Neuroscience
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Epidemiological and clinical studies provide growing evidence for marked sex differences in the incidence of certain neurological disorders that are largely attributed to the neuroprotective effects of estrogen. Thus there is a keen interest in the clinical potential of estrogen-related compounds to act as novel therapeutic agents in conditions of neuronal injury and neurodegeneration such as Parkinson's disease. Studies employing animal models of neurodegeneration in ovariectomised female rats treated with estrogen support this hypothesis, yet experimental evidence for sex differences in the CNS response to direct neurotoxic insult is limited and, as yet, few studies have addressed the role played by endogenously produced hormones in neuroprotection. ⋯ Taken together, our findings strongly suggest that there are sex differences in the mechanisms whereby nigrostriatal dopaminergic neurones respond to injury. They also reveal that the reported clinically beneficial effects of estrogen in females may not be universally adopted for males. While the reasons for this gender-determined difference in response to the activational action of estrogen are unknown, we hypothesize that they may well be related to the early organizational events mediated by sex steroid hormones, which ultimately result in the sexual differentiation of the brain.
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S-allyl-L-cysteine (SAC), one of the organosulfur compounds found in aged garlic extract, has been shown to possess various biological effects including neurotrophic activity. In our previous experiments, we found that SAC could protect against amyloid beta-protein (Abeta)- and tunicamycin-induced cell death in differentiated PC12 cells. In the study described here, we characterized the neuronal death induced by Abeta, 4-hydroxynonenal (HNE), tunicamycin, and trophic factor deprivation, and investigated whether and how SAC could prevent this in cultured rat hippocampal neurons. ⋯ SAC also attenuated the Abeta-induced increase of intracellular reactive oxygen species in hippocampal neurons. SAC had no effect on Abeta-induced cell death in cultured cerebellar granule neurons, which was prevented by a caspase-3 inhibitor. These results suggest that SAC could protect against the neuronal cell death that is triggered by ER dysfunction in the hippocampus, and that it has no effect on neuronal cell death that is dependent upon the caspase-3 mediated pathway.
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In order to investigate neural mechanisms by which the prefrontal cortex adaptively modifies its activities based on past experience, we examined whether or not sensory cortical projections to the medial prefrontal cortex support long-term potentiation (LTP) in rats. Monosynaptic projections from the secondary visual cortex, mediomedial area (V2MM) to the infralimbic cortex were confirmed by orthodromic as well as antidromic activation of single units. ⋯ LTP was also induced in the ventral hippocampal projection to the infralimbic cortex by the same high-frequency stimulation. The present results suggest that modification of synaptic weights of afferent sensory cortical projections is one mechanism underlying learning-induced changes in prefrontal cortical neural activities.
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The distribution of N-methyl-D-aspartate- (NMDA) and kainic acid- (KA) sensitive ionotropic glutamate receptors (iGluR) in the zebrafish olfactory bulb was assessed using an activity-dependent labeling method. Olfactory bulbs were incubated with an ion channel permeant probe, agmatine (AGB), and iGluR agonists in vitro, and the labeled neurons containing AGB were visualized immunocytochemically. Preparations exposed to 250 microM KA in the presence of a NMDA receptor antagonist (D-2-amino-5-phosphono-valeric acid) and an alpha-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist (sym 2206), revealed KA receptor-mediated labeling of approximately 60-70% of mitral cells, juxtaglomerular cells, tyrosine hydroxylase-positive cells and granule cells. ⋯ Application of 333 microM NMDA in the presence of an AMPA/KA receptor antagonist (6-cyano-7-nitroquinoxaline-2,3-dione) resulted in NMDA receptor-mediated labeling of almost all neurons. The concentrations eliciting 50% of the maximal response (effective concentration: EC(50)s) for NMDA-stimulated labeling of different cell types were not significantly different and ranged from 148 microM to 162 microM. These results suggest that while NMDA receptors with similar binding affinities are widely distributed in the neurons of the zebrafish olfactory bulb, KA receptors are heterogeneously expressed among these cells and may serve unique roles in different regions of the olfactory bulb.
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Comparative Study
Focal motility determines the geometry of dendritic spines.
The geometry of dendritic spines has a major impact on signal transmission at excitatory synapses. To study it in detail we raised transgenic mice expressing an intrinsic green fluorescent protein-based plasma membrane marker that directly visualizes the cell surface of living neurons throughout the brain. ⋯ In live mature dendrites up to 50% of spines had cup-shaped heads with prominent terminal lamellipodia whose motility produced constant alterations in the detailed geometry of the synaptic contact zone. The partial enveloping of presynaptic terminals by these cup-shaped spines coupled with rapid actin-driven changes in their shape may operate to fine-tune receptor distribution and neurotransmitter cross-talk at excitatory synapses.