Some memories can be retrieved

Lane Simonian · August 2022

There was a study a few years ago (albeit in mice) that memories were not permanently lost they simply could not be retrieved.

Memories retrieved in mutant ‘Alzheimer’s’ mice

Study suggests that patients with Alzheimer's disease can still form memories, raising hopes of new treatments.

https://www.nature.com/articles/nature.2016.19574

I liken this to a library full of books without call numbers, the books are all still there the patron just has no way of finding them.

Well, this week a new article came out adding to this claim.

Boosting Neuron Formation Restores Memory in Mice With Alzheimer’s Disease

Summary: Increasing neurogenesis by deleting the Bax gene in mouse models of Alzheimer’s improved the animals’ performance in tests measuring spatial recognition and contextual memory.

New neurons are produced from neural stem cells via a process known as neurogenesis. Previous studies have shown that neurogenesis is impaired in both AD patients and laboratory mice carrying genetic mutations linked to AD, particularly in a region of the brain called the hippocampus that is crucial for memory acquisition and retrieval.

https://neurosciencenews.com/bax-alzheimers-neurogenesis-21266/

There is good news and bad news here. Both the regeneration of neurons and increasing levels of acetylcholine (needed for the retrieval of certain forms memories) are possible in Alzheimer's disease. These include memories of places, faces, objects, and repetitive memory (name, numbers, alphabet, etc.).

The bad news is that neurons apparently cannot be generated in other parts of the brain (such as the frontal cortex) that are needed for other forms of memory (in part for example the retrieval of short-term past events).

The pathway by which neurons are regenerated is called the phosphatidyinositol-3 kinase/Akt pathway and it is damaged by nitration (mediated by peroxynitrite) in Alzheimer's disease.

Peroxynitrite induces inactivation of the Akt pathway. Furthermore, overexpression of constitutively active Akt inhibits both peroxynitrite-induced Bax translocation and cell death.

https://pubmed.ncbi.nlm.nih.gov/16410804/

Scavengers of peroxynitrite also denitrate phosphatidyinositol-3 kinase so they help increase neurogenesis and levels of acetylcholine. Panax ginseng (Korean red ginseng) provides may be the best example of this.

Interestingly, Sun ginseng, a kind of dried and heated ginseng, has been shown to enhance neurogenesis in the hippocampus by promoting the activation of Akt and extracellular signal-regulated kinase (ERK) in the hippocampus of mice (Lee et al., 2013), while ginsenoside Rd was found to enhance neurite outgrowth of PC12 cells (Wu et al., 2016) and neurogenesis in cerebral ischemia-induced rat brains (Liu et al., 2015) via activation of Akt and ERK. KRG contains various ginsenosides including Rd and Rg1; therefore, these ginsenosides may play an important role in the increase of KRG-induced neurogenesis through PI3K/Akt and ERK-dependent pathways.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990786/#:~:text=Interestingly%2C%20Sun%20ginseng%2C%20a%20kind,enhance%20neurite%20outgrowth%20of%20PC12

Ginsenosides decrease amyloid β-protein (Aβ) formation by inhibiting β- and γ-secretase activity or by activating the nonamyloidogenic pathway, inhibit acetylcholinesterase activity and Aβ-induced neurotoxicity, and decrease Aβ-induced production of reactive oxygen species and neuroinflammatory reactions. Oral administration of ginsenosides increases the expression levels of enzymes involved in acetylcholine synthesis in the brain and alleviates Aβ-induced cholinergic deficits in AD models.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6190533/

These are the results when you increase neurogenesis and acetylcholine levels in the hippocampus

In the long-term evaluation of the efficacy of KRG after 24 wk, the improved MMSE score remained without significant decline at the 48th and 96th wk. ADAS-cog showed similar findings. Maximum improvement was found around week 24. In conclusion, the effect of KRG on cognitive functions was sustained for 2 yr follow-up, indicating feasible efficacies of long-term follow-up for Alzheimer’s disease.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659550/

Use of panax ginseng can cause stomach upset, jitters, and at least a short-term increase in blood pressure.