The reason why some complex behaviors such as cultural learning, self-awareness, and symbolic thought can develop is that human brain neuronal is complex. The human brain is composed of about 100 billion neurons. The total number of synapses in the human neocortex is estimated to be 0.15 quadrillion, and a typical neuron has approximately 5,000-200,000 synapses. Such complexity is the result of millions of years of evolution. For example, the level of complexity in mice and chimpanzees' brains is considered lower than in humans, although they also have high levels of cellular heterogeneity. The mouse brain contains approximately 75 million neurons.
Origins of Neuronal Diversity
-
LINE-1 Retrotransposition
The finding that LINE-1 retrotransposons (L1s) can affect neuronal genomes challenges the dogma that neurons are genetically homogeneous units. L1s are among the most ancient and successful elements in eukaryotic genomes, comprising approximately 20% of mammalian genomes. Most RNA molecules can be subject to retro transposition if hijacked by L1 machinery. Thus, each developing neuron can potentially carry L1-mediated events and, if part of the resultant insertions occurs in genes expressed during neuronal development, it is possible that brain development could be significantly affected by L1s.
The L1 RNA assembles with its own encoded proteins and moves back to the nucleus, where the endonuclease makes a single-stranded nick and the RT uses the nicked DNA to prime reverse transcription from the 3’ end of the L1 RNA. Moreover, the L1-encoded proteins can function in trans to mobilize non-autonomous retrotransposons (such as Alu elements) and cellular messenger RNAs, generating processed pseudogenes. L1s are probably silenced in neural stem cells due to SOX2-mediated transcription repression. Downregulation of SOX2 accompanies chromatin modifications, such as DNA demethylation and histone acetylation, which, in turn, might trigger neuronal differentiation.
Aneuploidy is the loss or gain of chromosomes to produce a numerical deviation from multiples of the haploid chromosomal complement. Such chromosomal alteration has obvious consequences on cellular physiology, leading to well-documented diseases, such as Down’s syndrome. Occasional somatic aneuploidy has frequently been associated with cell death or cancer.
The original observation that aneuploid neural progenitor cells can divide and differentiate in vitro was attributed to a clonal tissue-culture artifact. Chromosomal variation in neurons and glia of the developing and adult mammalian nervous system was mainly detected by fluorescence in situ hybridization (FISH) in brain tissues of rodents and humans. From studies in mice, it is estimated that approximately 33% of neural progenitor cells display chromosomal aneuploidy that encompasses both loss and gain of chromosomes.
The Importance of Understanding Neuronal Complexity in Psychiatric Disorders Research
Depression, anxiety, schizophrenia and other psychiatric disorders are the main causes of disability in the world, and have a huge impact on society. However, despite the obvious need for better treatments and significant progress in understanding the molecular basis of these diseases in recent years, efforts to discover and develop new drugs for the treatment of neuropsychiatric diseases, especially those that may revolutionize the treatment of diseases, have been relatively unsuccessful. This is due to the diversity and complexity of neuronal. Therefore, multidisciplinary approach will be the key to solve this problem.
We have discussed in depth the molecular, cellular and systemic advances related to the discovery of psychotropic drugs. You can choose to browse:
These discussions were used as a basis for proposing measures that could be taken to improve the effectiveness of drug discovery for psychiatric disorders. Creative Biolabs provides comprehensive services to help you improve efficiency and save costs. If you are interested in our services, please contact us.
For Research Use Only.
