Neuroscience
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Apoptosis is a major form of cell death in cerebral ischemia/reperfusion (I/R) pathogenesis and may represent a target for treatment. Diosmin (DM), a micronized purified flavonoid drug, possesses an anti-apoptotic effect in the treatment of varicose veins and renal injury. However, the effect of DM in the acute phase of cerebral I/R is not clear. This study investigated DM's role in cerebral I/R and its potential mechanism. ⋯ These results showed that DM protected against cerebral I/R injury through activating JAK2/STAT3 signal pathway.
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Shape perception can be achieved based on various cues such as luminance, color, texture, depth and motion. To investigate common neural mechanisms underlying shape perception cued by various visual attributes, we examined single-neuron activity in the monkey anterior superior temporal sulcus (STS) in response to shapes defined by luminance and motion cues during shape discrimination. We found cortical mapping with respect to selectivity for shapes as well as for direction of motion in the STS. ⋯ They showed a highly similar shape preference between the different visual attributes, indicating cue-invariant shape selectivity. The cue-invariant shape-selectivity was modulated with target selection as well as with discrimination performance of monkeys. These results suggest that lSTS could be involved in cue-invariant shape discrimination, but not the uSTS.
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Leucine-rich repeat in Flightless-1 interaction protein 1 (Lrrfip1) is an up-regulated protein after cerebral ischemia whose precise role in the brain both in healthy and ischemic conditions is unclear. Different Lrrfip1 isoforms with distinct roles have been reported in human and mouse species. The present study aimed to analyze the Lrrfip1 transcriptional variants expressed in rat cortex, to characterize their expression patterns and subcellular location after ischemia, and to define their putative role in the brain. ⋯ The main isoform, Lrrfip1, was found to be up-regulated from the acute to the late phases of ischemia in the cytoplasm of neurons and astrocytes of the peri-infarct area. This study demonstrates that Lrrfip1 activates β-catenin, Akt, and mammalian target of rapamycin (mTOR) proteins in astrocytes and positively regulates the expression of the excitatory amino acid transporter subtype 2 (GLT-1). Our findings point to Lrrfip1 as a key brain protein that regulates pro-survival pathways and proteins and encourages further studies to elucidate its role in cerebral ischemia as a potential target to prevent brain damage and promote functional recovery after stroke.
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Depression is a common symptom in Parkinson's disease (PD), but its pathophysiology remains unclear. Several lines of studies have revealed that the prelimbic (PrL) sub-region of the ventral medial prefrontal cortex and 5-HT1A receptors are involved in the regulation of depression. In this study, we examined whether complete unilateral lesions of the medial forebrain bundle (MFB) using 6-hydroxydopamine in rats are able to induce depressive-like behaviors, the role of PrL 5-HT1A receptors in the regulation of these behaviors, and co-localization of 5-HT1A receptor and neuronal glutamate transporter EAAC1-immunoreactive (EAAC1-ir) neurons in the PrL. ⋯ Furthermore, the intra-PrL injection of 5HT1A receptor antagonist WAY-100635 (60, 120, and 240ng/rat) showed a decrease in sucrose consumption, and an increase in immobility time, indicating the induction of depressive-like responses. However, the effective doses in the lesioned rats were higher than those in sham-operated rats, which attribute to down-regulation of 5-HT1A receptor expression on EAAC1-ir neurons in the PrL of the lesioned rats. These findings suggest that unilateral lesions of the MFB in rats may induce depressive-like behaviors, and 5-HT1A receptors of the PrL play an important role in the regulation of these behaviors.
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Inflammation, oxidative and nitrosative stress underlie depression being assessed in rodents by the systemic administration of lipopolysacharide (LPS). There is an increasing body of evidence of an involvement of nitric oxide (NO) pathway in depression, but this issue was not investigated in LPS-induced model. Thus, herein we evaluated the effects of NO-pathway-modulating drugs, named aminoguanidine, l-NAME, sildenafil and l-arginine, on the behavioral (forced swimming test [FST], sucrose preference [SPT] and prepulse inhibition [PPI] of the startle) and neurochemical (glutathione [GSH], lipid peroxidation, IL-1β) alterations in the prefrontal cortex, hippocampus and striatum as well as in BDNF levels in the hippocampus 24h after LPS (0.5mg/kg, i.p.) administration, a time-point related to depressive-like behavior. ⋯ The pretreatment with the NOS inhibitors, l-NAME and aminoguanidine as well as sildenafil prevented the behavioral and neurochemical alterations induced by LPS, although sildenafil and l-NAME were not able to prevent the increase in hippocampal BDNF levels induced by LPS. The iNOS inhibitor, aminoguanidine, and imipramine prevented all behavioral and neurochemical alterations induced by LPS. l-arginine did not prevent the alterations in immobility time, sucrose preference and GSH induced by LPS. Taken together our results show that the NO-cGMP pathway is important in the modulation of the depressive-like alterations induced by LPS.