Immunity system complexity: a functional DNA fragment (Introduction)

by David Turell , Monday, June 10, 2024, 17:18 (166 days ago) @ David Turell

A clever study followed one DNA fragment:

https://www.the-scientist.com/an-immune-mechanism-maintains-memory-71925

"Cooperating neurons form the physical structure of a memory, but how these assemblies form and persist as long-term memories still stumps scientists. After an event, brain activity increases in the hippocampus, which consolidates information and holds short-term memories. However, long-term memories are stored in the cortex, which means that the two regions must be able to communicate.

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"In neurons, both stress and activation lead to double stranded DNA (dsDNA) breaks predominantly in the mitochondria and genome, respectively.2,3 To determine the source of dsDNA, the team isolated and sequenced extranuclear DNA from neurons after fear conditioning and showed that these fragments belonged to genomic DNA. Additionally, immunofluorescent labeling of a histone variant that denotes dsDNA breaks confirmed that these breaks occurred specifically in neurons.

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"One hour after conditioning, the researchers showed that channels formed in the nuclear membrane that permitted the dsDNA fragments to exit the nucleus near the endoplasmic membrane where TLR9 also resides; a small number of these channels remained visible through the 96-hour observation period. The team confirmed by using microscopy that TLR9 and dsDNA fragments associated together. Starting at six hours after fear conditioning, the dsDNA localized near the centrosome, where the team also identified a DNA damage repair enzyme.

"To explore the function of dsDNA breaks and TLR9 activation further, the team generated mice with the TLR9 gene knocked out (TLR9 KO) specifically in neurons using adeno-associated viral delivery of Cre-recombinase. TLR9 KO animals exhibited impaired memory and learning after fear training compared to wild type mice.

"While fear conditioning induced expression in genes related to ER proteins, vesicle transport, and interleukin-6 and TLR9, TLR9 KO animals failed to express these genes. Absence of TLR9 in neurons also reduced the localization of DNA repair proteins and the production of extracellular structures previously shown to be important for memory.

"Jacob Raber, a neuroscientist at the Oregon Health and Science University who was not involved with the study, said that the finding linking the immune system to the formation of memory was striking. “It drives home the idea that you need immune activation,” he said. “If you don't have any, it's not good. If you have too much, it's not good. If it's chronic, it's not good.'”

Comment: such specificity of a fragment of DNA strongly suggests design.