Aestivation and hypoxia-related events share common silent neuron trafficking processes (BMC Neuroscience)

Background: The availability of oxygen is a limiting factor for neuronal survival since low levels accountnot only for the impairment of physiological activities such as sleep-wake cycle, but above allfor ischemic-like neurodegenerative disorders. In an attempt to improve our knowledgeconcerning the type of molecular mechanisms operating during stressful states like that ofhypoxic conditions, attention was focused on eventual transcriptional alterations of some keyAMPAergic silent neuronal receptor subtypes (GluR1 and GluR2) along with HSPs and HIF-1alpha during either a normoxic or a hypoxic aestivation of a typical aquatic aestivator, i.e. thelungfish (Protopterus annectens). Results: The identification of partial nucleotide fragments codifying for both AMPA receptorsubtypes in Protopterus annectens displayed a putative high degree of similarity to that of notonly fish but also to those of amphibians, birds and mammals. qPCR and in situ hybridizationsupplied a very high (p < 0.001) reduction of GluR1 mRNA expression in diencephalic areasafter 6 months of aerial normoxic aestivation (6mAE). Concomitantly, high (p < 0.01) levelsof HSP70 mRNAs in hypothalamic, mesencephalic and cerebellar areas of both 6mAE andafter 6 months of mud hypoxic aestivation (6mMUD) were detected together with evidentapoptotic signals. Surprisingly, very high levels of GluR2 mRNAs were instead detected inthalamic along with mesencephalic areas after 6 days of normoxic (6dAE) and hypoxic(6dMUD) aestivation. Moreover, even short- and long-term hypoxic states featured highlevels of HIF-1alpha and HSP27 transcripts in the different brain regions of the lungfish. Conclusions: The distinct transcriptional variations of silent neurons expressing GluR1/2 and HSPs tend tocorroborate these factors as determining elements for the physiological success of normoxicand hypoxic aestivation. A distinct switching among these AMPA receptor subtypes duringaestivation highlights new potential adaptive strategies operating in key brain regions of thelungfish in relation to oxygen availability. This functional relationship might have therapeuticbearings for hypoxia-related dysfunctions, above all in view of recently identified silentneuron-dependent motor activity ameliorations in mammals.