Dissociating neural correlates of retrieval practice and elaborative study in associative recognition memory Retrieval practice effect refers to better long-term retention enhanced by active retrieval compared to re-studying, which has been widely demonstrated. However, controversies remain as to whether the underlying mechanism of this effect could be attributed to semantic elaboration. We investigated whether retrieval practice and elaboration were equivalent by observing the underlying cognitive processes of the two conditions using corresponding event-related potentials measures of associative memory and item memory. Behavioral results showed that retrieval practice induced better associate memory performance than elaborative study. For event-related potential results, an early old/recombined effect (FN400) related to familiarity and a late old/recombined effect (late positive component) related to recollection emerged in the retrieval practice condition, while both were absent in the elaborative study condition. An early recombined/new effect (FN400) appeared in the elaborative study condition, which did not occur in the retrieval practice condition. It could be inferred that retrieval practice promoted the recollection of episodic contexts for later associative memory, while elaborative study strengthened the familiarity of individual item. These findings suggest that retrieval practice and elaboration are two distinctive processes.

Protective effects of 3,4-dihydroxyphenylethanol on spinal cord injury-induced oxidative stress and inflammation 3,4-Dihydroxyphenylethanol (DOPET) is a potent antioxidant polyphenolic compound. In this study, our objective was to investigate the underlying mechanism of the neuroprotective role of DOPET in attenuating spinal cord injury (SCI). Initially, SCI was induced by performing surgical laminectomy on the rats at T10-T12 level. Then, the neurological function-dependent locomotion was measured using Basso Beattie Bresnahan score, which declined in the SCI-induced group. Increased antioxidant levels such as superoxide dismutase, glutathione peroxidase, and glutathione along with other parameters such as increased lipid peroxidation (LPO) and myeloperoxidase (MPO) activities were all observed in the SCI group. Levels of proinflammatory cytokines such as tumor necrosis factor-α and interleukin-1β were upregulated in the serum and spinal cord tissue as observed on the immunoblot. Interestingly, protein levels of apoptotic markers such as Bax, cleaved caspase 3 and RT-PCR analysis-based mRNA level of pro-inflammatory cytokine, nuclear factor- κ activated B cells (NF-κB) were significantly upregulated in the spinal cord tissue. Nonetheless, antiapoptotic factor such as B-cell lymphoma 2 (Bcl-2) protein expression was downregulated in the same group. However, on administering 10 mg/kg of DOPET, the neuronal function was rescued, antioxidants were restored back to the normal levels, LPO and MPO activities were reduced in conjunction with downregulated levels of proinflammatory cytokines and apoptotic markers in the SCI group. These findings show that DOPET could potentially target multiple signalling pathways to combat SCI.

Drosophila Alpha-ketoglutarate-dependent dioxygenase AlkB is involved in repair from neuronal disorders induced by ultraviolet damage AlkB family proteins are enzymes that repair alkylated DNA and RNA by oxidative demethylation. Nine homologs have been identified and characterized in mammals. ALKBH1 is conserved among metazoans including Drosophila. Although the ALKBH1 mouse homolog, Alkbh1 functions in neurogenesis, it currently remains unclear whether ALKBH1 plays a role in neuronal disorders induced by ultraviolet-induced DNA damage. We herein demonstrated that the Drosophila ALKBH1 homolog, AlkB contributed to recovery from neuronal disorders induced by ultraviolet damage. The knockdown of AlkB resulted in not only learning defects but also altered crawling behavior in Drosophila larvae after ultraviolet irradiation. A molecular analysis revealed that AlkB contributed to the repair of ultraviolet-induced DNA damage in the central nervous system of larvae. Therefore, we propose that ALKBH1 plays a role in the repair of ultraviolet-induced DNA damage in central nervous system. Ultraviolet-induced DNA damage is involved in the pathogenesis of xeroderma pigmentosum, and has recently been implicated in Parkinson’s disease. The present results will contribute to our understanding of neuronal diseases induced by ultraviolet-induced DNA damage.

Differential distributions of parvalbumin-positive interneurons in the sulci and gyri of the adult ferret cerebral cortex Although accumulating evidence suggests that there are significant anatomical and histological differences between the sulci and gyri of the cerebral cortex, whether there is a difference in the distribution of interneurons between the two cortical regions remains largely unknown. In this study, we systematically compared the distributions of parvalbumin-positive interneurons among three neighboring gyrus and sulcus pairs—coronal gyrus and cruciate sulcus, anterior ectosylvian gyrus and rostral suprasylvian sulcus, and posterior ectosylvian gyrus and pseudosylvian sulcus—in the adult ferret cerebral cortex. We proposed a method to partition sulci and gyri into several specific subregions through the deepest points of the sulci and the highest points of gyri in the inner and outer cortical contours of coronal sections. We found that the density of parvalbumin-positive interneurons in the gyri was significantly higher than that in the sulci. Further study revealed that the density of PV+ interneurons in superficial cortical layers (layers 2/3 and layer 4) was comparable among the three pairs of sulci and gyri. However, the density of parvalbumin-positive interneurons in cortical layers 5/6 was significantly higher in gyri than in sulci. These results indicate that parvalbumin-positive interneurons are differently distributed in infragranular layers of cortical sulci and gyri.

Incorporation of one N-glycosylation-deficient subunit within a tetramer of HCN2 channel is tolerated Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are glycoproteins N-glycosylated at a specific asparagine residue in the S5-S6 linker region. Previous reports suggested that N-glycosylation-deficient HCN2 N380Q (NQ) channels fail to properly target to the plasma membrane and are unable to form functional ion channels. HCN channels are known to homo- and hetero-oligomerize and it is not known whether HCN2-NQ subunits can oligomerize with wild type (wt) N-glycosylated subunits to form a tetrameric assembly. In the present study, homomeric NQ-mutant resulted in no current, cRNA titration experiments controlling the amount of wt-to-NQ injected into Xenopus oocytes indicated that the observed currents were consistent with a model where presence of a single nonglycosylated subunit in a tetrameric oligomer is tolerated forming functional channels. The activation voltage-dependence described by half-activation voltage and slope factor, and the reversal potential of the wt-NQ oligomeric channels were identical to the wt only tetrameric channels. Further incorporation of the nonglycosylated subunit rendered the channels nonconductive or not incorporated into the plasma membrane.

Effect of trace amine-associated receptor 1 agonist RO5263397 on sensory gating in mice The trace amine-associated receptor 1 (TAAR1) agonist RO5263397 effect on sensory gating in C57BL/6 mice was studied. Sensory gating is a mechanism for dosing and filtering the incoming information, by which the brain regulates the responses to sensory stimuli coming from the environment. Sensory gating deficit is considered to be one of the schizophrenia endophenotypes. TAAR1 agonist at a 1 mg/kg dosage contributed to the sensory gating index (S1–S2) increase. Sensory gating index rose due to the N40 amplitude increase in response to the first stimulus in a pair, whereas the amplitude of the second stimulus remained unchanged. These results suggest that the sensory gating in mice may be modulated through TAAR1-dependent processes, indicating potential contribution of TAAR1 and trace amines in general to the neuropharmacology of cognitive processes.

Dendritic cell factor 1 deletion leads to developmental defects in mushroom-shaped dendritic spines Dendritic spines are divided into four subtypes, namely, Mushroom, Stubby, Thin, and Branched. The mushroom-shaped spines are related to learning and memory. Previous studies have shown that the dendritic cell factor 1 (Dcf1, a transmembrane protein) affects the memory process and regulates the development of dendritic spines by inhibiting the expression of lipocalin 2 (Lcn2, a member of the family containing over 20 small secreted proteins). However, the exact subtype of dendritic spines that are specifically affected by Dcf1 remains unknown. Here, we identified that deletion of Dcf1 leads to developmental defects in mushroom-shaped spines. We provide evidence for memory defects caused by Dcf1-knockout in mice. We discovered and report for the first time that Dcf1 affects the development of mushroom-shaped spines by inhibiting the expression of Lcn2. Further, we demonstrated that environmental enrichment can effectively stimulate Dcf1-knockout mice and rescue development defects in mushroom-shaped spines caused by Dcf1 deletion. Our results provide a novel direction for further studies on dendritic spine development and mechanisms associated with learning and memory.

RE-1 silencing transcription factor alleviates the growth-suppressive effects of propofol on mouse neuronal cells Objective: Propofol is broadly utilized for maintaining anesthesia. Propofol affects neurodegeneration and neurogenesis by regulation of autophagy via effects on intracellular calcium homeostasis. The underlying molecular mechanism, however, is still unclear. Methods: In the present research, we systematically analyzed the effect of propofol on mouse neuronal cells (cell line: HT-22). Cell Counting Kit-8 assays were utilized to examine cell proliferation. Flow cytometry was used to determine the levels of cell apoptosis. Quantitative real-time PCR and western blot were used to examine the relative mRNA and protein levels in mouse neuronal cells. Results: Our results suggest that propofol inhibits proliferation and promotes apoptosis in neuronal cells. Moreover, overexpression of the transcriptional repressor RE-1 silencing transcription factor rescued the effect of propofol on neuronal cells. Additionally, the autophagy inhibitor 3-methyladenine also significantly reduced the effect of propofol on mouse neuronal cells. Finally, overexpression of RE-1 silencing transcription factor promoted the expression of brain-derived neurotrophic factor in mouse neuronal cells. Conclusion: Our research not only enhances our understanding of propofol on mouse neuronal cells but also uncovers a potential signaling pathway that may mediate the effects of propofol on neuronal cells.

Overexpression of immunoproteasome low-molecular-mass polypeptide 7 and inhibiting role of next-generation proteasome inhibitor ONX 0912 on cell growth in glioma Objectives: The aim of this study was to determine the expression level of immunoproteasome and its clinical significance in glioma preliminarily. Furthermore, we studied the function and molecular mechanism of proteasome inhibitor ONX 0912 on glioma cell. Materials and methods: The expression of immunoproteasome in glioma and tumor-adjacent brain tissues was detected by western blot. Immunohistochemical technique was used to detect the expression of low-molecular-mass polypeptide 7 in 55 cases of glioma tissues and 6 cases of tumor-adjacent brain tissues. Chi-square test was used to analyze the relationship between the expression level of low-molecular-mass polypeptide 7 and clinical characteristics. Kaplan–Meier method and Cox regression analysis were applied to analyze the correlation between low-molecular-mass polypeptide 7 expression and prognosis of patients. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium) (MTS) proliferation assay was introduced to detect the impact of ONX 0912 on proliferation of glioma cells. Western blot was used to detect the apoptosis- and autophagy-related protein in glioma cell treated with ONX 0912. Results: Our results showed that only low-molecular-mass polypeptide 7 expression was notably upregulated in gliomas in comparison with tumor-adjacent brain tissues and further increased in malignant gliomas compared with benign gliomas (P < 0.01). In the multivariate Cox proportional regression analyses, it was evident that low-molecular-mass polypeptide 7 was an independent unfavorable prognostic factor (P < 0.05). The results of MTS assay showed that ONX 0912 could inhibit the proliferation of glioma cell. Besides, we found that ONX 0912 could prompt apoptosis and autophagosome accumulation, which may be responsible for inhibiting glioma cell proliferation. Conclusion: In conclusion, our results indicated that low-molecular-mass polypeptide 7 might be a candidate prognostic biomarker, and proteasome inhibitor ONX 0912 might act as a potential treatment agent for glioma.

Gastrin-releasing peptide inhibits CA1 neurons via increasing inhibitory synaptic transmissions in hippocampal slices of rats Gastrin-releasing peptide plays an important role in regulating the advanced functions of the brain including emotional behavior, learning and memory. What’s more, gastrin-releasing peptide levels are also associated with the central nervous system diseases. Our previous study proposed that intraperitoneal injection of gastrin-releasing peptide can improve spatial memory in chronic ischemic model rats. It is well known that the hippocampus is an important brain area related to spatial learning and memory, but the mechanisms of gastrin-releasing peptide on hippocampal neurons are still unclear. In this study, we examined the effects of gastrin-releasing peptide on excitability of hippocampal CA1 neurons and further explored the mechanisms of its effects on synaptic transmission. The results showed that gastrin-releasing peptide inhibited the excitability of CA1 neurons and increased the amplitude and frequency of inhibitory postsynaptic currents significantly. In summary, we demonstrate that gastrin-releasing peptide can inhibit the excitability of hippocampal CA1 area neurons in brain slices and clarify the synaptic transmission mechanism involved in this process, which provide a theoretical basis for gastrin-releasing peptide to improve animal cognitive function, and new ideas for the treatment of related central nervous system diseases.