Mitochondrial brain proteome acetylation levels and behavioural responsiveness to amphetamine are altered in mice lacking Sirt3.

Post-translational modification of mitochondrial proteins represents one mechanism by which the functional activity of mitochondria can be regulated. In the brain, these modifications can influence the functional properties of different neural circuitries. Given that the sirtuin family member Sirt3 represents the primary protein deacetylase enzyme in mitochondria, we tested whether brain mitochondrial proteome acetylation would increase in male or female mice lacking Sirt3.

The Role of SIRT3 in the Brain Under Physiological and Pathological Conditions.

Sirtuin enzymes are a family of highly seven conserved protein deacetylases, namely SIRT1 through SIRT7, whose enzymatic activities require the cofactor nicotinamide adenine dinucleotide (NAD). Sirtuins reside in different compartments within cells, and their activities have been shown to regulate a number of cellular pathways involved in but not limited to stress management, apoptosis and inflammatory responses. Given the importance of mitochondrial functional state in neurodegenerative conditions, the mitochondrial SIRT3 sirtuin, which is the primary deacetylase within mitochondria, has garnered considerable recent attention.

mRNA expression of transient receptor potential melastatin (TRPM) channels 2 and 7 in perinatal brain development.

TRPM7 and TRPM2 are non-specific cation channels of the Transient Receptor Potential channel superfamily. Each channel has gained attention for their potential to mediate oxidative and anoxic cell death (Rama and García, 2016; Nazıroğlu, 2011a; Abiria et al., 2017; Sun, 2017), however their physiological expression and roles in the developing brain remain poorly defined.

ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia.

Background: Malignant gliomas are highly invasive, difficult to treat, and account for 2% of cancer deaths worldwide. Glioblastoma Multiforme (GBM) comprises the most common and aggressive intracranial tumor. The study hypothesis is to investigate the modification of Photodynamic Therapy (PDT) efficacy by mild hypothermia leads to increased glioma cell kill while protecting normal neuronal structures.

A Role for Diminished GABA Transporter Activity in the Cortical Discharge Phenotype of MeCP2-Deficient Mice.

Cortical network hyper-excitability is a common phenotype in mouse models lacking the transcriptional regulator methyl-CPG-binding protein 2 (MeCP2). Here, we implicate enhanced GABAB receptor activity stemming from diminished cortical expression of the GABA transporter GAT-1 in the genesis of this network hyper-excitability. We found that administering the activity-dependent GABAB receptor allosteric modulator GS-39783 to female Mecp2(+/-) mice at doses producing no effect in wild-type mice strongly potentiated their basal rates of spontaneous cortical discharge activity.

Differential expression of sirtuin family members in the developing, adult, and aged rat brain.

The sirtuins are NAD(+)-dependent protein deacetylases and/or ADP-ribosyltransferases that play roles in metabolic homeostasis, stress response and potentially aging. This enzyme family resides in different subcellular compartments, and acts on a number of different targets in the nucleus, cytoplasm and in the mitochondria. Despite their recognized ability to regulate metabolic processes, the roles played by specific sirtuins in the brain-the most energy demanding tissue in the body-remains less well investigated and understood.

Over-expression of the Sirt3 sirtuin Protects neuronally differentiated PC12 Cells from degeneration induced by oxidative stress and trophic withdrawal.

Sirt3 is a mitochondrial sirtuin whose deacetylase activity regulates facets of oxidative metabolic efficiency, anti-oxidative capacity, and intra-mitochondrial signaling. In this study, we tested whether the over-expression of a human Sirt3-myc transgene in differentiated PC12 cells, a model of sympathetic catecholaminergic neurons, would affect the sensitivity of these cells to oxidative stress or trophic withdrawal insults. Expression analysis revealed the Sirt3-myc product was expressed as a 45kDa pro-form, which localized primarily within the cytosol, and a 30kDa processed form that localized predominantly within mitochondria.