The transcriptome signature of the mouse brain after bulbectomy suggests a new model of Alzheimer's disease with elements of major depression.

In general, analysis of the functional significance of genes in the brain of OBX mice indicates that the balance of the GABA/glutamatergic systems is disturbed with hyperactivation of the latter, which leads to the development of excitotoxicity and induction of apoptosis on the background of severe mitochondrial dysfunction and astrogliosis. The synthesis of neurotrophic factors decreases, which leads to disruption of the cytoskeleton of neurons, an increase in the level of intracellular calcium, and activation of tau protein phosphorylation. The acetylcholinergic system is deficient on the background of hyperactivation of acetylcholinesterase. Importantly, the activity of the dopaminergic, endorphin, and opiate systems decreases, and hormonal dysfunction develops. Genes associated with the regulation of circadian rhythms, cell migration, and impaired innate immunity are activated. All this occurs on the background of down-regulation of genes of ribosomal proteins. It is clear that OBX mice are a model of complex neuropathology with elements of Alzheimer's disease and major depression. This model with a certain degree of probability can be attributed to subtype B2 in humans. Overall design: Single-end RNA-seq of dissected brain tissues from Sham-operated and bulbectomic mice