Σάββατο 12 Μαΐου 2018

Neuroprotective and antinociceptive effects of rosemary ( Rosmarinus officinalis L.) extract in rats with painful diabetic neuropathy

Abstract

Diabetes mellitus is associated with the development of neuronal tissue damage in different central and peripheral nervous system regions. A common complication of diabetes is painful diabetic peripheral neuropathy. We have explored the antihyperalgesic and neuroprotective properties of Rosmarinus officinalis L. extract (RE) in a rat model of streptozotocin (STZ)-induced diabetes. The nociceptive threshold and motor coordination of these diabetic rats was assessed using the tail-flick and rotarod treadmill tests, respectively. Activated caspase-3 and the Bax:Bcl-2 ratio, both biochemical indicators of apoptosis, were assessed in the dorsal half of the lumbar spinal cord tissue by western blotting. Treatment of the diabetic rats with RE improved hyperglycemia, hyperalgesia and motor deficit, suppressed caspase-3 activation and reduced the Bax:Bcl-2 ratio, suggesting that the RE has antihyperalgesic and neuroprotective effects in this rat model of STZ-induced diabetes. Cellular mechanisms underlying the observed effects may, at least partially, be related to the inhibition of neuronal apoptosis.

Graphical Abstract



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Impact of non-brain anatomy and coil orientation on inter- and intra-subject variability in TMS at midline

Transcranial magnetic stimulation (TMS) is an established neuromodulation technology that utilizes strong, transient magnetic fields generated by an electromagnetic coil placed on the scalp to induce electric fields in underlying brain tissues (Barker et al. 1985; Walsh and Cowey 2000; Pascual-Leone et al. 1994; Berlim et al. 2014). The strength and distribution of the time-varying magnetic fields are dependent on both the geometry and the amount of current traveling through the TMS coil (Deng et al.

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Heterozygous missense variants of LMX1A lead to nonsyndromic hearing impairment and vestibular dysfunction

Abstract

Unraveling the causes and pathomechanisms of progressive disorders is essential for the development of therapeutic strategies. Here, we identified heterozygous pathogenic missense variants of LMX1A in two families of Dutch origin with progressive nonsyndromic hearing impairment (HI), using whole exome sequencing. One variant, c.721G > C (p.Val241Leu), occurred de novo and is predicted to affect the homeodomain of LMX1A, which is essential for DNA binding. The second variant, c.290G > C (p.Cys97Ser), predicted to affect a zinc-binding residue of the second LIM domain that is involved in protein–protein interactions. Bi-allelic deleterious variants of Lmx1a are associated with a complex phenotype in mice, including deafness and vestibular defects, due to arrest of inner ear development. Although Lmx1a mouse mutants demonstrate neurological, skeletal, pigmentation and reproductive system abnormalities, no syndromic features were present in the participating subjects of either family. LMX1A has previously been suggested as a candidate gene for intellectual disability, but our data do not support this, as affected subjects displayed normal cognition. Large variability was observed in the age of onset (a)symmetry, severity and progression rate of HI. About half of the affected individuals displayed vestibular dysfunction and experienced symptoms thereof. The late-onset progressive phenotype and the absence of cochleovestibular malformations on computed tomography scans indicate that heterozygous defects of LMX1A do not result in severe developmental abnormalities in humans. We propose that a single LMX1A wild-type copy is sufficient for normal development but insufficient for maintenance of cochleovestibular function. Alternatively, minor cochleovestibular developmental abnormalities could eventually lead to the progressive phenotype seen in the families.



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Response to the letter by Dr. Tomoyuki Kawada regarding our manuscript: Independent association between prediabetes and future pancreatic fat accumulation: a 5-year Japanese cohort study



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Prediabetes and subsequent pancreatic fat accumulation



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