Neuroscience
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The basolateral nuclear complex of the amygdala (BLC) receives dense noradrenergic/norepinephrine (NE) inputs from the locus coeruleus that play a key role in modulating emotional memory consolidation. Knowledge of the extent of synapse formation by NE inputs to the BLC, as well as the cell types innervated, would contribute to an understanding of how NE modulates the activity of the BLC. To gain a better understanding of NE circuits in the BLC, dual-label immunohistochemistry was used at the light and electron microscopic levels in the present study to analyze NE axons and their innervation of pyramidal cells in the anterior subdivision of the basolateral amygdalar nucleus (BLa). ⋯ The main postsynaptic targets were small-caliber CAMK+ dendritic shafts and spines of pyramidal cells. A smaller number of NET+ terminals formed synapses with unlabeled cell bodies and dendrites. These findings indicate that the distal dendritic domain of BLa pyramidal cells is the major target of NE terminals in the BLa, and the relatively low synaptic incidence suggests that diffusion from non-synaptic terminals may be important for noradrenergic modulation of the BLa.
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We have very little information about the metabolomic changes that mediate neurobehavioral responses, including addiction. It was possible that opioid-induced metabolomic changes in brain could mediate some of the pharmacodynamic effects of opioids. To investigate this, opiate-induced brain metabolomic responses were profiled using a semi-targeted method in C57BL/6 and 129Sv1 mice, which exhibit extreme differences in their tendency to become opiate dependent. ⋯ Morphine withdrawal behaviors were significantly diminished (p<0.0004) in genetically engineered mice with reduced adenosine tone in the brainstem, and by treatment with an adenosine receptor(1) (A(1)) agonist (2-chloro-N6-cyclopentyladenosine, 0.5mg/kg) or an A(2a) receptor (A(2a)) antagonist (SCH 58261, 1mg/kg). These results indicate that adenosine homeostasis plays a crucial role in narcotic drug responses. Opiate-induced changes in brain adenosine levels may explain many important neurobehavioral features associated with opiate addiction and withdrawal.
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Tissue and nerve damage can result in chronic pain. Yet, chronic pain after cesarean delivery is remarkably rare in women and hypersensitivity from peripheral nerve injury in rats resolves rapidly if the injury occurs in the puerperium. Little is known regarding the mechanisms of this protection except for a reliance on central nervous system oxytocin signaling. ⋯ The puerperium did not alter spinal cord microgial and astrocyte activation. Astrocyte activation, as measured by glial fibrillary acidic protein (GFAP) expression, was not evident in female rats with injury, regardless of delivery status suggesting sex differences in spinal astrocyte activation after injury. These results suggest a change in the descending inhibitory/facilitating balance on spinal nociception neurotransmission during the puerperium, as mechanisms for its protective effect against injury-induced hypersensitivity.
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The neuroprotective role of 17β-estradiol is well known; however, its mechanism of action remains unclear. In the present study, we applied light-induced apoptosis on the Sprague-Dawley rat retina to determine the neuroprotective effect of intravitreal administration of 17β-estradiol on retinal neurons and to demonstrate its underlying mechanism of action. Fourteen days after ovariectomy, adult female Sprague-Dawley rats received light damage. ⋯ This translocation was inhibited by pre-injection of LY294002. Taken together, these results indicate that 17β-estradiol intravitreal administration protects the function of the rat retina by preventing retinal neuronal apoptosis from light damage. In addition, the PI3K/Akt signaling pathway is activated, which inhibits caspase-3 activation and induces NF-κB p65 nuclear translocation.
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Evidence is emerging for a role of rough endoplasmic reticulum (RER) in the form of stress granules, the unfolded protein response and protein bodies in the response of neurons to injury and in neurodegenerative diseases. Here, we have studied the role of the peripheral target in regulating the RER and polyribosomes of Nissl bodies in axotomised adult cat dorsal root ganglion (DRG) neurons where axonal regeneration and peripheral target reinnervation was either allowed or denied. Retrograde labelling with horseradish peroxidise was used as an independent marker to enable selection of only those DRG neuronal cell bodies with axons in the injured intercostal nerves. ⋯ This was not seen after axotomy with reinnervation denied. We propose that the target-dependent changes in Nissl body ultrastructure described here are part of a continuum that can modify neuronal protein synthesis directed towards growth, maintenance or death of the neuron. This represents a possible structural basis for mediating the varied effects of neurotrophic interactions.