The primary physiological function of mitochondria is to generate adenosine triphosphate through oxidative phosphorylation via the electron transport chain. Overproduction of reactive oxygen species (ROS) as byproducts generated from mitochondria have been implicated in acute brain injuries such as stroke from cerebral ischemia. It was well-documented that mitochondria-dependent apoptotic pathway involves pro- and anti-apoptotic protein binding, release of cytochrome c, leading ultimately to neuronal death. On the other hand, mitochondria also play a role to counteract the detrimental effects elicited by excessive oxidative stress. Recent studies have revealed that oxidative stress and the redox state of ischemic neurons are also implicated in the signaling pathway that involves peroxisome proliferative activated receptor-γ (PPARγ) co-activator 1α (PGC1-α). PGC1-α is a master regulator of ROS scavenging enzymes including manganese superoxide dismutase 2 and the uncoupling protein 2, both are mitochondrial proteins, and may contribute to neuronal survival. PGC1-α is also involved in mitochondrial biogenesis that is vital for cell survival. Experimental evidence supports the roles of mitochondrial dysfunction and oxidative stress as determinants of neuronal death as well as endogenous protective mechanisms after stroke. This review aims to summarize the current knowledge focusing on the molecular mechanisms underlying cerebral ischemia involving ROS, mitochondrial dysfunction, apoptosis, mitochondrial proteins capable of ROS scavenging, and mitochondrial biogenesis.

Social interactions among animals mediate essential behaviours, including mating, nurturing, and defence 1,2 . The gut microbiota contribute to social activity in mice 3,4 , but the gut-brain connections that regulate this complex behaviour and its underlying neural basis are unclear 5,6 . Here we show that the microbiome modulates neuronal activity in specific brain regions of male mice to regulate canonical stress responses and social behaviours. Social deviation in germ-free and antibiotic-treated mice is associated with elevated levels of the stress hormone corticosterone, The Author(s), under exclusive licence to Springer Nature Limited 2021

Summary Purpose:  One cellular consequence of status epilepticus is apoptosis in the hippocampal CA3 subfield. We evaluated the hypothesis that the repertoire of cellular events that underlie such elicited cell death entails mitochondrial dysfunction induced by an excessive production of nitric oxide synthase II (NOS II)‐derived NO, increased superoxide anion (O2−) production, and peroxynitrite formation. Methods:  In Sprague‐Dawley rats, kainic acid was microinjected unilaterally into the hippocampal CA3 subfield to induce bilateral seizure‐like electroencephalography (EEG) activity. The effects of pretreatments with various test agents on the induced O2− production, peroxynitrite formation, mitochondrial respiratory chain enzyme activities, cytochrome c/caspase‐3 signaling, and DNA fragmentation in bilateral CA3 subfields were examined. Results:  Significantly and temporally correlated increase in O2− and peroxynitrite levels (3 to 24 h), depressed mitochondrial Complex I activity (3 h), enhanced translocation of cytochrome c to cytosol (day 1), and augmented activated caspase‐3 (day 7) and DNA fragmentation (day 7) were detected bilaterally in hippocampal CA3 subfields after the elicitation of sustained seizure. Pretreatment with microinjection into the bilateral hippocampal CA3 subfield of a water‐soluble formulation of coenzyme Q10; a selective NOS II inhibitor, S‐methylisothiourea; a superoxide dismutase mimetic, 4‐hydroxy‐2,2,6,6‐tetramethylpiperidine‐1‐oxyl; an active peroxynitrite decomposition catalyst, 5,10, 15,20‐tetrakis‐(N‐methyl‐4‐pyridyl)‐ porphyrinato iron (III); or a peroxynitrite scavenger, L‐cysteine significantly blunted these cellular events. Discussion:  Prolonged seizures prompted NO‐, O2−‐, and peroxynitrite‐dependent reduction in mitochondrial respiratory enzyme Complex I activity, leading to cytochrome c/caspase‐3‐dependent apoptotic cell death in the hippocampal CA3 subfield after induction of experimental temporal lobe status epilepticus.