Neuroscience
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In the present study, we investigated whether endoplasmic reticulum (ER) stress is associated with neuronal- and astroglial-death in the hippocampus using LiCl-pilocarpine-induced status epilepticus (SE) rat model. Glucose-related protein (GRP) 78 and protein disulfide isomerase (PDI) expressions were transiently increased in CA1 neurons and dentate granule cells, and subsequently decreased in these cells following SE. GRP94 and calnexin (CNX) expression was gradually reduced in CA1 neurons, not in dentate granule cells. ⋯ In the molecular layer of the dentate gyrus, PDI-positive astrocytes showed TUNEL signal, nuclear apoptosis inducing factor translocation and pPERK/peIF2A/CHOP immunoreactivities. Four weeks after SE, clasmatodendritic astrocytes showed pPERK peIF2A and CNX immunoreactivities without CHOP expression. These findings indicate that SE-induced ER stress may be associated with astroglial apoptosis and autophagic astroglial death in the regional-specific pattern.
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It has been proposed that spontaneous panic attacks are the outcome of the misfiring of an evolved suffocation alarm system. Evidence gathered in the last years is suggestive that the dorsal periaqueductal gray (dPAG) in the midbrain harbors a hypoxia-sensitive suffocation alarm system. We here investigated whether facilitation of 5-HT-mediated neurotransmission within the dPAG changes panic-like defensive reactions expressed by male Wistar rats submitted to a hypoxia challenge (7% O2), as observed in other animal models of panic. ⋯ These effects were similar to those caused by chronic, but not acute, intraperitoneal administration of the antidepressant fluoxetine (5-15 mg/kg), or acute systemic administration of the benzodiazepine receptor agonist alprazolam (1-4 mg/kg), both drugs clinically used in the treatment of panic disorder. Our findings strengthen the view that the dPAG is a key encephalic area involved in the defensive behaviors triggered by activation of the suffocation alarm system. They also support the use of hypoxia-evoked escape as a model of respiratory-type panic attacks.
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Glutamatergic synaptic activity entails a high energetic cost. During aging, a variety of neural metabolic changes have been reported that could compromise the capacity of neural circuits to maintain synaptic transmission during periods of reduced extracellular glucose. Indeed, a preferential compromise in evoked synaptic activity has been observed in hippocampal CA1 with age during exposure to low-glucose solutions. ⋯ However, orthodromic-evoked population spike amplitude and field excitatory post-synaptic potential (EPSP) slope were preferentially decreased in slices from aged rats during exposure to 1mM glucose-aCSF. Antidromic population spike amplitude was not differentially affected in slices from aged versus adult rats, however. These data suggest that synaptic efficacy is preferentially compromised with age under reduced glucose availability and, combined with a decreased capacity of the periphery to provide glucose to the central nervous system (CNS) during metabolically challenging conditions, could contribute to aging-related hippocampal dysfunction and cognitive decline.
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Spinal ephrinB-EphB signaling is involved in the modulation of pain processing. The aim of the present study was to investigate whether protein kinase C-γ (PKCγ) acts as a downstream effector in regulating spinal pain processing associated with ephrinB-EphB signaling in mice. The intrathecal injection of ephrinB2-Fc, an EphB receptor activator, caused thermal hyperalgesia and mechanical allodynia, as well as increased activation of spinal PKCγ. ⋯ Furthermore, the intrathecal injection of EphB2-Fc, an EphB receptor blocker, suppressed formalin-induced inflammatory, chronic constriction injury (CCI)-induced neuropathic, and tibia bone cavity tumor cell implantation (TCI)-induced bone cancer pain behaviors, in addition to reducing the activation of spinal PKCγ. Finally, the intrathecal injection of MK801, an N-methyl-D-aspartate (NMDA) receptor blocker, prevented the pain behaviors and spinal PKCγ activation induced by ephrinB2-Fc. Overall, the results confirm the important role of PKCγ in the regulation of spinal pain processing associated with ephrinB-EphB signaling.
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Identifying novel neuroprotectants that can halt or even reverse the effects of stroke is of interest to both clinicians and scientists. Neuregulin 1 (NRG1) is an effective neuroprotectant, but its molecular mechanisms are largely unclear. ⋯ Importantly, NRG1 neuroprotection against brain ischemia was abolished in the mice with specific deletion of ErbB4 in parvalbumin (PV)-positive interneurons. In summary, NRG1 protects against ischemic brain injury via ErbB4 receptors by enhancing GABAergic transmission.