Introducing the brain: neurons mature slowly (Introduction)

by David Turell , Wednesday, June 05, 2024, 17:39 (169 days ago) @ David Turell

There are controls in the speed of maturation:

https://www.the-scientist.com/human-neurons-play-the-waiting-game-71900?utm_campaign=TS...

"Cellular maturation involves transcriptional, metabolic, and physiological changes that drive cell function. In human neurons, this process takes longer than in most other cell types, lasting almost two decades for some neuronal cells.1 One hypothesis suggests that this extended maturation contributes to the unique features of the human brain.

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"...in a paper published in Nature, a team at Memorial Sloan Kettering Cancer Center showed that an epigenetic mechanism controls maturation of human neurons by acting as a transcriptional barrier.3 Learning these processes in brain development could improve models and open opportunities to study brain disorders.

"Gabriele Ciceri, a study author and developmental biologist at Memorial Sloan Kettering Cancer Center, and his colleagues investigated the underlying mechanisms of neuronal maturation in human neurons. “This pace that is characterized in the different species in vivo is maintained in in vitro models, which suggests that perhaps there is an intrinsic component, so a clock like mechanism that tells the cells at which speed they need to undergo a certain process,” he said.

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"With these synchronized neuron cultures, the team observed their gradual maturity over 100 days by monitoring the development of synapses, cell length, and electrical properties. By using RNA sequencing and assay for transposase- accessible chromatin (ATAC) sequencing, they showed that genes with roles in neuron excitability and connectivity as well as metabolic and immunologic processes activate in a progressive manner.

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"Because EZH2 modifies DNA-bound histones with the addition of methyl groups, the researchers investigated distinct histone modifications in precursor and neuron cells throughout maturation and their relationships with maturation transcription. In precursor cells, some genes involved in synapses exhibited both inhibitory and active histone patterns, indicating genes that were in poised states. Other genes coincided with inhibitory epigenetic signatures at earlier time points, but later in maturation, associated with histone modifications that marked active transcription. Inhibiting EZH2 reduced the presence of inhibitory modifications in early neurons.

"In addition to directly modulating maturation gene expression, the team showed that genes for other chromatin regulators exist in poised states in precursor neurons maintained by an EZH2-dependent inhibitory histone modification. Normal neuron maturation or EZH2 inhibition resulted in the activation of these regulators, which contributed to cellular development. “We were somehow releasing this brake and allowing all those maturation genes to be expressed at a faster pace,” Ciceri said.

"Vanderhaeghen, who was not involved in the study, found the data showing the influence of chromatin regulators on the rate of neuronal maturation convincing. However, he is interested in learning how other factors, such as metabolism, interact with this observed barrier.6 “If you think of this as a clock, is this one clock or various clocks that interact with one another?” he asked."

Comment: this explains why the brain does not fully mature until a person is 25 years old. The newborn receives information constantly and synapse plasticity is in action creating appropriate synapse action levels as synapses mature.