ABSTRACT
Acute stress is an important factor in the development of anxiety disorders. Zebrafish are an organism model widely used by studies that aim to describe the events in the brain that control stress-elicited anxiety. The goal of the current study was to evaluate the pattern of cell activation in the telencephalon of adult zebrafish and the role of the GABAergic system on the modulation of anxiety-like behavior evoked by acute restraint stress. Zebrafish that underwent acute restraint stress presented decreased expression of the c-fos protein in their telencephalon as well as a significant decrease in GABA release. The data also supports that decreased GABA levels in zebrafish brains have diminished the activation of GABAA receptors eliciting anxiety-like behavior. Taken together these findings have helped clarify a neurochemical pathway controlling anxiety-like behavior evoked by acute stress in zebrafish while also opening the possibility of new perspective opportunities to use zebrafish as an animal model to test anxyolitic drugs that target the GABAergic system.
Subject(s)
Receptors, GABA-A/metabolism , Stress, Psychological/metabolism , Telencephalon/metabolism , gamma-Aminobutyric Acid/metabolism , Animals , Behavior, Animal , Disease Models, Animal , Glutamic Acid/metabolism , Signal Transduction , ZebrafishABSTRACT
OBJECTIVE: The recognition of the limits between normal and pathological aging is essential to start preventive actions. The aim of this paper is to compare the Cambridge Neuropsychological Test Automated Battery (CANTAB) and language tests to distinguish subtle differences in cognitive performances in two different age groups, namely young adults and elderly cognitively normal subjects. METHOD: We selected 29 young adults (29.9±1.06 years) and 31 older adults (74.1±1.15 years) matched by educational level (years of schooling). All subjects underwent a general assessment and a battery of neuropsychological tests, including the Mini Mental State Examination, visuospatial learning, and memory tasks from CANTAB and language tests. Cluster and discriminant analysis were applied to all neuropsychological test results to distinguish possible subgroups inside each age group. RESULTS: Significant differences in the performance of aged and young adults were detected in both language and visuospatial memory tests. Intragroup cluster and discriminant analysis revealed that CANTAB, as compared to language tests, was able to detect subtle but significant differences between the subjects. CONCLUSION: Based on these findings, we concluded that, as compared to language tests, large-scale application of automated visuospatial tests to assess learning and memory might increase our ability to discern the limits between normal and pathological aging.
Subject(s)
Aging , Cognition Disorders/diagnosis , Intelligence Tests , Language Tests , Adult , Aged , Aging/physiology , Aging/psychology , Brazil , Cluster Analysis , Cognition , Cognition Disorders/prevention & control , Cross-Sectional Studies , Early Diagnosis , Educational Status , Female , Humans , Male , Memory , Neuropsychological Tests , Spatial Learning/physiology , Spatial Navigation/physiology , Task Performance and AnalysisABSTRACT
A major hindrance for the development of psychiatric drugs is the prediction of how treatments can alter complex behaviors in assays which have good throughput and physiological complexity. Here we report the development of a medium-throughput screen for drugs which alter anxiety-like behavior in adult zebrafish. The observed phenotypes were clustered according to shared behavioral effects. This barcoding procedure revealed conserved functions of anxiolytic, anxiogenic and psychomotor stimulating drugs and predicted effects of poorly characterized compounds on anxiety. Moreover, anxiolytic drugs all decreased, while anxiogenic drugs increased, serotonin turnover. These results underscore the power of behavioral profiling in adult zebrafish as an approach which combines throughput and physiological complexity in the pharmacological dissection of complex behaviors.
Subject(s)
Anti-Anxiety Agents/pharmacology , Anxiety/drug therapy , Animals , Buspirone/pharmacology , Caffeine/pharmacology , Diazepam/pharmacology , Drug Evaluation, Preclinical , Freezing Reaction, Cataleptic/drug effects , Serotonin/metabolism , Swimming , ZebrafishABSTRACT
Nitric oxide (NO) is a highly reactive gas with considerable diffusion power that is produced pre- and post synaptically in the central nervous system (CNS). In the visual system, it is involved in the processing of the visual information from the retina to superior visual centers. In this review we discuss the main mechanisms through which nitric oxide acts, in physiological levels, on the retina, lateral geniculate nucleus (LGN) and primary visual cortex. In the retina, the cGMP-dependent nitric oxide activity initially amplifies the signal, subsequently increasing the inhibitory activity, suggesting that the signal is "filtered". In the thalamus, on dLGN, neuronal activity is amplified by NO derived from brainstem cholinergic cells, in a cGMP-independent mechanism; the result is the amplification of the signal arriving from retina. Finally, on the visual cortex (V1), NO acts through changes on the cGMP levels, increasing signal detection. These observations suggest that NO works like a filter, modulating the signal along the visual pathways.
Subject(s)
Nitric Oxide/metabolism , Retina/physiology , Retinal Ganglion Cells/metabolism , Vision, Ocular/physiology , Visual Cortex/metabolism , Animals , Cyclic GMP/metabolism , Gene Expression Regulation , Geniculate Bodies/metabolism , Glutamine/metabolism , Humans , N-Methylaspartate/metabolism , Neurons/metabolism , Retina/metabolism , Signal Transduction , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolismABSTRACT
The present study describes a simple and efficient method utilizing high performance liquid chromatography (HPLC) coupled to fluorescence detection for the determination of kinetic parameters of glutamate uptake in nervous tissue. Retinal tissue obtained from 7-day-old chicks was incubated with known concentrations of glutamate (50-2000 µM) for 10 min, and the levels of the o-phtaldehyde (OPA)-derivatized neurotransmitter in the incubation medium were measured. By assessing the difference between initial and final concentrations of glutamate in the medium, a saturable uptake mechanism was characterized (K(m)=8.2 and V(max)=9.8 nmol/mg protein/min). This measure was largely sodium- and temperature-dependent, strongly supporting that the mechanism for concentration decrements is indeed uptake by high-affinity transporters. Added to this, our results also demonstrated that zinc chloride (an inhibitor of glutamate/aspartate transporters) evoked a concentration-dependent decrease in glutamate uptake, demonstrating the specificity of our methodology. Overall, the present work characterizes an alternative methodology to evaluate glutamate uptake in nervous tissue using HPLC. This approach could be an important tool for studies associated to the characterization of minute alterations in glutamate transport related with central nervous system injury.
