Neuroscience
-
Abelson interactor protein 1 (Abi-1) localizes to postsynaptic densities (PSDs) of excitatory synapses and was shown to be transported from the PSD to the nucleus and back depending upon synaptic activation. We employed a yeast-two-hybrid screen to search for putative transport molecules. We found Kif26B a member of the Kif family of transport proteins that has not been characterized in the central nervous system as a direct interaction partner of Abi-1. ⋯ Kif26B was able to recruit Abi-1 to the microtubule network and we found that the expression of Kif26B is responsible for the localization of Abi-1 to PSDs in maturing neurons. Taken together we report that Abi-1 is a cargo of Kif26B in primary hippocampal neurons, pointing to a role of this transport molecule in the movement of Abi-1 between different cell compartments. Additionally, we provide the first detailed investigation of Kif26B and its cargo molecules in neuronal cells.
-
Cortical surface area has been largely overlooked in genetic studies of human brain morphometry, even though phylogenetic differences in cortical surface area between individuals are known to be influenced by differences in genetic endowment. In this study, we examined the relative contribution of genetic and environmental influences on cortical surface areas in both the native and stereotaxic spaces for a cohort of homogeneously-aged healthy pediatric twins. ⋯ This is reasonable since whole brain volume is also known to be heritable itself and so removing that component of areal variance due to overall brain size via stereotaxic transformation will reduce the genetic proportion. These findings further suggest that cortical surface areas involved in cognitive, attention and emotional processing, as well as in creating and retaining of long-term memories are likely to be more useful for examining the relationship between genotype and behavioral phenotypes.
-
Experimental evidence in mice indicates that environmental conditions affect females and males differently. However, in a recent study analyzing the heterozygous mutation of brain-derived neurotrophic factor (BDNF), both sexes presented a similar emotional phenotype, which became obvious only under impoverished, but not in enriched conditions suggesting an "enrichment-induced" rescue. To investigate the basis of this behavioral "rescue" effect, we analyzed neurochemical changes (BDNF expression, serotonergic changes, and corticosterone) in the hippocampus, frontal cortex and hypothalamus of animals housed under respective conditions. ⋯ Male and female corticosterone levels were neither affected by "genotype" nor by "environment". In conclusion, we propose that the rescue of the emotional phenotype by environmental enrichment in BDNF(+/-) mice is directed by distinct mechanisms in males and females. Only in male BDNF(+/-) mice the rescue is related to an increase in hippocampal BDNF expression suggesting that enrichment triggers different neuronal systems in a gender-specific manner.
-
Antagonism of the kappa opioid receptor (KOR) has been reported to have anti-depressant-like properties. The dynorphin/KOR system is a crucial neurochemical substrate underlying the pathologies of addictive diseases, affective disorders and other disease states. However, the molecular underpinnings and neuroanatomical localization of the dysregulation of this system have not yet been fully elucidated. ⋯ The corresponding brain regions from the opposite hemisphere were analyzed for underlying chromatin modifications of the prodynorphin gene promoter region using chromatin immunoprecipitation with antibodies against specifically methylated histones H3K27Me2, H3K27Me3, H3K4Me2, and H3K4Me3, as well as CREB-1 and MeCP2. Significant alterations in proteins bound to DNA in the Cre-3, Cre-4, and Sp1 regions of the prodynorphin promoter were found in the caudate putamen of the FST saline-treated animals compared to control animals, with no changes observed in the hippocampus. Epigenetic changes resulting in elevated dynorphin levels specifically in the caudate putamen may in part underlie the enduring effects of stress.
-
Ginsenoside Rg1, which could improve spatial learning and memory, might be a useful agent for preventing and treating cognitive impairment in Alzheimer's disease (AD). The present study was designed to test the neuroprotective effects of ginsenoside Rg1 on an ovariectomized (OVX) and d-galactose (d-gal)-injected rat model of AD, which is characterized with progressive learning and memory deficits, AD-related molecules alteration and differentiation/apoptosis imbalance in hippocampal neurons. OVX Wistar rats received daily injections of d-gal (100mg/kg) combined with different concentrations of ginsenoside Rg1 (5, 10, 20mg/kg) or 17-β-estradiol (E2, 100 μg/kg), or normal saline (NS, 1.0 ml/kg) for 6 weeks. ⋯ Ginsenoside Rg1 and E2-treatment increased ADAM 10 level while reduced BACE 1 level and apoptosis. Moreover, moderate i.e. 10mg/kg/d and high i.e. 20mg/kg/d ginsenoside Rg1 displayed more effective function than low i.e. 5mg/kg/d ginsenoside Rg1. Our findings demonstrate the neuroprotective effects of ginsenoside Rg1 and E2 on AD rats and support the potential application of ginsenoside Rg1 in the treatment of learning and memory impairments in postmenopausal women.