Aestivation and hypoxia-related events share common silent neuron trafficking processes

Abstract

BackgroundThe availability of oxygen is a limiting factor for neuronal survival since low levels account not only for the impairment of physiological activities such as sleep-wake cycle, but above all for ischemic-like neurodegenerative disorders. In an attempt to improve our knowledge concerning the type of molecular mechanisms operating during stressful states like those of hypoxic conditions, attention was focused on eventual transcriptional alterations of some key AMPAergic silent neuronal receptor subtypes (GluR1 and GluR2) along with HSPs and HIF-1α during either a normoxic or a hypoxic aestivation of a typical aquatic aestivator, i.e. the lungfish (Protopterus annectens).ResultsThe identification of partial nucleotide fragments codifying for both AMPA receptor subtypes in Protopterus annectens displayed a putative high degree of similarity to that of not only fish but also to those of amphibians, birds and mammals. qPCR and in situ hybridization supplied a very high (p < 0.001) reduction of GluR1 mRNA expression in diencephalic areas after 6 months of aerial normoxic aestivation (6mAE). Concomitantly, high (p < 0.01) levels of HSP70 mRNAs in hypothalamic, mesencephalic and cerebellar areas of both 6mAE and after 6 months of mud hypoxic aestivation (6mMUD) were detected together with evident apoptotic signals. Surprisingly, very high levels of GluR2 mRNAs were instead detected in thalamic along with mesencephalic areas after 6 days of normoxic (6dAE) and hypoxic (6dMUD) aestivation. Moreover, even short- and long-term hypoxic states featured high levels of HIF-1α and HSP27 transcripts in the different brain regions of the lungfish.ConclusionsThe distinct transcriptional variations of silent neurons expressing GluR1/2 and HSPs tend to corroborate these factors as determining elements for the physiological success of normoxic and hypoxic aestivation. A distinct switching among these AMPA receptor subtypes during aestivation highlights new potential adaptive strategies operating in key brain regions of the lungfish in relation to oxygen availability. This functional relationship might have therapeutic bearings for hypoxia-related dysfunctions, above all in view of recently identified silent neuron-dependent motor activity ameliorations in mammals.

Perturbations of Respiratory Rhythm and Pattern by Disrupting Synaptic Inhibition within Pre-Bötzinger and Bötzinger Complexes

“…It has been postulated that phasic synaptic inhibition originating in these circuits, known to contain populations of rhythmically active glycinergic and GABAergic neurons, are critically involved in generating the three-phase pattern of respiratory neuron activity during normal breathing by shaping firing patterns of active populations of neurons, orchestrating phase transitions, and controlling which populations are inactive during each phase ( Rybak et al, 2004, 2007 ; Smith et al, 2007 , 2009,2013 ). Inspiratory and expiratory neurons in these regions receive phasic volleys of inhibitory post-synaptic potentials/currents as clearly established by intracellular recordings ( Schmid et al, 1996 ; Molkov et al, 2012 ; Shevtsova et al, 2014 ; Richter and Smith, 2014 ), and the inhibitory neurons in the pre-BötC and BötC are proposed to interact during the respiratory cycle via mutual inhibitory connections for dynamic control of rhythm generation, although these interactions have not been definitely established experimentally.…”

Differential Gene Expression in the Brain of the African Lungfish, Protopterus annectens, after Six Days or Six Months of Aestivation in Air

“…Only until very recently, did Loong et al [11], [12] report on the differential gene expression, and the up-regulation of mRNA expression of carbamoyl phosphate synthetase III and ornithine-urea cycle capacity, in the liver of P. annectens during the induction phase (the first 6 days) of aestivation in air. More importantly, there are very few recent studies [13], [14] on the brain of aestivating African lungfish in spite of its possible role in coordinating a whole-body aestivation-specific response during the induction phase of aestivation. Therefore, this study was undertaken to examine, using suppression subtractive hybridization (SSH) polymerase chain reaction (PCR), the up- and down-regulation of gene expression in the brain of P. annectens during the induction phase (6 days) or the prolonged maintenance phase (6 months) of aestivation in air with reference to the freshwater control.…”

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“…It could be argued that behavioral changes, particularly hibernation of C. striatus during O 2 deficiency, could well be associated with a phenomenon of estivation rather than hypoxia. Ho wever, estivation is linked to hypoxia (Brooks & Storey, 1990;Whitwam & Storey, 1990), where physiological adaptive mechanis ms of hypoxia and estivation share several common features (Giusi et al, 2012).…”