Neuroscience
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Anxiety is considered an important protracted abstinence symptom that can aggravate craving and relapse risk in opioid addicts. Although the insular cortex (IC) has been reported to be a key brain region in mediating emotional and motivational alterations induced by drug consumption and withdrawal, the role of IC in anxiety related to protracted abstinence remains elusive. ⋯ Bilateral lesion of the medial IC, but not the anterior or posterior IC with ibotenic acid (IBO) alleviated the anxiety-like behavior. (3) Expression of Wnt7a in the medial IC was significantly increased after 28 days of withdrawal, and specific down-regulation of Wnt7a with AAV-shWnt7a also alleviated the anxiety-like behavior. The findings reveal the medial IC is involved in mediating anxiety-like behavior related to morphine protracted abstinence, in which Wnt7a plays a critical role.
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Alzheimer's disease (AD) is a progressive neurodegenerative disorder, with no effective method for its treatment so far. The pathogenesis of AD has been reported, but the endogenous metabolic profile and disease-related biomarkers are still not clear. To better understand AD, an AD model induced by injecting β-amyloid 25-35 (Aβ 25-35) solution into bilateral hippocampus was developed on Sprague-Dawley rats. ⋯ The results showed that compared with healthy control rats, AD rats suffered from cognitive dysfunction, hippocampus damage, Aβ formation and tau phosphorylation at 8 weeks after surgery, suggesting that the Aβ25-35-induced AD model was successfully established. In addition, the levels of γ-aminobutyric acid, acetylcholine, glycine, norepinephrine, serotonin, taurine and dopamine decreased and glutamate and aspartic acid increased in hippocampal tissue of AD rats. 45 altered metabolites mainly involved in 8 metabolic pathways were identified as the endogenous biomarkers of AD. According to the analysis of the biological significance of metabolic profiles, the pathogenesis of AD was mainly due to gut microbiome dysbiosis, inhibition of energy metabolism, oxidative stress injury and loss of neuronal protective substances.
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Huntingtin-associated protein 1 (HAP1) is a neural interactor of huntingtin in Huntington's disease and interacts with gene products in a number of other neurodegenerative diseases. In normal brains, HAP1 is expressed abundantly in the hypothalamus and limbic-associated regions. These areas tend to be spared from neurodegeneration while those with little HAP1 are frequently neurodegenerative targets, suggesting its role as a protective factor against apoptosis. ⋯ HAP1-immunoreactive (ir) cells were classified into five discrete groups: (1) a distinct retrosplenial cell cluster exclusive to the superficial layers of the granular cortex, (2) a conspicuous, thin line of cells in layers IV/V of the "subiculum-backing cortex," (3) a group of highly immunoreactive cells associated with the medial entorhinal-subicular corner, (4) pericallosal cells just below layer VI and adjacent to the white matter, and (5) other sporadic, widely-disseminated HAP1-immunoreactive cells. HAP1 was found to be the first marker for the complex subiculum-backing cortex and a precise marker for several subfields in the retrosplenial-retrohippocampal area, verified through comparative staining with other neurochemicals. HAP1 may play an important role in protecting these cortical structures and functions for higher nervous activity by increasing the threshold to neurodegeneration and decreasing vulnerability to stress or aging.
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The serotoninergic 5-HT2A receptor is involved in the mechanism of depression and antidepressant drugs action. Earlier we showed that striatal-enriched protein tyrosine phosphatase (STEP) inhibitor - 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (TC-2153) affects both the brain serotoninergic system and the brain-derived neurotropic factor that are known to be involved in the psychopathology of depression. In the present study we investigated the effects of chronic TC-2153 administration on behavior in the standard battery of tests as well as the effects of acute and chronic TC-2153 treatment on the brain 5-HT2A receptors in mice. ⋯ Moreover, both acute and chronic TC-2153 administration inhibited the functional activity of 5-HT2A receptors estimated by the number of 2,5-dimethoxy-4-iodoamphetamine (DOI, agonist of 5-HT2A receptors)-induced head-twitches. TC-2153 treatment also attenuated the DOI-induced c-fos expression in cortical and hippocampal neurons and reduced the 5-HT2A receptor protein level in the hippocampus and frontal cortex, but not in the striatum. Taken together, our combined data demonstrate that the antidepressant effect of STEP inhibitor TC-2153 could be mediated by its inhibitory properties towards the 5-HT2A receptor-mediated signaling.
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The ability to recognize a tool's affordances (how a spoon should be appropriately grasped and used), is vital for daily life. Prior research has identified parietofrontal circuits, including mirror neurons, to be critical in understanding affordances. However, parietofrontal action-encoding regions receive extensive visual input and are adjacent to parietofrontal attention control networks. ⋯ Particularly, only overt gaze toward the hand-tool interaction engaged mirror neurons (frontal N400) when discerning grasps that manipulate but not functionally use a tool - (grasp bowl rather than stem of spoon). Results here detail the first human electrophysiological evidence on how attention selectively modulates multiple parietofrontal grasp-perception circuits, especially the mirror neuron system, while unaffecting parietofrontal encoding of tool-use contexts. These results are pertinent to neurophysiological models of affordances that typically neglect the role of attention in action perception.