Neuroscience
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Eating palatable foods can provide stress relief, but the mechanisms by which this occurs are unclear. We previously characterized a limited sucrose intake (LSI) paradigm in which twice-daily access to a small amount of 30% sucrose (vs. water as a control) reduces hypothalamic-pituitary-adrenocortical (HPA) axis responses to stress and alters neuronal activation in stress-regulatory brain regions in male rats. However, women may be more prone to 'comfort feeding' behaviors than men, and stress-related eating may vary across the menstrual cycle. ⋯ Finally, Bayesian network modeling of the FosB/deltaFosB and pCREB expression data identified a neurocircuit that includes the BLA, nucleus accumbens, prefrontal cortex, and bed nucleus of the stria terminalis as likely being modified by LSI during P/E. When considered in the context of our prior results, the present findings suggest that palatable food reduces stress responses in female rats similar to males, but in an estrous cycle-dependent manner. Further, the BLA may contribute to the LSI effects in both sexes, whereas the involvement of other brain regions appears to be sex-dependent.
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A-kinase-anchoring proteins, AKAPs, are scaffolding proteins that associate with kinases and phosphatases, and direct them to a specific submembrane site to coordinate signaling events. AKAP150, a rodent ortholog of human AKAP79, has been extensively studied in neurons, but very little is known about the localization and function of AKAP150 in astrocytes, the major cell type in brain. Thus, in this study, we assessed the localization of AKAP150 in astrocytes and elucidated its role during physiological and ischemic conditions. ⋯ Knock-down of AKAP150 by RNAi depolarizes the astrocytic membrane potential and substantially reduces by 80% the ability of astrocytes to take up extracellular potassium during ischemic conditions. Therefore, upregulation of AKAP150 during ischemia preserves potassium conductance and the associated hyperpolarized membrane potential of astrocytes; properties of astrocytes needed to maintain extracellular brain homeostasis. Taken together, these data suggest that AKAP150 may play a pivotal role in the neuroprotective mechanism of astrocytes during pathological conditions.
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Experience-dependent synaptic plasticity is an important component of both learning and motivational disturbances found in addicted individuals. Here, we investigated the role of cocaine experience-dependent plasticity at excitatory synapses in the nucleus accumbens shell (NAcSh) in relapse-related behavior in mice with a history of volitional cocaine self-administration. ⋯ Furthermore, we show that these effects are due to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-specific mechanisms that differ depending on the nature and context of the reinstatement-inducing stimuli. Together, our findings identify common themes as well as differential mechanisms that are likely important for the ability of diverse environmental stimuli to drive relapse to addictive-like cocaine-seeking behavior.
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A disintegrin and metalloprotease protein 23 (ADAM23) is a transmembrane type I glycoprotein involved with the development and maintenance of the nervous system, including neurite outgrowth, neuronal adhesion and differentiation and regulation of synaptic transmission. In addition, ADAM23 seems to participate in immune response and tumor establishment through interaction with different members of integrin receptors. Here, we describe a novel monoclonal antibody (DL11C8) that specifically recognizes the cysteine-rich domain of both pre-protein (100 kDa) and mature (70 kDa) forms of ADAM23 from different species, including human, rodents and avian orthologs. ⋯ Indeed, the mature ADAM2370 kDa partitions between raft and non-raft membrane domains, while the pro-protein ADAM23100 kDa is mainly expressed in non-raft domains. These membranous distributions were observed in both different brain regions homogenates and primary cultured neurons lysates from mouse cortex and cerebellum. Taken together, these findings point out ADAM23 as a lipid raft molecular component.
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Several conditions related to the intrauterine environment are associated with neuropsychiatric conditions in later life. In humans, approximately 2% of infants are exposed to perinatal hypoxia-ischemia or prolonged anoxic insult, a condition to which very low birth weight preterm infants exhibit the highest susceptibility. Analyses of postmortem tissue link some presentations of these conditions to changes in GABA pathway functionality in the brains of affected subjects. ⋯ Finally, changes in guidance molecules in the developing cortex, including increases in hypoxia-inducible factor 1-alpha levels and intracellular distribution, decreases in reelin levels in the cortical plate and altered organization of radial glia, were observed. These changes in the molecular landscape of the immediate environment of the immature neurons may contribute to the observed outcomes in neuronal migration to, and establishment in, the correct cortical layers. We suggest that the interneuron loss may be related to these early events.