The role of epigenetic-related codes in neurocomputation: dynamic hardware in the brain

Abstract

This paper presents a review of recent work on the role that two epigeneticrelated systems may play in information processing mechanisms in the brain. The first consists of exosomes that transport epigenetic-related molecules between neurons. The second consists of homeoproteins like Otx2 that carry information from sense organs to primary sensory cortex. There is developing evidence that presynaptic neurons may be able to modulate the fine microanatomical structure in the postsynaptic neuron. This may be conducted by three mechanisms, of which the first is well established and the latter two are novel. (i) By the well-established activation of receptors that trigger a chain of signalling molecules (second messengers) that result in the upregulation and/or activation of a transcription factor. The two novel systems are the exosome system and homeoproteins. (ii) Exosomes are small vesicles that are released upon activation of the axon terminal, traverse the synaptic cleft, probably via astrocytes and are taken up by the postsynaptic neuron. They carry a load of signalling proteins and a variety of forms of RNA. These loads may then be transported widely throughout the postsynaptic neuron and engineer modulations in the fine structure of computational machinery by epigenetic-related processes. (iii) Otx2 is a transcription factor that, inter alia, controls the development and survival of PVþ GABAergic interneurons (PV cells) in the primary visual cortex. It is synthesized in the retina and is transported to the cortex by a presently unknown mechanism that probably includes direct cell-to-cell transfer, and may, or may not, include transfer by the dynein and exosome systems in addition. These three mechanisms explain a quantity of data from the field of de-and reafferentation plasticity. These data show that the modality of the presynaptic neuron controls to a large extent the modality of the postsynaptic neuron. However, the mechanism that effects this is currently unknown. The exosome and the homeoprotein hypotheses provide novel explanations to add to the well-established earlier mechanism described above.

Exosomes in stroke pathogenesis and therapy

“…Suppression of neuronal PTEN signals and reduction of an astrocyte scar promote axonal sprouting in adult CNS after spinal cord injury and stroke (57,59,92). Together, these data suggest that neuronal exosomes mediate synaptic and axonal plasticity by synaptic transfer of their cargo between neurons and by communication with astrocytes (86,93), which potentially mediate axonal and synaptic remodeling in the ischemic brain.…”

Glia–neuron interactions in the mammalian retina

“…AQP4 influences many process (the volume of the extracellular space, waste clearance, potassium buffering, cell migration and calcium signalling: Nagelhus and Ottersen, 2013) and significantly, its expression is altered in diabetic retinopathy (Qin et al, 2012). Astrocytes may play a role in the transport of exosomes with different cargos between neurons (Edelstein and Smythies, 2014;Kawikova and Askenase, 2014). In a laser-induced choroidal neovascularisation (CNV) model, retinal astrocytes release exosomes containing anti-angiogenic compounds that protect the eye from the deleterious effects of neovascularisation (Hajrasouliha et al, 2013).…”

Heat stress: A risk factor for skin carcinogenesis

“…and Cockayne Syndrome A (CSA) proteins, which have DNA-binding ability (Bianchi et al, 2014;Edelstein and Smythies, 2014). The Xeroderma Pigmentosum group B and D (XPB and XPD respectively) helicases of the 10-subunit transcription factor TFIIH then unwind the helix surrounding the lesion, creating short stretches of single stranded DNA (ssDNA) around the lesion (Qian et al, 2015).…”