+ granular neurons (GNS) in the hippocampus, with levels dropping to ~30%.

In the same study, the authors looked at the role

In addition to immunohistochemical analysis, other methods have also been used to study the role of

Several studies have shown that both pharmacological and non-pharmacological interventions may enhance AHN, which not only improves depressive symptoms, but also has a beneficial effect on cognition, which can reduce the risk of

4 AD changes in human neurogenesis

Multiple studies in rodents and humans have shown the role

Tobin et al.

Hippocampal gene expression profiles sequenced for RNA sequencing from young, healthy, and AD patients revealed that differences in gene expression in AD are associated

Based on these findings, another study reported differential methylation

5AHN is a potential vector for increased risk of AD associated with MDD

Given that AHN may change in both MDD and AD, AHN may not only be associated with people with MDD, but may also mediate an increased

A recent study used genome-wide association studies (GWASs) to aggregate mRNA expression analysis of MDD risk genes in AD patients and mouse AD models, as well as sequencing the full coding region of MDD risk genes in 107 Han AD patients

Comparative analysis of neurogenic decrease in 6AD and MDD

The process of AHN involves multiple stages and can be distinguished by the expression of different markers, from radial glial neural stem cells to transiently expanding neural progenitor cells and neuroblasts to immature and mature post-mitosis neurons (Figure 2A

A decrease in NeuN cells does not necessarily mean a decrease in newborn neurons, and an increase in the rate of apoptosis can lead to similar results
.
Only the addition of Nestin as a second marker is more clear, and a reduction in NeuN+ cells may be the result of
a decrease in Nestin NSCs/NPCs.
Co-labeling of DCX with a second marker of post-mitosis cells (NeuN, PSA-NCAM, βIII-tubulin, CB, or PROX1) provides more reliable data to demonstrate a decrease
in neuroblasts and neurons after early mitoticosis.
While this provides evidence of a decrease in neuroblasts and early mitosis cells, it does not provide information
about the NSC pool.
Therefore, none of the above studies have mapped a complete picture
of neurogenic trajectories.
It may be useful to define different sets of tags to label all phases of AHN in order to create comparable findings in different studies
.
In addition, an analysis of all stages of AHN allows for a better understanding of where neurogenesis may be disturbed
.

When observing changes in AHN in MDD, different DG subregions show that MDD-related changes are mainly concentrated in pre- and mid-DG
.
The decrease in neurogenic activity in the anterior region is more significantly consistent with previous studies, suggesting that anterior (mouse ventral) DG is more involved in mood regulation, and posterior (mouse dorsal) DG has a stronger association
with cognition.
In the context of AD, it will be interesting to make similar distinctions across subregions to examine whether posterior DG changes may be more significant

Figure 2.
Staging and immunocytochemistry of adult hippocampal neurogenesis in MDD and AD

7 Summary and Outlook

In our aging population, depression and dementia are becoming increasingly prominent and creating challenges
to society.
Depression as a possible risk factor for dementia and the role of MDD and AD overlap are still controversial
.
Here, we focus on human studies demonstrating the role of AHN in MDD and AD, as well as some evidence that hippocampal neurogenesis may show a convergent link
between these two diseases.

While the use of antidepressants improves cognition in people with Lewy body dementia, this does not necessarily mean that the same applies to AD
.
We recommend further investigation into whether treatment that inhibits or delays cognitive decline and AD involves AHN
.
Postmortem analysis of neurogenic decline in MDD or AD yields findings that are complementary but difficult to compare
.
One way to conduct a more comprehensive study of AHN in depression and dementia is to define a common set of markers that can label all the different stages
of neurogenesis in humans.
This will enable people to compare the results of different studies and diseases and be able to better explain the role of
AHN.
In addition, postmortem tissue analysis describes only one cross-section of ACN, which is a very dynamic process
.
While recent studies have shown a reduction in neurogenesis, it cannot be proven with certainty because not all stages of AHN are visualized in these studies
.
AHN is a dynamic process, and developing a real-time model that directly evaluates AHN helps to understand its role
in MDD and AD.
Some in vitro models of human hippocampal neurogenesis already exist; For example, human-induced pluripotent stem cell-derived GNs
.
Similar models can be used to study the role
of hippocampal neurogenesis in MDD and AD.

Genetics can provide further insight into the overlap
of AD and MDD.
Multiple GWASs studied genetic alterations in MDD or AD and identified overlap
between the two diseases.
Combining these data with cell assays can lead to a better understanding
of the function of AHN as a possible aggregation mechanism.

In summary, AHN is essential
for the performance of new memory and cognitive functions, as well as for the regulation of emotions.
If disturbed, it can have serious consequences
for mental health.
AHN has been shown to be involved in AD pathology and to play a role
in MDD.
The human studies presented in this article provide some evidence that AHN is involved in both diseases
.
Even though the current findings do not prove a direct link between AD and MDD, they suggest that AHN is a possible crossroads
.
In the long run, this opens up a new avenue for potentially preventing the onset of AD and other dementias
.