The Reversible Carnitine Palmitoyltransferase 1 Inhibitor (Teglicar) Ameliorates the Neurodegenerative Phenotype in a Drosophila Huntington's Disease Model by Acting on the Expression of Carnitine-Related Genes.

Huntington's disease (HD) is a dramatic neurodegenerative disorder caused by the abnormal expansion of a CAG triplet in the huntingtin gene, producing an abnormal protein. As it leads to the death of neurons in the cerebral cortex, the patients primarily present with neurological symptoms, but recently metabolic changes resulting from mitochondrial dysfunction have been identified as novel pathological features. The carnitine shuttle is a complex consisting of three enzymes whose function is to transport the long-chain fatty acids into the mitochondria. Here, its pharmacological modification was used to test the hypothesis that shifting metabolism to lipid oxidation exacerbates the HD symptoms. Behavioural and transcriptional analyses were carried out on HD Drosophila model, to evaluate the involvement of the carnitine cycle in this pathogenesis. Pharmacological inhibition of CPT1, the rate-limiting enzyme of the carnitine cycle, ameliorates the HD symptoms in Drosophila, likely acting on the expression of carnitine-related genes.

Enriched Environment Increases PCNA and PARP1 Levels in Octopus vulgaris Central Nervous System: First Evidence of Adult Neurogenesis in Lophotrochozoa.

Organisms showing a complex and centralized nervous system, such as teleosts, amphibians, reptiles, birds and mammals, and among invertebrates, crustaceans and insects, can adjust their behavior according to the environmental challenges. Proliferation, differentiation, migration, and axonal and dendritic development of newborn neurons take place in brain areas where structural plasticity, involved in learning, memory, and sensory stimuli integration, occurs. Octopus vulgaris has a complex and centralized nervous system, located between the eyes, with a hierarchical organization. It is considered the most "intelligent" invertebrate for its advanced cognitive capabilities, as learning and memory, and its sophisticated behaviors. The experimental data obtained by immunohistochemistry and western blot assay using proliferating cell nuclear antigen and poli (ADP-ribose) polymerase 1 as marker of cell proliferation and synaptogenesis, respectively, reviled cell proliferation in areas of brain involved in learning, memory, and sensory stimuli integration. Furthermore, we showed how enriched environmental conditions affect adult neurogenesis.

Role of olfaction in Octopus vulgaris reproduction.

The olfactory system in any animal is the primary sensory system that responds to chemical stimuli emanating from a distant source. In aquatic animals "Odours" are molecules in solution that guide them to locate food, partners, nesting sites, and dangers to avoid. Fish, crustaceans and aquatic molluscs possess sensory systems that have anatomical similarities to the olfactory systems of land-based animals. Molluscs are a large group of aquatic and terrestrial animals that rely heavily on chemical communication with a generally dispersed sense of touch and chemical sensitivity. Cephalopods, the smallest class among extant marine molluscs, are predators with high visual capability and well developed vestibular, auditory, and tactile systems. Nevertheless they possess a well developed olfactory organ, but to date almost nothing is known about the mechanisms, functions and modulation of this chemosensory structure in octopods. Cephalopod brains are the largest of all invertebrate brains and across molluscs show the highest degree of centralization. The reproductive behaviour of Octopus vulgaris is under the control of a complex set of signal molecules such as neuropeptides, neurotransmitters and sex steroids that guide the behaviour from the level of individuals in evaluating mates, to stimulating or deterring copulation, to sperm-egg chemical signalling that promotes fertilization. These signals are intercepted by the olfactory organs and integrated in the olfactory lobes in the central nervous system. In this context we propose a model in which the olfactory organ and the olfactory lobe of O. vulgaris could represent the on-off switch between food intake and reproduction.

Mitochondrial ribosomal protein genes connected with Alzheimer's and tellurite toxicity.

Mitochondrial diseases are a group of genetic disorders characterized by dysfunctional mitochondria. Within eukaryotic cells, mitochondria contain their own ribosomes, which synthesize small amounts of proteins, all of which are essential for the biogenesis of the oxidative phosphorylation system. The ribosome is an evolutionarily conserved macromolecular machine in nature both from a structural and functional point of view, universally responsible for the synthesis of proteins. Among the diseases afflicting humans, those of ribosomal origin - either cytoplasmic ribosomes (80S) or mitochondrial ribosomes (70S) - are relevant. These are inherited or acquired diseases most commonly caused by either ribosomal protein haploinsufficiency or defects in ribosome biogenesis. Here we review the scientific literature about the recent advances on changes in mitochondrial ribosomal structural and assembly proteins that are implicated in primary mitochondrial diseases and neurodegenerative disorders, and their possible connection with metalloid pollution and toxicity, with a focus on MRPL44, NAM9 (MNA6) and GEP3 (MTG3), whose lack or defect was associated with resistance to tellurite. Finally, we illustrate the suitability of yeast Saccharomyces cerevisiae (S. cerevisiae) and the nematode Caenorhabditis elegans (C. elegans) as model organisms for studying mitochondrial ribosome dysfunctions including those involved in human diseases.

L-Carnitine in Drosophila: A Review.

L-Carnitine is an amino acid derivative that plays a key role in the metabolism of fatty acids, including the shuttling of long-chain fatty acyl CoA to fuel mitochondrial ß-oxidation. In addition, L-carnitine reduces oxidative damage and plays an essential role in the maintenance of cellular energy homeostasis. L-carnitine also plays an essential role in the control of cerebral functions, and the aberrant regulation of genes involved in carnitine biosynthesis and mitochondrial carnitine transport in Drosophila models has been linked to neurodegeneration. Drosophila models of neurodegenerative diseases provide a powerful platform to both unravel the molecular pathways that contribute to neurodegeneration and identify potential therapeutic targets. Drosophila can biosynthesize L-carnitine, and its carnitine transport system is similar to the human transport system; moreover, evidence from a defective Drosophila mutant for one of the carnitine shuttle genes supports the hypothesis of the occurrence of ß-oxidation in glial cells. Hence, Drosophila models could advance the understanding of the links between L-carnitine and the development of neurodegenerative disorders. This review summarizes the current knowledge on L-carnitine in Drosophila and discusses the role of the L-carnitine pathway in fly models of neurodegeneration.

Corrigendum: Magnitude Assessment of Adult Neurogenesis in the Octopus vulgaris Brain Using a Flow Cytometry-Based Technique.

[This corrects the article DOI: 10.3389/fphys.2018.01050.].

Magnitude Assessment of Adult Neurogenesis in the Octopus vulgaris Brain Using a Flow Cytometry-Based Technique.

Adult neurogenesis is widespread among metazoans, it occurs in animals with a network nervous system, as cnidarians, and in animals with a complex and centralized brain, such as mammals, non-mammalian vertebrates, ecdysozoans, and a lophotrochozoan, Octopus vulgaris. Nevertheless, there are important differences among taxa, especially in the number of the regions involved and in cell proliferation rate during the life-cycle. The comparative evaluation of adult neurogenesis among different brain regions is an arduous task to achieve with only stereological techniques. However, in Octopus vulgaris we recently confirmed the presence of active proliferation in the learning-memory centers, multisensory integration centers, and the motor centers of the adult brain. Here, using a flow cytometry technique, we provide a method to quantify the active proliferation in octopus nervous system using a BrdU in vitro administration without exposing the animals to stress or painful injections usually used. This method is in line with the current animal welfare regulations regarding cephalopods, and the flow cytometry-based technique enabled us to measure adult neurogenesis more quickly and reliably than histological techniques, with the additional advantage of processing multiple samples in parallel. Flow cytometry is thus an appropriate technique for measuring and comparing adult neurogenesis in animals that are in a different physiological and/or environmental contexts. A BrdU immunoreactivity distribution, to define the neurogenic areas, and the effective penetration in vitro of the BrdU is also provided.

Olfactory organ of Octopus vulgaris: morphology, plasticity, turnover and sensory characterization.

The cephalopod olfactory organ was described for the first time in 1844 by von Kölliker, who was attracted to the pair of small pits of ciliated cells on each side of the head, below the eyes close to the mantle edge, in both octopuses and squids. Several functional studies have been conducted on decapods but very little is known about octopods. The morphology of the octopus olfactory system has been studied, but only to a limited extent on post-hatching specimens, and the only paper on adult octopus gives a minimal description of the olfactory organ. Here, we describe the detailed morphology of young male and female Octopus vulgaris olfactory epithelium, and using a combination of classical morphology and 3D reconstruction techniques, we propose a new classification for O. vulgaris olfactory sensory neurons. Furthermore, using specific markers such as olfactory marker protein (OMP) and proliferating cell nuclear antigen (PCNA) we have been able to identify and differentially localize both mature olfactory sensory neurons and olfactory sensory neurons involved in epithelium turnover. Taken together, our data suggest that the O. vulgaris olfactory organ is extremely plastic, capable of changing its shape and also proliferating its cells in older specimens.