J.A. Del Rio

Zinc-positive boutons in the cerebral cortex of lizards show glutamate immunoreactivity

SummaryZinc-positive boutons, originating in the medial cortex of lizards, exhibit glutamate immunoreactivity. This finding supports the presumed homology between lizard zinc-positive boutons and the hippocampal mossy fibres of mammals, which are also glutamate-immunoreactive and zinc-positive.Zinc-positive boutons of lizards contain a chelatable pool of zinc located in the synaptic vesicles, as occurs in the hippocampal mossy fibres of mammals. These synaptic systems also contain glutamate, which indicates a possible simultaneous action of zinc and glutamate during synaptic transmission.

The protozoan parasite Perkinsus atlanticus elicits a unique defensive response in the clam Tapes semidecussatus

The venerid clams, Tapes decussatus and T. semidecussatus, develop a singular defensive response to Perkinsus atlanticus infection. This reaction involves the redifferentiation of recruited granulocytes and the expression de novo of the polypeptide p225. To determine whether the association of this defensive process with the natural parasitism by P. atlanticus is unique, the inflammatory response elicited by inoculations of bacteria, algae and non-viable P. atlanticus pre-zoosporangia in the clam T. semidecussatus was shown. Inoculated areas were heavily infiltrated by granulocytes and delimited by myofibroblast-like cells and extracellular matrix. While bacteria and algae were phagocytosed by the infiltrated granulocytes, pre-zoosporangia were not. After 40 days, neither cell redifferentiation nor the expression of p225 was observed. These findings indicate that both redifferentiation and p225 expression are specifically associated with P. atlanticus infection. After 5-bromodeoxyuridine administration, only a few cells were labelled either in the inoculated zone or in the cellular reaction around P. atlanticus meronts. Significant differences between untreated and inoculated groups were observed in the epicardic connective tissue soon after injection. These results suggest that this anatomical region could be the main site of haemocyte proliferation stimulated after inoculation of foreign bodies in T. semidecussatus.

Expression of discoidin domain receptor 1 during mouse brain development follows the progress of myelination.

Discoidin domain receptor 1 is a tyrosine kinase receptor expressed in a variety of tissues including the brain. This study describes mRNA and protein expression of discoidin domain receptor 1 in mouse brain during development and provides new insights into its role during gliogenesis and neurogenesis. We performed in situ hybridization for discoidin domain receptor 1 in mouse brains at embryonic day 18, postnatal days 5, 9, 15, 21 and adulthood and observed a diffuse pattern in the proliferative areas during embryogenesis. From postnatal day 5 onwards, a defined cellular expression pattern of discoidin domain receptor 1 was observed, mainly located in white matter tracts and following a spatio-temporal pattern that overlapped the progress of myelination. Next, we performed double-labeling reactions (in situ hybridization followed by immunohistochemistry) that confirmed that discoidin domain receptor 1 was expressed by mature oligodendrocytes. We observed that cells positive for discoidin domain receptor 1 also expressed carnosine and anti-adenomatous polyposis coli, two mature oligodendrocyte markers. Based on the localization of discoidin domain receptor 1 specifically in the white matter fiber tracts during postnatal development, we suggest that discoidin domain receptor 1 participates in the development and maintenance of the myelin sheath.

Role of PrP C Expression in Tau Protein Levels and Phosphorylation in Alzheimer's Disease Evolution

Alzheimer’s disease (AD) is characterized by the presence of amyloid plaques mainly consisting of hydrophobic β-amyloid peptide (Aβ) aggregates and neurofibrillary tangles (NFTs) composed principally of hyperphosphorylated tau. Aβ oligomers have been described as the earliest effectors to negatively affect synaptic structure and plasticity in the affected brains, and cellular prion protein (PrPC) has been proposed as receptor for these oligomers. The most widely accepted theory holds that the toxic effects of Aβ are upstream of change in tau, a neuronal microtubule-associated protein that promotes the polymerization and stabilization of microtubules. However, tau is considered decisive for the progression of neurodegeneration, and, indeed, tau pathology correlates well with clinical symptoms such as dementia. Different pathways can lead to abnormal phosphorylation, and, as a consequence, tau aggregates into paired helical filaments (PHF) and later on into NFTs. Reported data suggest a regulatory tendency of PrPC expression in the development of AD, and a putative relationship between PrPC and tau processing is emerging. However, the role of tau/PrPC interaction in AD is poorly understood. In this study, we show increased susceptibility to Aβ-derived diffusible ligands (ADDLs) in neuronal primary cultures from PrPC knockout mice, compared to wild-type, which correlates with increased tau expression. Moreover, we found increased PrPC expression that paralleled with tau at early ages in an AD murine model and in early Braak stages of AD in affected individuals. Taken together, these results suggest a protective role for PrPC in AD by downregulating tau expression, and they point to this protein as being crucial in the molecular events that lead to neurodegeneration in AD.

Involvement of Dab1 in APP processing and β-amyloid deposition in sporadic Creutzfeldt–Jakob patients

Alzheimers disease and prion pathologies (e.g., Creutzfeldt-Jakob disease (CJD)) display profound neural lesions associated with aberrant protein processing and extracellular amyloid deposits. Dab1 has been implicated in the regulation of amyloid precursor protein (APP), but a direct link between human prion diseases and Dab1/APP interactions has not been published. Here we examined this putative relationship in 17 cases of sporadic CJD (sCJD) post-mortem. Biochemical analyses of brain tissue revealed two groups, which also correlated with PrP(sc) types 1 and 2. One group with PrP(sc) type 1 showed increased Dab1 phosphorylation and lower betaCTF production with an absence of Abeta deposition. The second sCJD group, which carried PrP(sc) type 2, showed lower levels of Dab1 phosphorylation and betaCTF production, and Abeta deposition. Thus, the present observations suggest a correlation between Dab1 phosphorylation, Abeta deposition and PrP(sc) type in sCJD.

Social defeat leads to changes in the endocannabinoid system: An overexpression of calreticulin and motor impairment in mice.

Prolonged and sustained stimulation of the hypothalamo-pituitary-adrenal axis have adverse effects on numerous brain regions, including the cerebellum. Motor coordination and motor learning are essential for animal and require the regulation of cerebellar neurons. The G-protein-coupled cannabinoid CB1 receptor coordinates synaptic transmission throughout the CNS and is of highest abundance in the cerebellum. Accordingly, the aim of this study was to investigate the long-lasting effects of chronic psychosocial stress on motor coordination and motor learning, CB1 receptor expression, endogenous cannabinoid ligands and gene expression in the cerebellum. After chronic psychosocial stress, motor coordination and motor learning were impaired as indicated the righting reflex and the rota-rod. The amount of the endocannabinoid 2-AG increased while CB1 mRNA and protein expression were downregulated after chronic stress. Transcriptome analysis revealed 319 genes differentially expressed by chronic psychosocial stress in the cerebellum; mainly involved in synaptic transmission, transmission of nerve impulse, and cell-cell signaling. Calreticulin was validated as a stress candidate gene. The present study provides evidence that chronic stress activates calreticulin and might be one of the pathological mechanisms underlying the motor coordination and motor learning dysfunctions seen in social defeat mice.

EPA-1474 – Psychosocial stress and psychiatric phenotypes: endocannabinoids and cannabinoid receptor (CBR) expression in cortico-striatal connectivity

Introduction Aim of study to investigate the consequences of chronic psychosocial stress on behavior, endocannabinoids and CBR expression in prefrontal cortex (PFC) and striatum of mice. Materials And Methods Psychosocial stress was induced in adult C57Bl/6 mice by resident-intruder paradigm (Brzozka et al. 2011). After 3 weeks daily exposure to psychosocial stress for 1 hour, animals were studied during the rodent active phase (night) by behavioral tests such as Functional Observational Battery (FOB), Rota-Rod (R-R), Open Field (OF), Prepulse Inhibition test (PPI). After behavioral testing, mice were sacrificed. 4 mice brains (prefrontal cortex, dorsal striatum) were studied by LC-MS to estimate the concentration of anandamide (AEA), 2- arachidonoylglycerol (2-AG), N-oleoylethanolamine (OEA), palmitoylethanolamide (PEA) (coll. di Marzo). In Situ Hybridization (ISH)and Immunohistochemistry (IHCH) against CB1 receptor were performed on free floating brain coronal sections fixed by 4% paraformaldehyde (coll del Rio). Results 1. After psychosocial stress, mice displayed lower body weight (p Conclusion Chronic psychosocial stress significantly changes behavior, endocannabinoids, CB receptor function and the striatal-cortical connectivity. These changes may contribute to vulnerability for psychosis and addiction.

Axon Guidance and Repulsion. The Molecular Code of Social Life in the Brain

The generation of a functional nervous system is dependent on precise pathfinding of axons during their development. This pathfinding is directed by the distribution of local and long-range guidance cues. Gradients of long-range guidance cues have been associated with growth cone function for over a hundred years, but their developmental roles are still poorly understood. Here we review the developmental roles and the complex intracellular signaling pathways enabling chemoattractive or repulsive axon-guidance molecules like netrins, semaphorins and ephrins to regulate axon growth. Recent research findings suggest that these molecules signal through specific receptors leading to local cytoskeletal rearrangements in the growth cone or cell leading edge; and through intracellular kinases, which have the potential to alter gene expression changes in the developing neuron. In addition, we also summarize the increasing body of knowledge on their roles in the inhibition of axon regeneration after adult lesions in the central and peripheral nervous system.