Stress,Aging, and Brain Oxidative Damage

Stress may contribute to aging acceleration and age-related degenerative diseases. Stress and adaptation to stress require numerous homeostatic adjustments including hormones, neurotransmitters, oxidants, and other mediators. The stress-induced hormones, neurotransmitters, and oxidants all have beneficial, but also harmful effects if out of balance. Therefore, the homeostasis of stress and adaptation should be governed by the hormone balance, neurotransmitter balance, and oxidant balance, as well as the interactions among these substances. The imbalance and the over-interaction of these balances may ultimately cause increased oxidant generation and oxidative damage to biomolecules. This increased oxidative damage may add to the oxidant burden associated with normal aerobic metabolism, which in itself, generates oxidants, causes accumulation of oxidative damage in mitochondria, and contributes to normal aging. Therefore, the stress-associated increase of oxidative damage may, in part, contribute to stress-associated aging acceleration and age-related neurodegenerative diseases.     

Distribution Pattern of γ-amino Butyric Acid Immunoreactive Neural Structures in the Central and Peripheral Nervous System of the Tubificid Worm, Limnodrilus hoffmeisteri

By means of whole-mount immunohistochemistry, putative inhibitory (GABAergic) neural structures were identified in the central and peripheral nervous system of the tubificid worm, Limnodrilus hoffmeisteri. In the supraoesophageal ganglion (brain) only few strongly labelled cells were observed. However, in its commissural part a high number of stained nerve fibres, arising mainly from the ventral nerve cord and prostomium, occurred. Except for the suboesophageal ganglion the arrangement of γ-amino butyric acid-immunoreactive (GABA-IR) structures proved to be identical in each VNC ganglion. Behind the first segmental nerves three pairs of heavily stained neurones were located. Their processes (both ipsi- and contralateral) form four bundles of fine-fibred polysegmental interneuronal tracts that run close to the dorsal giant axons from the terminal ganglion to the suboesophageal one without interruption. A few small motoneurons and a pair of large ones with contralateral processes were also identified. A bipolar (presumably sensory) neuron was located at the root of each second segmental nerve. GABA-IR neurons were also found in the stomatogastric ganglia and pharyngeal wall; however, the latter structure had a well-developed fibre network, as well. Present results suggest that GABA acts as a common neurotransmitter in sensory, interneuronal and motor system of L. hoffmeisteri. The possible functional role of the identified GABA-IR neural structures in locomotion, escape and withdrawal reflexes in tubificid worms is discussed.     

Effect of music stimulus on gilthead seabream Sparus aurata physiology under different light intensity in a re‐circulating water system

The aim of the present study was to evaluate music effects (Mozart, K525) on gilthead seabream Sparus aurata and investigate whether its response to music was differentiated when combined with different lighting conditions. Therefore, S. aurata (mean ±s .e . 1·51 ± 0·01 g) were reared in re‐circulating water system under 80 and 200 lx and subjected to 2 and 4 h of music transmissions or to no music at all (control, ambient noise only). Underwater ambient noise of the equipment (e.g. pumps and aerators) in all experimental tanks was 121 dB re 1 μPa and music transmitted was set at 140 dB re 1 μPa. During the first 89 days of rearing, music resulted in enhanced growth. Nevertheless, at the end of the experiment (on day 117) no significant differences were found for body mass but music treatment resulted in more homogeneous fish populations than controls. Brain neurotransmitter levels were reduced especially when music transmission was combined with 200 lx. Feed utilization was significantly improved when fish were subjected to 4 h of music and 200 lx, while stomach proteolytic enzymes and intestine total carbohydrases were lower and higher, respectively, compared to controls. Some differences were also observed in liver and plasma fatty acids composition. The present results provide the initial evidence that music transmission under specific rearing conditions could have enhancing effects on S. aurata growth performance, at least at specific fish sizes. Moreover, the observed music effects on several aspects of fish physiology (e.g. digestive enzymes, fatty acid composition and brain neurotransmitters) imply that music could possibly provide even further enhancement in growth, quality, welfare and production.     

Nootropic effect of neferine on aluminium chloride–induced Alzheimer's disease in experimental models

Alzheimer's disease (AD) is an age‐associated neurodegenerative disease, which is developed by oxidative stress and acetylcholine contraction in the synaptic cleft of the neurons. This leads to dementia, memory loss, and decrease in learning ability and orientation. In this research work, we aimed to explore the neuroprotective effect of neferine on AlCl₃‐induced AD in rats. The results of our study revealed that the increased reactive oxygen species (ROS) and nitric oxide in the hippocampus leads to the development of AD in the rats. The oral treatment of neferine done the following occurrences such as; it potentially inhibited the ROS formation and acts as a scavenging molecule by preventing the neurodegeneration. It also improved the memory and learning ability to complete the maze activity in the AD rats and significantly increased the antioxidants superoxide dismutase, catalase, and reduced glutathione in neferine treated AD rats. It aggressively declined the activity of acetylcholine esterase and Na⁺K⁺ATPase in the neurodegenerative rat models. The gene expression pattern of neuroinflammatory cytokines such as tumor necrosis factor α (TNF‐α), interleukin‐6 (IL‐6), and interleukin‐1β (IL‐1β) were decreased in the neferine‐treated rats. The neuroinflammatory proteins such as inducible nitric oxide (iNOS), cyclooxygenase‐2 (COX‐2), and nuclear factor kappa β (Nf‐κβ) were decreased and Nf‐κβ inhibitor IKBα was increased in the neferine‐treated AD rats. Finally, the histology study proved that the neferine treatment possibly prevents neurodegeneration in the hippocampus tissue of the AD models. Hence, these all findings concluded that the neferine could be a potential neuropreventive as well as neurodegenerative therapeutic compound in neurological and cognitive dysfunction.     

The role of the microbiome in the neurobiology of social behaviour

Microbes colonise all multicellular life, and the gut microbiome has been shown to influence a range of host physiological and behavioural phenotypes. One of the most intriguing and least understood of these influences lies in the domain of the microbiome's interactions with host social behaviour, with new evidence revealing that the gut microbiome makes important contributions to animal sociality. However, little is known about the biological processes through which the microbiome might influence host social behaviour. Here, we synthesise evidence of the gut microbiome's interactions with various aspects of host sociality, including sociability, social cognition, social stress, and autism. We discuss evidence of microbial associations with the most likely physiological mediators of animal social interaction. These include the structure and function of regions of the ‘social' brain (the amygdala, the prefrontal cortex, and the hippocampus) and the regulation of ‘social’ signalling molecules (glucocorticoids including corticosterone and cortisol, sex hormones including testosterone, oestrogens, and progestogens, neuropeptide hormones such as oxytocin and arginine vasopressin, and monoamine neurotransmitters such as serotonin and dopamine). We also discuss microbiome‐associated host genetic and epigenetic processes relevant to social behaviour. We then review research on microbial interactions with olfaction in insects and mammals, which contribute to social signalling and communication. Following these discussions, we examine evidence of microbial associations with emotion and social behaviour in humans, focussing on psychobiotic studies, microbe–depression correlations, early human development, autism, and issues of statistical power, replication, and causality. We analyse how the putative physiological mediators of the microbiome–sociality connection may be investigated, and discuss issues relating to the interpretation of results. We also suggest that other candidate molecules should be studied, insofar as they exert effects on social behaviour and are known to interact with the microbiome. Finally, we consider different models of the sequence of microbial effects on host physiological development, and how these may contribute to host social behaviour.     

The opercular gland of the cleaner-wrasse Labroides dimidiatus (Labridae), a light-, electron and scanning electron microscopic investigation

A histological and ultrastructural examination of the opercular gland of the cleaner-wrasse Labroides dimidiutus has demonstrated that the slimy envelope which covers the animal at night is mainly produced by large mucous goblet cells in a folded epithelium; there is a high number of acidophilic secretory cells. At the ultrastructural level, both cell-types open at the surface of the epidermis. Preliminary experiments with pilocarpine, atropine and the α-blocker propranolol reveal a neural regulation of mucus discharge. Also, the rich vascularization of the gland could indicate a hormonal control e.g. by prolactin. The secretory products of both types of goblet cells are discussed in relation to their possible antibiotic properties.     

Genetic biomarkers of depression

Depression is a term that has been used to describe a variety of ailments, ranging from minor to incapacitating. Clinically significant depression, termed as major depression, is a serious condition characterized not only by depressed mood but also by a cluster of somatic, cognitive, and motivational symptoms. Significant research efforts are aimed to understand the neurobiological as well as psychiatric disorders, and the evaluation of treatment of these disorders is still based solely on the assessment of symptoms. In order to identify the biological markers for depression, we have focused on gathering information on different factors responsible for depression including stress, genetic variations, neurotransmitters, and cytokines and chemokines previously suggested to be involved in the pathophysiology of depression. The present review illustrates the potential of biomarker profiling for psychiatric disorders, when conducted in large collections. The review highlighted the biomarker signatures for depression, warranting further investigation.     

Strong preferences of dopamine and l-dopa towards lipid head group: importance of lipid composition and implication for neurotransmitter metabolism

The interactions of the neurotransmitter dopamine, and its precursor l-dopa, with membrane lipids were investigated through a set of molecular dynamic simulations with all atom resolution. The results obtained indicate that both dopamine and l-dopa have a pronounced association with the lipid head groups, predominantly mediated through H-bonds. As a result the molecules are anchored to the interfacial region of the membrane. The strength of this interaction is dependent on lipid composition - the presence of phosphatidylserine leads to an increase in the strength of this interaction, resulting in an H-bond network with a lifetime much longer than the timescale of our simulations. Also, bilayers that include sphingomieline and cholesterol interact strongly with dopamine and l-dopa. We postulate that the high membrane association that we have observed for both dopamine and l-dopa could have the following effects: 1) when on the plasma membrane exterior, favour the availability of these compounds for cell membrane uptake processes and, 2) when on an internal membrane surface, accentuate the importance of membrane-bound metabolizing enzymes over their soluble counterparts.     

Protein synthesis within dendrites: Ionic and neurotransmitter modulation of synthesis of particular polypeptides characterized by gel electrophoresis

This study evaluates whether physiological variables differentially affect the local synthesis of protein constituents of synapses in subcellular fractions containing pinched-off dendrites (synaptodendrosomes). Synaptodendrosomes were pulse-labeled in a medium containing³⁵S-methionine with 3 or 25 mM KCl and in the presence or absence of 0.5 mM EGTA or 10 μM glutamate. Synaptodendrosomes were then subfractionated to prepare synaptic plasma membranes and synaptic junctional complexes. The protein constituents of the synaptic plasma membrane and synaptic junctional complex fractions that were locally synthesized were identified using SDS-PAGE and two-dimensional gel electrophoresis and the extent of labeling of individual bands was analyzed using a Phosphorimager. Analysis of incorporation into individual bands resolved by SDS-PAGE revealed that depolarizing conditions (25 mM KCl) increased the extent of labeling of different bands to a different extent (ranging from 10–70% increases in labeling). Addition of 0.5 mM EGTA decreased the extent of labeling of the same group of bands in both 3 mM KCl and 25 mM KCl conditions. Addition of 10 μM glutamate reduced incorporation especially in the synaptodendrosomes incubated in 25 mM KCl. Two-dimensional gel electrophoresis analyses revealed that the labeled spots that showed differential labeling under the different conditions did not correspond to the most prominent Coomassie-stained spots. These results indicate that the proteins that are synthesized in synaptodendrosomes and regulated by physiological variables are not amongst the more abundant protein constituents of the fractions. Taken together, these results are consistent with the idea that protein synthesis within dendrites may be regulated by synaptic activity.     

"On" and "Off" Responses of K+-Induced Synaptosomal Proline Release: Involvement of the Sodium Pump

The K+-induced release of the putative neurotransmitter proline in rat cerebral cortex synaptosomes was studied by measuring [5-3H]proline released upon exposure to high-K+ media. In contrast to previous experiments, K+ was not substituted for Na+, which was held constant. Under the resulting conditions of increased osmolarity, two peaks of proline release were obtained, one upon exposure to increased [K+], another upon restoring normal [K+]. The dependence of the latter peak on ionic composition of the medium, and its sensitivity to ouabain are discussed.