The dystonias are a group of disorders characterized by involuntary twisting movements and abnormal posturing. The most common of the inherited dystonias is DYT1 dystonia, which is due to deletion of a single GAG codon (ΔE) in the TOR1A gene that encodes torsinA. Since some forms of dystonia have been linked with dysfunction of brain dopamine pathways, the integrity of these pathways was explored in a knock-in mouse model of DYT1 dystonia. In DYT1(ΔE) knock-in mice, neurochemical measures revealed only small changes in the content of dopamine or its metabolites in tissue homogenates from caudoputamen or midbrain, but microdialysis studies revealed robust decreases in baseline and amphetamine-stimulated extracellular dopamine in the caudoputamen. Quantitative stereological methods revealed no evidence for striatal or midbrain atrophy, but substantia nigra neurons immunopositive for tyrosine hydroxylase were slightly reduced in numbers and enlarged in size. Behavioral studies revealed subtle abnormalities in gross motor activity and motor coordination without overt dystonia. Neuropharmacological challenges of dopamine systems revealed normal behavioral responses to amphetamine and a minor increase in sensitivity to haloperidol. These results demonstrate that this DYT1(ΔE) knock-in mouse model of dystonia harbors neurochemical and structural changes of the dopamine pathways, as well as motor abnormalities.

The dystonias are comprised of a group of disorders that share common neurological abnormalities of involuntary twisting or repetitive movements and postures. The most common inherited primary dystonia is DYT1 dystonia, which is due to loss of a GAG codon in the TOR1A gene that encodes torsinA. Autopsy studies of brains from patients with DYT1 dystonia have revealed few abnormalities, although recent neuroimaging studies have implied the existence of microstructural defects that might not be detectable with traditional histopathological methods. The current studies took advantage of a knock-in mouse model for DYT1 dystonia to search for subtle anatomical abnormalities in the striatum, a region often implicated in studies of dystonia. Multiple abnormalities were identified using a combination of quantitative stereological measures of immunohistochemical stains for specific neuronal populations, morphometric studies of Golgi-stained neurons, and immuno-electron microscopy of synaptic connectivity. In keeping with other studies, there was no obvious loss of striatal neurons in the DYT1 mutant mice. However, interneurons immunoreactive for choline acetyltransferase or parvalbumin were larger in the mutants than in control mice. In contrast, interneurons immunoreactive for neuronal nitric oxide synthase were smaller in the mutants than in controls. Golgi histochemical studies of medium spiny projection neurons in the mutant mice revealed slightly fewer and thinner dendrites, and a corresponding loss of dendritic spines. Electron microscopic studies showed a reduction in the ratio of axo-spinous to axo-dendritic synaptic inputs from glutamatergic and dopaminergic sources in mutant mice compared with controls. These results suggest specific anatomical substrates for altered signaling in the striatum and potential correlates of the abnormalities implied by human imaging studies of DYT1 dystonia.

It is well known that anti-prion protein (PrP) monoclonal antibodies (mAbs) inhibit abnormal isoform PrP (PrPSc) formation in cell culture. Additionally, passive immunization of anti-PrP mAbs protects the animals from prion infection via peripheral challenge when mAbs are administered simultaneously or soon after prion inoculation. Thus, anti-PrP mAbs are candidates for the treatment of prion diseases. However, the effects of mAbs on disease progression in the middle and late stages of the disease remain unclear. This study carried out intraventricular infusion of mAbs into prion-infected mice before and after clinical onset to assess their ability to delay disease progression. A 4-week infusion of anti-PrP mAbs initiated at 120 days post-inoculation (p.i.), which is just after clinical onset, reduced PrPSc levels to 70–80 % of those found in mice treated with a negative-control mAb. Spongiform changes, microglial activation and astrogliosis in the hippocampus and thalamus appeared milder in mice treated with anti-PrP mAbs than in those treated with a negative-control mAb. Treatment with anti-PrP mAb prolonged the survival of mice infected with Chandler or Obihiro strain when infusion was initiated at 60 days p.i., at which point PrPSc is detectable in the brain. In contrast, infusion initiated after clinical onset prolonged the survival time by about 8 % only in mice infected with the Chandler strain. Although the effects on survival varied for different prion strains, the anti-PrP mAb could partly prevent disease progression, even after clinical onset, suggesting immunotherapy as a candidate for treatment of prion diseases.

Low molecular weight fucoidan (LMF) has been reported to possess anti-inflammatory and antioxidant activities. Thus, we examined the effects of LMF extracted from Undaria pinnatifida on dermal wounds. Five round dermal wounds were created on the dorsal back of rats, and they were then treated topically with distilled water (DW), Madecasol Care™ (MC) or LMF at 200, 100 and 50 mg/mL, twice a day for a week. There were dose-dependent increases in wound contraction in the groups receiving LMF but not in the MC group, compared with the DW. Histopathological examination revealed that LMF treatment accelerated wound healing, which was supported by increases in granular tissue formation on day four post-treatment but a decrease on day seven, accompanied by an evident reduction in inflammatory cells. In the LMF-treated wounds, collagen distribution and angiogenesis were increased in the granular tissue on days four and seven post-treatment. Immunoreactive cells for transforming growth factor-β1, vascular endothelial growth factor receptor-2 or matrix metalloproteinases 9 were also increased, probably due to tissue remodeling. Furthermore, LMF treatment reduced lipid peroxidation and increased antioxidant activities. These suggested that LMF promotes dermal wound healing via complex and coordinated antioxidant, anti-inflammatory and growth factor-dependent activities.

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Osteoarthritis (OA) is a degenerative joint disease caused by articular cartilage loss. Many complementary and alternative medicines for OA have been reported so far, but the effectiveness is controversial. Previously, we have shown anti-inflammatory effects of low level laser therapy with static magnetic field, magnetic infrared laser (MIL), in various animal models. Therefore, the beneficial effects were examined in OA rat model. Rats were divided by six groups; no treatment controls of sham and OA model, three MIL treatment groups of OA model at 6.65, 2.66 and 1.33 J cm(-2), and Diclofenac group of OA model with 2 mg kg(-1) diclofenac sodium. The OA control exhibited typical symptoms of OA, but 4-week MIL treatment improved the functional movement of knee joint with reduced edematous changes. In addition, cartilage GAGs were detected more in all MIL treatment groups than OA control. It suggests that 4-week MIL irradiation has dose-dependent anti-inflammatory and chondroprotective effects on OA. Histopathological analyses revealed that MIL treatment inhibits the cartilage degradation and enhances chondrocyte proliferation. The fact that MIL has an additional potential for the cartilage formation and no adverse effects can be regarded as great advantages for OA treatment. These suggest that MIL can be useful for OA treatment.

Acupuncture is a treatment option for dry eye syndrome (DES), but its efficacy remains still controversial. We assessed the effectiveness of this treatment for typical DES without specific aetiologies. Eight databases up through June 2018 were searched for randomized clinical trials (RCTs) comparing treatments of acupuncture with artificial tears. The risk of bias was assessed using Cochrane criteria, and a random effects model was used for meta‐analyses on tear‐film breakup time (BUT), Schirmer test, corneal fluorescein staining (CFS), ocular surface disease index, visual analogue scale and score of symptoms (SOS). Subgroup and sensitivity analyses were conducted to explore the heterogeneity, and publication bias was assessed by funnel plot using Egger’s test. Twenty‐one RCTs in 19 studies (n = 1542 eyes) met our eligible criteria. The results demonstrated the superiority of acupuncture in improving the symptoms of BUT, Schirmer test, CFS and SOS, compared to artificial tears acting alone. The BUT and Schirmer test were also more improved in acupuncture combination with artificial tears than artificial tears alone. Further subgroup analyses suggest that acupuncture applied at 2.0–3.0 times per week for 21–30 days may be optimal for treating typical DES. This provides useful information for guiding acupuncture in the clinical trials.

The dystonias are a group of disorders characterized by involuntary twisting and repetitive movements. DYT1 dystonia is an inherited form of dystonia caused by a mutation in the TOR1A gene, which encodes torsinA. TorsinA is expressed in many regions of the nervous system, and the regions responsible for causing dystonic movements remain uncertain. Most prior studies have focused on the basal ganglia, although there is emerging evidence for abnormalities in the cerebellum too. In the current studies, we examined the cerebellum for structural abnormalities in a knock-in mouse model of DYT1 dystonia. The gross appearance of the cerebellum appeared normal in the mutant mice, but stereological measures revealed the cerebellum to be 5% larger in mutant compared to control mice. There were no changes in the numbers of Purkinje cells, granule cells, or neurons of the deep cerebellar nuclei. However, Golgi histochemical studies revealed Purkinje cells to have thinner dendrites, and fewer and less complex dendritic spines. There also was a higher frequency of heterotopic Purkinje cells displaced into the molecular layer. These results reveal subtle structural abnormalities of the cerebellum that are similar to those reported for the basal ganglia in the DYT1 knock-in mouse model.