Neuroscience
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Pyrroloquinoline quinone (PQQ), a redox cofactor in the mitochondrial respiratory chain, has been shown to protect neurons against glutamate-induced damage both in vitro and in vivo. In this study, specific inhibitors to each of the mitochondrial complexes were used to find out which reactive oxygen species (ROS)-generating sites could be affected by PQQ. Then we established an in vitro model of Parkinson's disease (PD) by exposing cultured SH-SY5Y dopaminergic cells to rotenone, a complex I inhibitor. ⋯ Meanwhile, PQQ up-regulated the gene expression of Ndufs 1, 2, and 4 (complex I subunits), and increased mitochondrial viability and mitochondrial DNA content. Furthermore, PQQ pretreatment activated ERK1/2 phosphorylation in rotenone-injured SH-SY5Y cells, while ERK1/2 inhibition suppressed PQQ neuroprotection. All the results suggested that PQQ could protect SH-SY5Y cells against rotenone injury by reducing ROS production and maintaining mitochondrial functions through activation of ERK1/2 pathway.
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Major aspects of neuronal function are regulated by Ca(2+) including neurotransmitter release, excitability, developmental plasticity, and gene expression. We reported previously that sensory neurons isolated from a mouse model with a heterozygous mutation of the Nf1 gene (Nf1+/-) exhibited both greater excitability and evoked release of neuropeptides compared to wildtype mice. Furthermore, augmented voltage-dependent sodium currents but not potassium currents contribute to the enhanced excitability. ⋯ Quantitative real-time polymerase chain reaction measurements made from the isolated but intact dorsal root ganglia indicated that N-type (Cav2.2) and P/Q-type (Cav2.1) Ca(2+) channels exhibited the highest mRNA expression levels although there were no significant differences in the levels of mRNA expression between the genotypes. These results suggest that the augmented N-type (Cav2.2) ICa observed in the Nf1+/- sensory neurons does not result from genomic differences but may reflect post-translational or some other non-genomic modifications. Thus, our results demonstrate that sensory neurons from Nf1+/- mice, exhibit increased N-type ICa and likely account for the increased release of substance P and calcitonin gene-related peptide that occurs in Nf1+/- sensory neurons.
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Tyrosine-hydroxylase-positive (TH(+)) amacrine cells release dopamine in a paracrine manner and also form GABA-ergic contact sites with inner retinal neurons. The best known sites are formed by TH(+) fibrous rings and AII amacrine cell somata in stratum 1 of the inner plexiform layer (IPL). An AII amacrine cell is a highly compartmentalized neuron with relatively large soma, a stout dendritic stalk and two sets of processes, one showing lobular appearance and extending horizontally in stratum 1 and a second transversally elongated group of fibers in strata 4 and 5. ⋯ However, TH(+) fibers favored the soma/main stalk region of AII amacrine cells and only contacted lobular appendages and transversal processes sporadically. In addition to the well-studied contacts between AII cell somata and TH(+) rings in stratum 1 we found that the main stalk region in stratum 3 serves as a secondary major target for TH(+) axons. These data thus clearly show that TH(+) contacts to AII amacrine cells are highly compartment specific.
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Environmental enrichment can modulate mild and chronic stress, responses to anxiogenic stimuli as well as drug vulnerability in a number of animal models. The current study was designed to examine the impact of postnatal environmental enrichment on selectively bred 4th generation high- (HAn) and low-anxiety (LAn) male rats. After weaning, animals were placed in isolated (IE), social (SE) and enriched environments (EE) (e.g., toys, wheels, ropes, changed weekly). ⋯ In the physiological tests, animals housed in EE showed elevated adrenocortical responses to forced novel object exposure but decreased body temperature and blood pressure changes after an air puff stressor. All animals reared in EE and SE had elevated brain-derived neurotrophic factor (BDNF)-positive cells in the central amygdala (CeA), CA1 and CA2 hippocampal regions and the caudate putamen, but these differences were most pronounced in HAn rats for CeA, CA1 and CA2. Overall, these findings suggest that environmental enrichment offers benefits for trait anxiety rats including a reduction in behavioral and physiological responses to anxiogenic stimuli and AMPH sensitivity, and these responses correlate with changes in BDNF expression in the central amygdala, hippocampus and the caudate putamen.
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Rapid remodeling of neurons provides the brain with flexibility to adjust to environmental fluctuations. In Siberian hamsters, hippocampal dendritic morphology fluctuates across the day. To reveal the regulatory mechanism of diurnal remodeling of hippocampal neurons, we investigated the effects of light signals applied under different photoperiodic conditions on dendritic morphology. ⋯ Spine density of dentate gyrus (DG) dendrites was increased by a dark pulse in LD and spine density of CA1 basilar dendrites was decreased by a light pulse in SD. These results indicate that light signals induce rapid remodeling of dendritic morphology in a hippocampal subregion-specific manner. A light pulse in SD decreased hippocampal expression of fetal liver kinase 1 (Flk1), a receptor for vascular endothelial growth factor (VEGF), raising the possibility that VEGF-FLK1 signaling might be involved in the rapid decrease of branching or spine density of CA1 basilar dendrites by light.