Neuroscience
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Gait dysfunction, a hallmark of Parkinson's disease, contributes to a relatively high incidence of falling. Gait function is further diminished during the performance of a motor-cognitive task (i.e., dual-task). It is unclear if Parkinson's disease-related dual-task deficits are related to a specific area of cognitive function or are the result of a more global decline in executive function. ⋯ The attention and problem solving task resulted in the greatest number of gait parameter decrements. Results indicated that performance on cognitive tasks remained unchanged from single-task to dual-task conditions. Diminished gait performance under dual-task conditions across different cognitive function domains suggests a global Parkinson's disease-related deficit in information processing and regulation of gait.
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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.
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Activity-dependent transcription factors critically coordinate the gene expression program underlying memory formation. The tumor suppressor gene, MEN1, encodes a ubiquitously expressed transcription regulator required for synaptogenesis and synaptic plasticity in invertebrate and vertebrate central neurons. ⋯ In vivo knockdown of MEN1 prevented LTM formation and conditioning-induced changes in neuronal activity in the identified pacemaker neuron RPeD1. Our findings suggest the involvement of a new pathway in LTM consolidation that requires MEN1-mediated gene regulation.
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Cortices are non-uniform in their capacity for adaptive changes. In cat area 17, pinwheel centers of the orientation map demonstrated much greater selectivity shifts after the orientation adaptation than the iso-orientation domains (Dragoi et al., 2001a). However, whether this heterogeneity exists in other visual cortical regions remains unclear. ⋯ However, at either pinwheel centers or iso-orientation domains, the selectivity shifts in area 21a were all consistently greater than those in area 17, even though the heterogeneity in the orientation distribution was similar in the two areas. More importantly, in our short-term adaptation protocol, orientation adaptation in area 17 resulted in mostly repulsive shifts at the pinwheel center region, while in area 21a, it induced both repulsive and attractive effects. These results suggest that both common and distinct strategies exist for orientation adaptation across cortices and sub-regions.
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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.