Brain AMPAR-dependent synaptic trafficking mechansims during lungfish aestivating conditions are comparable to ischemic states

Oxygen availability is a limiting factor for neuronal survival as displayed by its scarce levels inducing the impairment of physiological activities such as sleep-wake cycle and motor functions. This study attempts to highlight a direct relationship between different aestivation states under normoxic and hypoxic conditions of the lungfish (Protopterus annectens) with the excitatory-dependent regulation of AMPAR subtypes (GluR1 and GluR2). In a first stage, greatly (p<0.01) evident expression levels of the hypoxia-inducible factor 1 (HIF-1) along with neuroprotective chaperones, i.e. heat shock proteins 27 and 70 (HSP27 and 70), were tightly correlated to densely apoptotic cells throughout the different brain regions especially under hypoxic conditions (6dMUD and 6mMUD). In addition, only GluR2 mRNA levels of telencephalic and hypothalamic areas seemed to overlap consistent up-regulations of HIF-1 plus HSP (27,70) and consequently apoptotic cellular phenomenon during such hypoxic states. Conversely, under normoxic conditions HSP70 resulted to be very greatly expressed throughout most of the hypothalamic, mesencephalic and cerebellar areas. In these same regions, a very great (p<0.001) down- and up-regulation of GluR1 and of GluR2 mRNAs levels, respectively, was detected especially under a brief normoxic condition (6dAE). These first results tend to corroborate distinct AMPAR-dependent synaptic trafficking strategies that together with HSPs are responsible for the physiological success of lungfish aestivation during both normoxic and hypoxic conditions. Overall, the possibility of correlating apoptotic responses plus the activation of specific AMPAR subunits in this hypoxia tolerant species to those of mammals ischemic events might have therapeutic bearings for hypoxic-dependent neurodegenerative disease.