Journal of molecular neuroscience : MN
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A growing body of evidence suggests the existence of a functional interaction between gabapentin (GBP)-morphine system. However, the neuro-anatomical sites and molecular mechanism of action of gabapentin-morphine interaction to prevent and reverse morphine side effects as well as enhancement of the analgesic effect of morphine is not clear. Therefore, we examined the combined effects of GBP-morphine on acute morphine-induced c-Fos expression in rat nucleus accumbens. ⋯ The present study demonstrated that, administration of GBP (150 mg/kg, i.p.) in combination with morphine (5 mg/kg, i.p.) significantly (p < 0.01) attenuated the acute morphine (5 mg/kg, i.p.)-induced c-Fos expression in the rat nucleus accumbens shell. Present results showed that GBP-morphine combination action prevented the acute morphine-induced c-Fos expression in rat nucleus accumbens. Moreover, this study provides first evidence of neuro-anatomical site and that GBP neutralized the morphine-induced activation of rat nucleus accumbens shell.
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The relationship between β-amyloid (Aβ) and tau is not fully understood, though it is proposed that in the pathogenesis of Alzheimer's disease (AD) Aβ accumulation precedes and promotes tau hyperphosphorylation via activation of glycogen synthase kinase-3beta (GSK-3β). Both events contribute to learning and memory impairments. Modulation of γ-secretase activity has proved to reduce the Aβ burden and cognitive deficits in mouse models of AD, but its ability in reducing the tau pathology remains elusive. ⋯ CHF5074 was more effective than ibuprofen in reducing tau pathology, though both compounds decreased the GSK-3β level and increased the GSK-3β inhibitory phosphorylation near to the non-Tg values. The inhibition of GSK-3β appeared to be secondary to the reduction of Aβ generation as, differently from LiCl, CHF5074 reproduced its effect in hAPP-overexpressing neuroglioma cells, but not in wild-type primary neurons. Our data show that the novel γ-secretase modulator CHF5074 can fully reverse β-amyloid-associated tau pathology, thus representing a promising therapeutic agent for AD.
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The prediction of outcome after ischemic stroke (IS) is currently based on indirect data from clinical and radiological evaluation. We evaluated the usefulness of serum Tau protein as possible prognostic markers for IS. Fifty-six patients with computed tomography-confirmed IS were enrolled. ⋯ Patients in whom Tau protein was detected in serum, when compared with patients without Tau protein, developed more severe neurological deficits, had worse functional status measured in the early and late phase of IS, and were found to have larger volume of infarction. However, Tau protein concentrations measured within the early phase of IS did not correlate with degrees of neurological deficit and disability in the early phase and also after 3 months of IS. Detection of Tau protein in the serum of patients with IS but not its concentration can be considered as a bad prognostic factor for the clinical outcome in early and late phase of IS.
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Anxiety disorders are frequently long-lasting and debilitating for more than 40 million American adults. Although stressor exposure plays an important role in the etiology of some anxiety disorders, the mechanisms by which exposure to stressful stimuli alters central circuits that mediate anxiety-like emotional behavior are still unknown. Substantial evidence has implicated regions of the central extended amygdala, including the bed nucleus of the stria terminalis (BNST) and the central nucleus of the amygdala as critical structures mediating fear- and anxiety-like behavior in both humans and animals. ⋯ Psychoneuroendocrinology 34:833-843, 2009). We describe how interactions between PACAP and CRH in the BNST may mediate stress-associated behaviors, including anorexia and anxiety-like behavior. These studies have the potential to define specific mechanisms underlying anxiety disorders, and may provide important therapeutic strategies for stress and anxiety management.
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Parkinson's disease (PD) is a severe neurodegenerative disorder characterised by loss of dopaminergic neurons of the substantia nigra. The pathological hallmarks are cytoplasmic inclusions termed Lewy bodies consisting primarily of aggregated alpha-synuclein (alphaSN). Different lines of transgenic mice have been developed to model PD but have failed to recapitulate the hallmarks of this disease. ⋯ Rotenone treatment of 30 mg/kg for 25 doses over a 35-day period was tolerated in the transgenic mice and resulted in decreased spontaneous locomotor movement and increased cytoplasmic alphaSN expression. The mitochondrial Parkinson's-associated PTEN-induced kinase 1 protein levels were also increased in transgenic mouse brain after rotenone treatment; there was no change in brain dopamine levels or nigrostriatal cell loss. These hA53T alphaSN transgenic mice provide a useful model for presymptomatic Parkinson's features and are valuable for study of associated compensatory changes in early Parkinson's disease stages.