Neuroscience
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Past research indicates that female meadow voles (Microtus pennsylvanicus) show decreased neurogenesis within the hippocampus during the breeding season relative to the non-breeding season, whereas male voles show no such seasonal changes. We expanded upon these results by quantifying a variety of endogenous cell proliferation and neurogenesis markers in wild-caught voles. Adult male and female voles were captured in the summer (breeding season) or fall (non-breeding season), and blood samples and brain tissue were collected. ⋯ Only the pHisH3 marker showed a sex difference, with females having a greater density of this cell proliferation marker than males. During the breeding season relative to the non-breeding season, males and females showed the predicted significant increases in testosterone and estradiol, respectively. Overall, these results suggest higher levels of neuronal turn-over during the non-breeding season relative to the breeding season, possibly due to seasonal changes in sex steroids.
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Macrophage migration inhibitory factor (MIF) plays an important role in hearing function; however, the underlying mechanism remains indistinct. PVM/Ms from the stria vascularis of lateral wall of cochlea in young and aged mice were isolated, and the mRNA and protein expression levels were detected. MIF was knocked down or overexpresssed in vitro, and transfection was performed in vivo. ⋯ Moreover, MIF effectively altered the expression levels of CDK1, BRAF, p-ERK1/2, p-PI3K, and p-Akt. Furthermore, ERK inhibitor PD98059 or PI3K inhibitor LY294002 significantly reversed the effects of Si-MIF on PVM/Ms from young mice, whereas ERK activator EGF or PI3K activator IGF significantly reversed the effects of Ad-MIF on PVM/Ms from aged mice. Taken together, MIF mediates the viability and apoptosis of PVM/Ms, at least partially, through MAPK and/or PI3K/Akt pathway.
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Global cerebral ischemia and reperfusion injury (GCI/R) can lead to neuronal apoptosis and contributes to permanent neurological sequelae. However, the underlying mechanism is largely unknown. Therefore, the present study aimed to assess the effects of GCI/R on the tribbles homolog 3 (TRB3) and to explore the role of TRB3 in GCI/R. ⋯ These data implied that TRB3 participated in the GCI/R-induced neuronal apoptosis. Knocking down TRB3 attenuated endoplasmic reticulum stress, enhanced Akt phosphorylation, and protected neurons from apoptosis in response to GCI/R. These results demonstrated that the downregulation of TRB3 may be a promising approach for treating GCI/R.
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Recently, alternative drug therapies for Parkinson's disease (PD) have been investigated as there are many shortcomings of traditional dopamine-based therapies including difficulties in treating cognitive and attentional dysfunction. A promising therapeutic avenue is to target mitochondrial dysfunction and oxidative stress in PD. One option might be the use of methylene blue (MB), an antioxidant and metabolic enhancer. ⋯ However, MB significantly improved attentional performance in the five-choice task designed to measure selective and sustained attention. In conclusion, MB might be useful in improving some attentional function and preserving dopaminergic cells in this model. Future work should continue to study and optimize the abilities of MB for the treatment of PD.
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Neuro-anatomical evidence supports the potential for threat-related factors, such as fear, anxiety and vigilance, to influence brainstem motor nuclei controlling eye movements, as well as the vestibular nuclei. However, little is known about how threat influences human ocular responses, such as eye saccades (ES), smooth pursuit eye tracking (SP), and optokinetic nystagmus (OKN), and whether these responses can be facilitated above normal baseline levels with a natural source of threat. This study was designed to examine the effects of height-induced postural threat on the gain of ES, SP and OKN responses in humans. ⋯ Significant correlations were found between changes in physiological arousal and OKN gain. Observations of changes with height in OKN and SP support neuro-anatomical evidence of threat-related mechanisms influencing both oculo-motor nuclei and vestibular reflex pathways. Although further study is warranted, the findings suggest that potential influences of fear, anxiety and arousal/alertness should be accounted for, or controlled, during clinical vestibular and oculo-motor testing.