Neuroscience
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The amygdala, prefrontal cortex, striatum and other connected forebrain areas are important for reward-associated learning and subsequent behaviors. How these structurally and functionally dissociable regions are recruited during initial learning, however, is unclear. Recently, we showed amygdalar nuclei were differentially recruited across different stages of cue-food associations in a Pavlovian conditioning paradigm. ⋯ Furthermore, within the perifornical lateral hypothalamus, tone-food pairings selectively recruited neurons that produce the orexigenic neuropeptide orexin/hypocretin. These data show a functional map of the forebrain areas recruited by appetitive associative learning and dependent on experience. These selectively activated regions include interconnected prefrontal, striatal, and hypothalamic regions that form a discrete but distributed network that is well placed to simultaneously inform cortical (cognitive) processing and behavioral (motivational) control during cue-food learning.
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Spinal cord injury (SCI) represents a severe health problem worldwide usually associated with severe disability and reduced quality of life. The aim of this work was to investigate the role of prohibitin 1 (PHB1) in the progression of SCI in rats. Firstly, we observed that expression of PHB1 was downregulated following SCI in rats. ⋯ Ad-PHB1 administration following SCI restored mitochondrial adenosine triphosphate formation, reduced reactive oxygen species formation, and improved mitochondrial respiration rates. Finally, Ad-PHB1 administration following SCI activated downstream signals including phosphatidylinositol-3-kinase (PI3K)/Akt, extracellular signal-regulated kinase (ERK1/2), and nuclear factor-kappaB. These data indicate that the PHB1 plays an important role in the development of SCI and might provide a therapeutic target to promote recovery from SCI.
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Fibroblast growth factor-2 (FGF-2) is a potent neurotrophic factor promoting survival of dopaminergic (DA) neurons in vitro and in vivo. FGF-2 is expressed in different isoforms representing distinct translation products from a single mRNA. For this study, we focused on the high molecular weight (HMW) isoform, which, after non-viral plasmid-based overexpression in embryonic day 12 (E12) rat ventral mesencephalon (VM)-derived cells, revealed increased numbers of tyrosine hydroxylase-positive (TH(+)) cells in a 'colayer' cell culture model. ⋯ Finally, the integration of the grafted cells into the host striatum was analyzed by immunohistochemical measurements. Those analyses revealed improvements of behavioral deficits in all five groups receiving DA neuron grafts, except for amphetamine-induced rotation of the FGF-2-HMW small graft group. Altogether, genetic modification with the FGF-2-HMW-plasmid did not further improve functional recovery compared to the control groups and had no influence on either the number of surviving DA neurons or on the density of outgrowing TH(+) fibers.
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In the dorsal facial area (DFA) of the medulla, an activation of either P2 purinergic receptor or nitric oxide synthase (NOS) results in the release of glutamate, leading to an increase in blood flow of the common carotid artery (CCA). It is not known whether activation of the P2 receptor by ATP may mediate activation of NOS/guanylyl cyclase to cause glutamate release and/or whether L-Arg (nitric oxide (NO) precursor) may also cause ATP release from any other neuron, to cause an increase in CCA flow. We demonstrated that microinjections of P2 receptor agonists (ATP, α,β-methylene ATP) or NO precursor (L-arginine) into the DFA increased CCA blood flow. ⋯ In conclusion, ATP activation of the P2 receptor in the DFA induced activation of neuronal NOS/guanylyl cyclase, which causes glutamate release leading to an increase in CCA blood flow. However, arginine activation of neuronal NOS/guanylyl cyclase, which also caused glutamate release and CCA blood flow increase, did not induce activation of P2 receptors. These findings provide important information for drug design and/or developing therapeutic strategies for the diseases associated with CCA blood flow that supplies intra- and extra-cranial tissues.
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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by a number of behavioral and social features. Although the etiology of most cases of ASD is idiopathic, a significant number of cases can be attributed to genetic causes, such as chromosome 15q duplications [dup(15q)]. Recent neuropathological investigations have provided evidence for distinct patterns of heterotopias and dysplasias in ASD and subjects with both ASD and dup(15q). ⋯ However, in subjects with dup(15q), we find significantly fewer neurons and in many nuclei, neurons were significantly smaller than in ASD subjects. Finally, we find a notably higher incidence of ectopic neurons in dup(15q). These results suggest that in the brainstem, these neuropathological conditions may evolve from some of the same developmental errors but are distinguished on microscopic features.