Experimental neurology
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Experimental neurology · Jan 2014
Age-related impairment of olfactory bulb neurogenesis in the Ts65Dn mouse model of Down syndrome.
Down syndrome (DS) is a genetic condition caused by triplication of chromosome 21. Widespread neurogenesis reduction during brain development underlies the numerous neurological defects of DS. These defects start to manifest themselves at birth and worsen with age. ⋯ In mid-age (13-month-old) Ts65Dn mice, however, the proliferation rate in the SVZ was more severely reduced in comparison with euploid mice and the number of neuroblasts in the RMS and new granule neurons added to the OB underwent a reduction. While in young Ts65Dn mice the olfactory function, assessed with the buried food pellet test, was similar to that of euploid mice, in mid-age mice it was significantly impaired. Taken together, results suggest that an age-related reduction in the renewal of OB granule cells may underlie the age-related smell impairment in DS.
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Experimental neurology · Jan 2014
Nitro-oleic acid desensitizes TRPA1 and TRPV1 agonist responses in adult rat DRG neurons.
Nitro-oleic acid (OA-NO2), an electrophilic fatty acid nitroalkene byproduct of redox reactions, activates transient receptor potential ion channels (TRPA1 and TRPV1) in primary sensory neurons. To test the possibility that signaling actions of OA-NO2 might modulate TRP channels, we examined: (1) interactions between OA-NO2 and other agonists for TRPA1 (allyl-isothiocyanate, AITC) and TRPV1 (capsaicin) in rat dissociated dorsal root ganglion cells using Ca(2+) imaging and patch clamp techniques and (2) interactions between these agents on sensory nerves in the rat hindpaw. Ca(2+) imaging revealed that brief application (15-30 s) of each of the three agonists induced homologous desensitization. ⋯ Homologous desensitization occurred with AITC and capsaicin when applied at 15 minute intervals, but did not occur with OA-NO2 when applied at a 30 min interval. Pretreatment with OA-NO2 reduced AITC-evoked nociceptive behaviors but did not alter capsaicin responses. These results raise the possibility that OA-NO2 might be useful clinically to reduce neurogenic inflammation and certain types of painful sensations by desensitizing TRPA1 expressing nociceptive afferents.
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Experimental neurology · Jan 2014
Kv2 dysfunction after peripheral axotomy enhances sensory neuron responsiveness to sustained input.
Peripheral nerve injuries caused by trauma are associated with increased sensory neuron excitability and debilitating chronic pain symptoms. Axotomy-induced alterations in the function of ion channels are thought to largely underlie the pathophysiology of these phenotypes. Here, we characterise the mRNA distribution of Kv2 family members in rat dorsal root ganglia (DRG) and describe a link between Kv2 function and modulation of sensory neuron excitability. ⋯ In accordance with a shortened AHP, ScTx treatment also reduced the refractory period and improved AP conduction to the cell soma during high frequency stimulation. These results suggest that Kv2 downregulation following traumatic nerve lesion facilitates greater fidelity of repetitive firing during prolonged input and thus normal Kv2 function is postulated to limit neuronal excitability. In summary, we have profiled Kv2 expression in sensory neurons and provide evidence for the contribution of Kv2 dysfunction in the generation of hyperexcitable phenotypes encountered in chronic pain states.