Neuroscience
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Neurons containing the neuronal nitric oxide synthase (nNOS) enzyme are located in brain areas related to defensive behavior, such as the ventromedial prefrontal cortex (vMPFC). Rats exposed to a live predator (a cat) present anxiety-like behavior and an increased number of nNOS-positive neurons in this brain area one-week later. Moreover, stress-related behavioral changes in rodents can be prevented by systemic or local vMPFC nNOS inhibition. ⋯ Moreover, open-arm exploration of the EPM was negatively correlated with nNOS expression (p<0.05) and NOx levels (p<0.05) in the PL. The anxiogenic-like effect observed 24h after RS was prevented by NPLA (p<0.05). Our results suggest that RS-induced anxiogenic-like effect might depend on increased nNOS-mediated signaling in the PL MPFC.
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The weaver mouse, is a phenocopy of Parkinson's disease (PD) in which dopaminergic neurons degenerate gradually during development, reaching at P21 a neurodegeneration of 55%. Thus, the weaver mouse constitutes an appropriate in vivo PD model for investigating the effect of neuroprotective agents. In the present study, long-term treatment (from P1 to P21) with 17β-estradiol (17β-estradiol) significantly protected the dopaminergic neurons in the substantia nigra (SN) of weaver mouse by 54%, as was detected by immunohistochemical experiments, using the specific antibody against tyrosine hydroxylase (TH). ⋯ Our results show the in vivo neuroprotective effect of 17β-estradiol, which is strongly enhanced by co administration of NAC, indicating a strong synergistic effect of the two drugs. Furthermore, the main mechanism underlying this neuroprotective action seems to be the reversal of the oxidative stress shown by the high peroxidation levels. These results could be of clinical relevance since both drugs are already used separately in the clinic, 17β-estradiol for treatment of PD and NAC as a mucolytic agent and for the treatment of several disorders.
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Women are more likely than men to suffer from anxiety disorders and major depression. These disorders share hyperresponsiveness to stress as an etiological factor. Thus, sex differences in brain arousal systems and their regulation by chronic stress may account for the increased vulnerability to these disorders in women. ⋯ The ovarian steroids could "buffer" the effect of this adverse experience in females on these parameters. Finally, the dexamethasone (DEX) suppression test indicated that the chronic stress associated with social isolation impairs feedback inhibition in both sexes in which an increase in the abundance of glucocorticoid receptors (GRs) in the hippocampus was found. Altogether, these results demonstrate that social isolation affects neuroendocrine reactivity to stress, plasticity and emotionality in a sexually dimorphic manner.
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Prenatal stress and overexposure to glucocorticoids (GC) during development may be associated with an increased susceptibility to a number of diseases in adulthood including neuropsychiatric disorders, such as depression and anxiety. In animal models, prenatal overexposure to GC results in hyper-responsiveness to stress in adulthood, and females appear to be more susceptible than males. Here, we tested the hypothesis that overexposure to GC during fetal development has sex-specific programming effects on the brain, resulting in altered behaviors in adulthood. ⋯ Prenatal DEX increased TpH2 mRNA selectively in the female caudal DRN at P7, whereas it decreased TpH2 mRNA selectively in the female caudal DRN in adulthood. In animals challenged with restraint stress in adulthood, TpH2 mRNA was significantly lower in rostral DRN of prenatal DEX-treated females compared to vehicle-treated females. These data demonstrated that prenatal overexposure to GC alters the development of TpH2 gene expression and these alterations correlated with lasting behavioral changes found in adult female offspring.
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In order to decipher the disease etiology, progression and treatment of multifactorial human brain diseases we utilize a host of different experimental models. Recently, patient-derived human dermal fibroblast (HDF) cultures have re-emerged as promising in vitro functional system for examining various cellular, molecular, metabolic and (patho)physiological states and traits of psychiatric disorders. ⋯ These reports unequivocally prove that signal transduction, redox homeostasis, circadian rhythms and gene*environment (G*E) interactions are all amenable for assessment by the HDF model. Furthermore, the reported findings suggest that this underutilized patient biomaterial, combined with modern molecular biology techniques, may have both diagnostic and prognostic value, including prediction of response to therapeutic agents.