Neuroscience
-
Although many physiological adaptations of diving mammals have been reported, little is known about how their brains sustain the high demands for metabolic energy and thus O(2) when submerged. A recent study revealed in the deep-diving hooded seal (Cystophora cristata) a unique shift of the oxidative energy metabolism and neuroglobin, a respiratory protein that is involved in neuronal hypoxia tolerance, from neurons to astrocytes. Here we have investigated neuroglobin in another pinniped species, the harp seal (Pagophilus groenlandicus), and in two cetaceans, the harbor porpoise (Phocoena phocoena) and the minke whale (Balaenoptera acutorostrata). ⋯ Thus neuroglobin appears to play a specific role in diving mammals, but seals and whales have evolved divergent strategies to cope with cerebral hypoxia. The specific function of neuroglobin that conveys hypoxia tolerance may either relate to oxygen supply or protection from reactive oxygen species. The different strategies in seals and whales resulted from a divergent evolution and an independent adaptation to diving.
-
In two experiments, we combined a semantic blocked naming paradigm with anodal transcranial direct current stimulation (tDCS) to shed light on the neural correlates of the semantic interference (SI) effect. In particular, prior to the naming task, anodal tDCS was applied over the left superior temporal gyrus (STG, Experiment 1) or the left inferior frontal gyrus (IFG, Experiment 2) to enhance cortical excitability in these regions. ⋯ Overall, our data confirm the existence of a distributed cortical network involved in lexical retrieval and show that both the left IFG and the left STG play a causal role in this process. In particular, the left IFG is likely to be critical in resolving the conflict between competitor lexical representations, while the left STG seems to be the neural locus of the lexical representational system, where competition among different lexical representations occurs.
-
Astrocytes perform several functions that are essential for normal neuronal activity. They play a critical role in neuronal survival during ischemia and other degenerative injuries and also modulate neuronal recovery by influencing neurite outgrowth. In this study, we investigated the neuroprotective effects of astrocyte-derived 14,15-epoxyeicosatrienoic acid (14,15-EET), metabolite of arachidonic acid by cytochrome P450 epoxygenases (CYP), against oxidative stress induced by hydrogen peroxide (H(2)O(2)). ⋯ However, pretreatment with the CYP epoxygenase inhibitor miconazole (1-20 μM, 1h) before H(2)O(2) (1mM, 1h) stimulation showed decreased cell viability. Our data suggest that 14,15-EET which is released from astrocytes, enhances cell viability against oxidant-induced injury. Further understanding of the mechanism of 14,15-EET-mediated protection in dopaminergic neurons is imperative, as it could lead to novel therapeutic approaches for treating CNS neuropathologies, such as Parkinson's disease.
-
Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. ⋯ Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in the inhibitory effects of minocycline upon AMPH-elicited action potential bursts.
-
Comparative Study
Geldanamycin accelerated peripheral nerve regeneration in comparison to FK-506 in vivo.
FK-506 accelerates nerve regeneration and improves functional recovery in vivo; its immunosuppressive properties, however, limit its clinical utility. Geldanamycin (GA), a non-immunosuppressive agent, shares a common binding target (heat shock protein 90) with FK-506 and may accelerate nerve regeneration through a similar mechanism. GA has been shown to augment neurite outgrowth in vitro but has not been tested in vivo. ⋯ GA, however, did not match the performance of FK-506 in injury models where Wallerian degeneration (WD) is ongoing in the distal stump. This provides evidence that FK-506 accelerates axonal regeneration through two parallel mechanisms: the first being its well-established effect on neurons; the second is likely a newly described, as-yet poorly defined mechanism that affects WD. Finally, given the decrease in observed toxicity with GA administration, it might be a suitable non-immunosuppressive alternative to FK-506 for accelerating peripheral nerve regeneration in cases of clinical nerve injury.