Brain Metabolic DNA: A Long Story and Some Conclusions.

We have previously outlined the main properties of brain metabolic DNA (BMD) and its involvement in circadian oscillations, learning, and post-trial sleep. The presence of BMD in certain subcellular fractions and their behavior in cesium gradients have suggested that BMD originates from cytoplasmic reverse transcription and subsequently acquires a double-stranded configuration. More recently, it has been reported that some DNA sequences of cytoplasmic BMD in learning mice are different from that of the control animals.

Brain metabolic DNA: recent evidence for a mitochondrial connection.

This review highlights recent data concerning the synthesis of brain metabolic DNA (BMD) by cytoplasmic reverse transcription and the prompt acquisition of the double-stranded configuration that allows its partial transfer to nuclei. BMD prevails in the mitochondrial fraction and is present in presynaptic regions and astroglial processes where it undergoes a turnover lasting a few weeks. Additional data demonstrate that BMD sequences are modified by learning, thus indicating that the modified synaptic activity allowing proper brain responses is encoded in learning BMD.

Sequences of Reverse Transcribed Brain DNA Are Modified by Learning.

Brain metabolic DNA (BMD) is continuously synthesized by reverse transcription in presynaptic synaptosomes and astroglia, and is partly transferred to nuclei after acquiring the double stranded configuration. Synthesis and turnover of BMD are markedly dependent on brain activity, as shown by circadian oscillations, environmental enrichment and impoverishment, and a variety of learning protocols. In rodents learning a two-way active avoidance task, BMD synthesis doubles, thus raising the possibility that sequences of learning BMD may differ from control BMD.

Brain Metabolic DNA Is Reverse Transcribed in Cytoplasm: Evidence by Immunofluorescence Analysis.

In a previous study (Mol Neurobiol 55:7476-7486, 2017), newly synthesized brain metabolic DNA (BMD) from rat subcellular fractions has been shown to behave as a DNA-RNA hybrid when analyzed in cesium gradients at early [H] thymidine incorporation times but to assume the double-stranded configuration at later times. Conversely, BMD from purified nuclei displayed the dsDNA configuration even at early incorporation times. The results were interpreted to support the BMD origin by reverse transcription in the cytoplasm and its later acquisition of the double-stranded configuration before the partial transfer to the nuclei.