Neuroscience
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Spinal cord stimulation (SCS) is used clinically to treat neuropathic pain states, but the precise mechanism by which it attenuates neuropathic pain remains to be established. The profile of afferent fiber activation during SCS and how it may correlate with the efficacy of SCS-induced analgesia are unclear. After subjecting rats to an L5 spinal nerve ligation (SNL), we implanted a miniature quadripolar electrode similar to that used clinically. ⋯ Results showed that three consecutive days of SCS treatment (50 Hz, 0.2 ms, 30 min, 80-90% of MoT), but not sham stimulation, gradually alleviated mechanical hypersensitivity in SNL rats. The MoT obtained in the animal behavioral study was significantly less than the Aα/β-threshold of the compound AP determined during electrophysiological recording, suggesting that SCS could attenuate mechanical hypersensitivity with a stimulus intensity that recruits only a small fraction of the A-fiber population in SNL rats. Although both the MoT and compound AP threshold were similar between responders and nonresponders, the size of the compound AP waveform at higher stimulation intensities was larger in the responders, indicating a more efficient activation of the dorsal column structure in responders.
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Mutations in parkin were first identified in a group of Japanese patients who developed autosomal recessive juvenile Parkinsonism with clinical symptoms similar to idiopathic Parkinson's disease (PD). Parkin is an E3 ligase that targets a number of substrates for ubiquitination. ⋯ We found that p32 can regulate mitochondrial morphology and dynamics by promoting parkin degradation through autophagy. These results suggest that parkin might be an important effector in the regulation of morphology and dynamics of mitochondria.
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In the present study, orexinergic cell bodies within the brains of rhythmic and arrhythmic circadian chronotypes from three species of African mole rat (Highveld mole rat-Cryptomys hottentotus pretoriae, Ansell's mole rat--Fukomys anselli and the Damaraland mole rat--Fukomys damarensis) were identified using immunohistochemistry for orexin-A. Immunopositive orexinergic (Orx+) cell bodies were stereologically assessed and absolute numbers of orexinergic cell bodies were determined for the distinct circadian chronotypes of each species of mole rat examined. ⋯ These differences were observed when the raw data was compared and when the raw data was corrected for body mass (M(b)) and brain mass (M(br)). For the two other species investigated, no significant differences were noted between the chronotypes, although a statistically significant difference was noted between all rhythmic and arrhythmic individuals of the current study when the counts of orexin neurons were corrected for M(b)--the arrhythmic individuals had larger numbers of orexin cells.
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The timeline of dopamine (DA) system maturation and the signaling properties of DA receptors (DRs) during rat brain development are not fully characterized. We used in situ hybridization and quantitative PCR to map DR mRNA transcripts in the medial frontal cortex (mFC) and striatum (STR) of the rat from embryonic day (E) 15 to E21. The developmental trajectory of DR mRNAs revealed distinct patterns of DA receptors 1 and 2 (DRD1, DRD2) in these brain regions. ⋯ DR-mediated signaling cascades were functional in E15 cultures in both brain regions. Because DA fibers do not reach the mFC by E15, and DA was not present in cultures, these data indicate that DRs can become functional in the absence of DA innervation. Because activation of DR signal transduction pathways can affect network organization of the developing brain, maternal exposure to drugs that affect DR activity may be liable to interfere with fetal brain development.
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Dopamine (DA) is a key transmitter in the basal ganglia, yet DA transmission does not conform to several aspects of the classic synaptic doctrine. Axonal DA release occurs through vesicular exocytosis and is action potential- and Ca²⁺-dependent. However, in addition to axonal release, DA neurons in midbrain exhibit somatodendritic release by an incompletely understood, but apparently exocytotic, mechanism. ⋯ Mechanistic studies using similar methods in vitro have revealed local regulation of DA release by other transmitters and modulators, as well as by proteins known to be disrupted in Parkinson's disease and other movement disorders. Notably, the actions of most other striatal transmitters on DA release also do not conform to the synaptic doctrine, with the absence of direct synaptic contacts for glutamate, GABA, and acetylcholine (ACh) on striatal DA axons. Overall, the findings reviewed here indicate that DA signaling in the basal ganglia is sculpted by cooperation between the timing and pattern of DA input and those of local regulatory factors.