16 research outputs found
Neuropharmacogenetics of Major Depression: Has the Time Come to Take both Sexes into Account?
Pollution & threats to the environmen
Forced swim test induces divergent global transcriptomic alterations in the hippocampus of high versus low novelty-seeker rats
BACKGROUND: Many neuropsychiatric disorders, including stress-related mood disorders, are complex multi-parametric syndromes. Susceptibility to stress and depression is individually different. The best animal model of individual differences that can be used to study the neurobiology of affect regards spontaneous reactions to novelty. Experimentally, when naive rats are exposed to the stress of a novel environment, they display a highly variable exploratory activity and are classified as high or low responders (HR or LR, respectively). Importantly, HR and LR rats do not seem to exhibit a substantial differentiation in relation to their ‘depressive-like’ status in the forced swim test (FST), a widely used animal model of ‘behavioral despair’. In the present study, we investigated whether FST exposure would be accompanied by phenotype-dependent differences in hippocampal gene expression in HR and LR rats. RESULTS: HR and LR rats present a distinct behavioral pattern in the pre-test session but develop comparable depressive-like status in the second FST session. At 24 h following the second FST session, HR and LR rats (stressed and unstressed controls) were sacrificed and hippocampal samples were independently analyzed on whole rat genome Illumina arrays. Functional analysis into pathways and networks was performed using Ingenuity Pathway Analysis (IPA) software. Notably, hippocampal gene expression signatures between HR and LR rats were markedly divergent, despite their comparable depressive-like status in the FST. These molecular differences are reflected in both the extent of transcriptional remodeling (number of significantly changed genes) and the types of molecular pathways affected following FST exposure. A markedly higher number of genes (i.e., 2.28-fold) were statistically significantly changed following FST in LR rats, as compared to their HR counterparts. Notably, genes associated with neurogenesis and synaptic plasticity were induced in the hippocampus of LR rats in response to FST, whereas in HR rats, FST induced pathways directly or indirectly associated with induction of apoptotic mechanisms. CONCLUSIONS: The markedly divergent gene expression signatures exposed herein support the notion that the hippocampus of HR and LR rats undergoes distinct transcriptional remodeling in response to the same stress regimen, thus yielding a different FST-related ‘endophenotype’, despite the seemingly similar depressive-like phenotype
The Crocus sativus Compounds trans-Crocin 4 and trans-Crocetin Modulate the Amyloidogenic Pathway and Tau Misprocessing in Alzheimer Disease Neuronal Cell Culture Models
Crocus sativus L. natural compounds have been extensively used in traditional medicine for thousands of years. Recent research evidence is now emerging in support of its therapeutic potential for different pathologies including neurodegenerative diseases. Herein, the C. sativus L. natural compounds trans-crocin 4 and trans-crocetin were selected for in depth molecular characterization of their potentially protective effects against Alzheimer’s Disease (AD), utilizing two AD neuronal cell culture models (SH-SY5Y overexpressing APP and PC12 expressing hyperphosphorylated tau). Biologically relevant concentrations, ranging from 0.1 μM to 1 mM, applied for 24 h or 72 h, were well tolerated by differentiated wild type SH-SY5Y and PC12 cells. When tested on neuronally differentiated SH-SY5Y-APP both trans-crocin 4 and trans-crocetin had significant effects against amyloidogenic pathways. Trans-crocin 4 significantly decreased of β-secretase, a key enzyme of the amyloidogenic pathway, and APP-C99, while it decreased γ-secretases that generate toxic beta-amyloid peptides. Similarly, trans-crocetin treatment led to a reduction in β- and γ-secretases, as well as to accumulation of cellular AβPP. When tested on the neuronally differentiated PC12-htau cells, both compounds proved effective in suppressing the active forms of GSK3β and ERK1/2 kinases, as well as significantly reducing total tau and tau phosphorylation. Collectively, our data demonstrate a potent effect of trans-crocin 4 and trans-crocetin in suppressing key molecular pathways of AD pathogenesis, rendering them a promising tool in the prevention and potentially the treatment of AD
8 Neuropharmacogenetics of Major Depression: Has the Time Come to Take both Sexes into Account?
Chapter Neuropharmacogenetics of Major Depression: Has the Time Come to Take both Sexes into Account?
Pollution & threats to the environmen
Histamine Involvement in Visual Development and Adaptation
PURPOSE. This study evaluated the level of histamine in the interaction
between the environment and the visual system during lifespan
development, exploring potential sex differences.
METHODS. Male and female Wistar rats, reared in standard laboratory or
enriched-environment cages from birth to prepuberty or adulthood, were
sacrificed during the critical period for visual development at
postnatal day (P) 25 (P25) or in adulthood at P90. Additionally, animals
born in standard conditions were exposed to an enriched environment at
P90 and sacrificed at P150. The optic chiasm and the visual cortex were
dissected out and tissue histamine was quantified fluorophotometrically.
Statistical analyses were performed by ANOVA.
RESULTS. Histamine levels in the optic chiasm were higher in male than
in female rats at all ages. Comparable sex differences in the visual
cortex were observed only during prepuberty. Basal histamine content in
the optic chiasm was higher in prepuberty and decreased in adulthood in
a sex-independent manner. Exposure to an enriched environment decreased
optic chiasm histamine levels in both sexes and resulted in no sex
difference in the cortical histamine levels at any age. Increased amine
levels were detected in the optic chiasm of female rats exposed to an
enriched environment during adulthood.
CONCLUSIONS. This study presents first evidence associating central
histamine levels with the visual system development and environmental
adaptation, thus providing the lead for the investigation of the
hitherto elusive role of histamine in the regulation of visual
processes. Furthermore, the findings challenge the impact of laboratory
animal raising environments in developmental and behavioral studies.
(Invest Ophthalmol Vis Sci. 2012; 53: 7498-7503)
DOI:10.1167/iovs.12-1080
Individual differences in the effects of cannabinoids on motor activity, dopaminergic activity and DARPP-32 phosphorylation in distinct regions of the brain
Interleukin-1 alpha and beta, TNF-alpha and HTTLPR gene variants study on alcohol toxicity and detoxitication outcome
Genetic factors may influence the liability to treatment outcome and
medical complications in alcoholism. In the present study we
investigated the IL-1A rs 1800587, IL-1B rs3087258, TNF-alpha rs 1799724
and the HTTLPR variants in a sample of 64 alcohol dependents and 47
relatives versus a set of clinical parameters and outcome measures.
Alcohol dependents had a less favorable clinical profile compared to
relatives (higher cholesterol, triglycerides, glucose, glutamic
oxaloacetic transaminase, glutamic pyruvic transaminase,
gamma-glutamyltransferase). After detoxification, all clinical indexes
improved and hepatic enzyme levels were similar in alcohol dependents
and relatives, except for the GGT that remained significantly higher in
alcohol dependents. Alcoholic depressive and anxiety scores were
significantly reduced after detoxification. IL-1A, IL- 1B, TNF-alpha and
HTTLPR variants were not associated with any baseline clinical index or
change after detoxification. In our sample IL-1A, IL-1B, TNF-alpha and
HTTLPR do not appear as liability factors for alcohol toxicity or
detoxification outcome, however the small sample size may influence the
observed results. (c) 2006 Published by Elsevier Ireland Ltd