A mitochondrial nexus in major depressive disorder: Integration with the psycho-immune-neuroendocrine network.

Nervous system processes, including cognition and affective state, fundamentally rely on mitochondria. Impaired mitochondrial function is evident in major depressive disorder (MDD), reflecting cumulative detrimental influences of both extrinsic and intrinsic stressors, genetic predisposition, and mutation. Glucocorticoid 'stress' pathways converge on mitochondria; oxidative and nitrosative stresses in MDD are largely mitochondrial in origin; both initiate cascades promoting mitochondrial DNA (mtDNA) damage with disruptions to mitochondrial biogenesis and tryptophan catabolism. Mitochondrial dysfunction facilitates proinflammatory dysbiosis while directly triggering immuno-inflammatory activation via released mtDNA, mitochondrial lipids and mitochondria associated membranes (MAMs), further disrupting mitochondrial function and mitochondrial quality control, promoting the accumulation of abnormal mitochondria (confirmed in autopsy studies). Established and putative mechanisms highlight a mitochondrial nexus within the psycho-immune neuroendocrine (PINE) network implicated in MDD. Whether lowering neuronal resilience and thresholds for disease, or linking mechanistic nodes within the MDD pathogenic network, impaired mitochondrial function emerges as an important risk, a functional biomarker, providing a therapeutic target in MDD. Several treatment modalities have been demonstrated to reset mitochondrial function, which could benefit those with MDD.

Using biochemical markers to assess the effects of imposed temperature stress on freshwater decapod crustaceans: Cherax quadricarinatus as a test case.

The effects of thermal stress can impact negatively on the abundance and distribution of temperature-sensitive species, particularly freshwater crustaceans. This study investigated the effects of thermal stress on physiological and biochemical parameters at five treatment temperatures resulting in minimal (25 °C), moderate (27, 29 °C) or severe (31, 33 °C) thermal stress in the common tropical freshwater crayfish Cherax quadricarinatus. The aim was to develop a suite of stress-sensitive assays to use on threatened populations of freshwater crustaceans, particularly those restricted to cooler temperatures and only found in high altitude refugia. Significant increases in indicators of oxidative and metabolic stress were observed at 29 °C and were elevated further at 33 °C. After a 50-day acclimation to an imposed temperature stress, significant changes in the level of total glutathione, total lipids, muscular protein, total haemocyte count, lipid peroxidation and protein carbonyls were observed between treatments while superoxide dismutase activity and haemolymph protein concentrations did not change. The data provided proof of concept that measuring key biochemical responses to high temperature can provide a means of contrasting the level of thermal stress experienced between individuals of the same species adapted to different temperatures. The methods developed are expected to be of use in research on wild populations of other freshwater poikilothermic organisms, particularly those susceptible to increased environmental temperatures associated with climate change.

Ecophysiology of neuronal metabolism in transiently oxygen-depleted environments: evidence that GABA is accumulated pre-synaptically in the cerebellum.

Interactions between coral reef topography, tide cycles, and photoperiod provided selection pressure for adaptive physiological changes in sheltered hypoxic niches to be exploited by specialized tropical reef fish. The epaulette shark Hemiscyllium ocellatum withstands cyclic hypoxia in its natural environment, many hours of experimental hypoxia, and anoxia for up to 5h. It shows neuronal hypometabolism in response to 5% oxygen saturation. Northern-hemisphere hypoxia- and anoxia-tolerant vertebrates that over-winter under ice alter their inhibitory to excitatory neurotransmitter balance to forestall brain ATP depletion in the absence of oxidative phosphorylation. GABA immunochemistry, HPLC analysis and receptor binding studies in H. ocellatum cerebellum revealed a heterogeneous regional accumulation of neuronal GABA despite no change in its overall concentration, and a significant increase in GABA(A) receptor density without altered binding affinity. Increased GABA(A) receptor density would protect the cerebellum during reoxygenation when transmitter release resumes. While all hypoxia- and anoxia-tolerant teleosts examined to date respond to low oxygen levels by elevating brain GABA, the phylogenetically older epaulette shark did not, suggesting that it uses an alternative neuroprotective mechanism for energy conservation. This may reflect an inherent phylogenetic difference, or represent a novel ecophysiological adaptation to cyclic variations in the availability of oxygen.