Neuroscience
-
The present study is the first to explore the multigenerational effects of mammalian paternal cocaine intake on offspring (F1) circadian clock regulation. Parental cocaine use poses significant health risks to the offspring, through both maternal and paternal drug influences. With respect to the latter, recent evidence suggests that a paternal mode of cocaine inheritance involves epigenetic germ line actions that can ultimately disrupt offspring behavior. ⋯ In contrast, F1 cocaine-sired females, but not males, had suppressed circadian phase advance shifting responses to two non-photic stimuli: acute i.p. injections of cocaine and the serotonin agonist ([+]8-OH-DPAT). The reduced cocaine shifting in females was not due to suppressed cocaine-induced behavioral arousal. Collectively, these results reveal that a father's cocaine use can disrupt major circadian entrainment mechanisms in his adult progeny in a sex-dependent manner.
-
Comparative Study
Sex Differences and Estrous Cycle Changes in Synaptic Plasticity-related microRNA in the Rat Medial Amygdala.
The posterodorsal medial amygdala (MePD) is a sex steroid-sensitive and sexually dimorphic subcortical area that dynamically modulates social behaviors in rats. As different microRNA (miRNA) can act as post-transcriptional regulators of synaptic processing, we addressed changes that occur in miRNA expression in the MePD of males and females along the estrous cycle. The expression of miR25-3p, miR132-3p, miR138-5p, miR181a-5p, miR195-5p, and miR199a-5p, involved in neuronal cytoskeleton remodeling and synaptic plasticity, were evaluated by RT-qPCR. ⋯ In addition, diestrus females showed higher values of miR25-3p, miR181a-5p, and miR195-5p when compared to estrus females. These miRNA expression profiles indicate a variable and fine-tuned protein regulation in the adult MePD. It is likely that these miRNA can be involved in structural and functional synaptic features and plasticity characteristic of males and cycling females and for the MePD regulation of mammalian reproduction.
-
Dendritic spines have stable filamentous actin (F-actin) and dynamic F-actin. The formation of stable F-actin plays a pivotal role in spine formation. Drebrin binds to and stabilizes F-actin in dendritic spines. ⋯ In addition, F-actin depolymerization with latrunculin A significantly reduced the stable GFP-DA fraction. These findings indicate that preferential binding of drebrin A to F-actin than drebrin E causes higher stable fraction of drebrin A in dendritic spines, although the F-actin-binding ability of purified drebrin E and drebrin A are comparable. Therefore, we suggest that a drebrin isoform conversion from drebrin E to drebrin A in dendritic spines results in the accumulation of drebrin-bound stable F-actin, which plays a pivotal role in synapse formation.
-
Phosphorylation of α-synuclein at serine 129 (P-Ser 129 α-syn) is involved in the pathogenesis of Parkinson's disease (PD) and Lewy body (LB) formation. However, there is no clear evidence indicates the quantitative relation of P-Ser 129 α-syn accumulation and dopaminergic cell loss, LBs pathology and the affected brain areas in PD monkeys. Here, pathological changes in the substantia nigra (SN) and PD-related brain areas were measured in aged monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) utilizing a modeling-recovery-remodeling strategy. ⋯ P-Ser 129 α-syn aggregations or LB-like pathology was also found in the midbrain and the neocortex, specifically in the oculomotor nucleus (CN III), temporal cortex (TC), prefrontal cortex (PFC) and in cells surrounding the third ventricle. Notably, the occipital cortex (OC) was P-Ser 129 α-syn negative. The findings of LB-like pathologies, dopaminergic cell loss and the stability of the PD symptoms in this model suggest that the modeling-recovery-remodeling strategy in aged monkeys may provide a new platform for biomedical investigations into the pathogenesis of PD and potential therapeutic development.
-
The mitotic activity of certain tissues in the body is closely associated with circadian clock function. However, the effects of growth factors on the molecular clockwork are not fully understood. Stimulation of neural stem cells (NSCs) with epidermal growth factor (EGF), a well-known mitogen, is known to cause synchronized cell cycle progression with a period of approximately 24 h, closely associated with the Per2 gene expression rhythm. ⋯ EGF led to gene induction in the presence of cycloheximide, suggesting that de novo protein synthesis is unnecessary. Pretreatment with the MEK1/2 inhibitor U0126 significantly suppressed the acute induction of Per2, Dec1, and Noct by EGF and also abolished the EGF-induced phase shift of the PER2::LUCIFERASE rhythm in NSCs. These results suggest a unique effect of EGF on the molecular clockwork of NSCs.