Mild mitochondrial inhibition in vivo enhances glutamate-induced neuronal damage through calpain but not caspase activation: Role of ionotropic glutamate receptors

Vitamin E deficiency during embryogenesis in zebrafish causes lasting metabolic and cognitive impairments despite refeeding adequate diets

“…We also found E− larvae had increased levels of glutamate (p< 0.001; Supplementary Table 1) relative to E+ larvae, which could signify glutamate toxicity, another metabolic perturbation associated with ferroptosis [53] via inhibition of the cellular cysteine/glutamate antiporter system X c - [51]. Excessive glutamate is neurotoxic [58] and may be a consequence of compromised mitochondria [59]; additional experiments regarding the regulation of neuronal intracellular glutamate levels are required to determine whether these mechanisms also apply to our VitE deficiency model. Importantly, VitE supplementation successfully prevents ferroptosis [60] and associated neurological impairments [61], while VitE deficiency exacerbates the latter [62], indicating that ferroptosis may constitute a biological rationale for the consequences of embryonic VitE deficiency we observed in E− larvae.…”

3-Nitropropionic Acid as a Tool to Study the Mechanisms Involved in Huntington’s Disease: Past, Present and Future

“…More recently, an emerging line of research has provided interesting models to study integrative toxic events occurring in neurodegenerative disorders, including HD. These models comprehend the facilitation of excitotoxic events through the impairment of energy metabolism, and are produced by the combination of toxic molecules in different biological systems and under different experimental conditions, thus turning the neuronal cells more vulnerable to “regular” or moderately high concentrations of excitatory agents, further leading to excitotoxic damage by means of indirect overactivation of NMDA-R (“secondary excitotoxicity”), and cell death [ 235 , 236 , 237 , 238 ]. Specifically, this kind of toxic events result from the facilitation of NMDA-R since the impairment in energy metabolism decreases the ATP needed to maintain membrane potential, leading cells to sustained depolarization mediated by a lack of ATPases activity, and this process in turn, will produce activation of voltage-gated NMDA-R. A further study supported this concept by testing malonate (a reversible inhibitor of Complex II at the ETC) at sub-umbral concentrations, in the presence of glutamate, NMDA or AMPA) [ 239 ].…”

Modulation of the autophagy‐lysosomal pathway and endoplasmic reticulum stress by ketone bodies in experimental models of stroke

“…The effect of D-BHB i.p administration followed by its continuous epidural infusion during 48 h on the lesion volume and the number of The proteolytic processing of the cytoskeletal protein α-spectrin has been commonly used as a marker of ischemic and excitotoxic brain injury (Del Rio & Massieu, 2008;Liu et al, 2021;Roberts-Lewis et al, 1994;Roberts-Lewis & Siman, 1993;Siman et al, 1984). This protein is a typical substrate of calpain generating two fragments of 145 and 150 kDa (α-spectrin breakdown products, SBDP), respectively (Liu et al, 2021;Roberts-Lewis et al, 1994;Siman et al, 1984).…”

“…In contrast, the nonphysiological isomer L-BHB had no significant effect on the lesion volume or the number of FJ-B-positive cells (Figure2a,b). No FJ-B-positive cells were observed in intact controls, the contralateral side to the ischemic lesion (data not shown) or sham-operated animals (Figure2b).The proteolytic processing of the cytoskeletal protein α-spectrin has been commonly used as a marker of ischemic and excitotoxic brain injury(Del Rio & Massieu, 2008;Liu et al, 2021;…”