Neuroscience
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Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disease characterized by the loss of motor neurons in the motor cortex, brain stem and spinal cord. Currently, there is no cure for this lethal disease. Although the mechanism underlying neuronal cell death in ALS remains elusive, growing evidence supports a crucial role of endoplasmic reticulum (ER) stress in the pathogenesis of ALS. ⋯ The results also revealed a significant decrease in the levels of the ER chaperone glucose-regulated protein 78 (BiP/Grp78) and markers of another two ER stress pathways, activating transcription factor 6α (ATF6α) and inositol-requiring enzyme 1 (IRE1). In addition, guanabenz increased the protein levels of anti-apoptotic B cell lymphoma/lewkmia-2 (Bcl-2), and down-regulated the pro-apoptotic protein levels of C/EBP homologous protein (CHOP), Bcl-2-associated X protein (BAX) and cytochrome C in SOD1 G93A mice. Our findings indicate that guanabenz may represent a novel therapeutic candidate for the treatment of ALS, a lethal human disease with an underlying mechanism involving the attenuation of ER stress and mitochondrial stress via prolonging eIF2α phosphorylation.
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Whether beauty and ugliness represent two independent judgement categories or, instead, opposite extremes of a single dimension is a matter of debate. In the present 3T-functional Magnetic Resonance Imaging (fMRI) study, 20 participants were scanned while judging faces and nude bodies of people classified as extremely ugly, extremely beautiful, or indifferent. Certain areas, such as the caudate/nucleus accumbens (NAcc) and the anterior cingulate cortex (ACC), exhibited a linear relationship across esthetic judgments supporting ugliness as the lowest extreme of a beauty continuum. ⋯ This is interpreted as the activation of neural circuits related to self- vs. other-assessment. Beauty and ugliness in the brain, at least in relation to natural and biologically and socially relevant stimuli (faces and bodies), appear tightly related and non-independent. Finally, neutral stimuli elicited strong and wide activations of the somatosensory and somatomotor systems together with longer reaction times and higher error rates, probably reflecting the difficulty of the human brain to classify someone as indifferent.
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Hydrocephalus is caused by the accumulation of cerebrospinal fluid (CSF) in the cerebral ventricular system which results in an enlargement of the cranium due to increased intraventricular pressure. The increase in pressure within the brain typically results in sloughing of ciliated ependymal cells, loss of cortical gray matter, and increased gliosis. Congenital hydrocephalus is associated with several syndromes including primary ciliary dyskinesia (PCD), a rare, genetically heterogeneous, pediatric syndrome that results from defects in motile cilia and flagella. ⋯ Alterations in astrocytosis, microglial activation, myelination, and the neuronal population were identified and are generally more severe on the C57BL/6J background. Analysis of ependymal ciliary clearance ex vivo and CSF flow in vivo demonstrate a physiological defect in nm1054 and bgh mice on both genetic backgrounds, indicating that abnormal cilia-driven flow is not the sole determinant of the severity of hydrocephalus in these models. These results suggest that genetic modifiers play an important role in susceptibility to severe PCD-associated hydrocephalus.
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Cholecystokinin octapeptide (CCK-8), a brain-gut peptide, plays an important role in several opioid addictive behaviors. We previously reported that CCK-8 attenuated the expression and reinstatement of morphine-induced conditioned place preference. The possible effects of CCK-8 on the negative affective components of drug abstinence are not clear. ⋯ Mu-opioid receptor antagonism with CTAP (10 μg, i.c.v.) decreased the 'anxiolytic' effect. CCK-8 inhibited anxiety-like behaviors in morphine-withdrawal rats by up-regulating endogenous opioids via the CCK1 receptor in rats. This study clearly identifies a distinct function of CCK-8 and a potential medication target of central CCK1 receptors for drugs aimed at ameliorating drug addiction.
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Visually-driven actions and perception are traditionally ascribed to the dorsal and ventral visual streams of the cortical processing hierarchy. However, motion perception and the control of tracking eye movements both depend on sensory motion analysis by neurons in the dorsal stream, suggesting that the same sensory circuits may underlie both action and perception. Previous studies have suggested that multiple sensory modules may be responsible for the perception of low- and high-level motion, or the detection versus identification of motion direction. ⋯ We determined perceptual-oculomotor correlations across observers, defined as the correlation between each observer's mean perceptual precision and mean oculomotor precision. Across observers, we found that: (i) mean perceptual precision was correlated between the two tasks; (ii) mean oculomotor precision was correlated between the tasks, and (iii) oculomotor and perceptual precision were correlated for volitional smooth pursuit, but not reflexive ocular following. Collectively, these results demonstrate that sensory circuits with common neuronal constraints subserve motion perception and volitional, but not reflexive eye movements.