Neuroscience
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Early life experiences, particularly the experience with parents, are crucial to phenotypic outcomes in both humans and animals. Although the effects of maternal deprivation on offspring well-being have been studied, paternal deprivation (PD) has received little attention despite documented associations between father absence and children health problems in humans. In the present study, we utilized the socially monogamous prairie vole (Microtus ochrogaster), which displays male-female pair bonding and bi-parental care, to examine the effects of PD on adult behaviors and neurochemical expression in the hippocampus. ⋯ Further, PD experience increased glucocorticoid receptor beta (GRβ) protein expression in the hippocampus of females as well as increased corticotrophin receptor 2 (CRHR2) protein expression in the hippocampus of males, but decreased CRHR2 mRNA in both sexes. Together, our data suggest that PD has a long-lasting, behavior-specific effect on SOA and alters hippocampal neurochemical systems in the vole brain. The functional role of such altered neurochemical systems in social behaviors and the potential involvement of epigenetic events should be further studied.
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The intergeniculate leaflet (IGL) is a flat thalamic nucleus implicated in the modulation of circadian rhythmicity. In rat, two main GABAergic subpopulations can be distinguished in the IGL: neurons synthesizing neuropeptide Y (NPY), which directly innervates the suprachiasmatic nuclei, and enkephalinergic cells, which connect contralaterally located leaflets. The aim of this study was to evaluate possible effects of inner IGL neurotransmitters on the spontaneous and synaptic activity of IGL neurons. ⋯ Moreover, we investigated the type of opioid receptor activated by enkephalin and showed that the μ-receptor is functionally predominant in the IGL. The application of met-enkephalin not only robustly hyperpolarized IGL neurons (both putatively NPY-synthesizing and putatively enkephalinergic neurons), but it also was able to inhibit GABAergic and glutamatergic synaptic transmission. Based on this and previous studies, we hypothesize that IGL enkephalinergic neurons may act as powerful interneurons that inhibit themselves and NPY-synthesizing neurons, also in the contralaterally located IGL.
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The aim of the present study was to determine whether adeno-associated viral vector (AAV) mediated transfer of ciliary neurotrophic factor (CNTF) and RhoA shRNA has additive effects on promoting the survival and axon regeneration of retinal ganglion cells (RGCs) after optic nerve crush (ONC). Silencing effects of AAV-RhoA shRNA were confirmed by examining neurite outgrowth in PC12 cells, and by quantifying RhoA expression levels with western blotting. Young adult Fischer rats received an intravitreal injection of (i) saline, (ii) AAV green fluorescent protein (GFP), (iii) AAV-CNTF, (iv) AAV-RhoA shRNA, or (v) a combination of both AAV-CNTF and AAV-RhoA shRNA. ⋯ In the ONC model, AAV-RhoA shRNA by itself had only weak beneficial effects on RGC axon regeneration. However, when combined with AAV-CNTF, AAV-RhoA shRNA significantly improved the therapeutic effect of AAV-CNTF on axon regeneration by nearly two fold, even though there was no significant change in RGC viability. In sum, this combination of vectors increases the regenerative response and can lead to more successful therapeutic outcomes following neurotrauma.
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Comparative Study
Direct comparison of microglial dynamics and inflammatory profile in photothrombotic and arterial occlusion evoked stroke.
Many focal cerebral ischemia models utilize the middle cerebral artery occlusion (MCAO) evoked by coagulation to induce ischemic damage in the cortex and mimic the pathology observed in human patients. A second, increasingly popular model, the photothrombotic stroke, uses a laser beam to irradiate the MCA after administration of a photosensitizing dye. This widely used procedure is slowly replacing the MCAO model because of the easiness of the surgical protocol and the reproducibility of the damage. ⋯ It also elicited higher levels of inflammatory cytokines/chemokines and increased infiltration from the periphery. In addition, only the neurons in the MCAO stroke showed phenotype plasticity by downregulating the transcription factor NeuN. These data provide a better understanding of the exact temporal and spatial dynamics of the inflammatory response in these two animal models of stroke and identify more relevant targets for human therapy.
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In the spinal cord high extracellular glutamate evokes excitotoxic damage with neuronal loss and severe locomotor impairment. During the cell dysfunction process, extracellular pH becomes acid and may activate acid-sensing ion channels (ASICs) which could be important contributors to neurodegenerative pathologies. Our previous studies have shown that transient application of the glutamate analog kainate (KA) evokes delayed excitotoxic death of spinal neurons, while white matter is mainly spared. ⋯ Likewise, immunohistochemistry indicated significant neuronal loss when KA was followed by the ASIC inhibitors DAPI or amiloride. Electrophysiological recording from ventral roots of isolated spinal cords showed that alternating oscillatory cycles were slowed down by 0.01mMKA, and intensely inhibited by subsequently applied DAPI or amiloride. Our data suggest that early rise in ASIC expression and function counteracted deleterious effects on spinal networks by raising the excitotoxicity threshold, a result with potential implications for improving neuroprotection.