A new knock-in mouse model of l-DOPA-responsive dystonia.

Abnormal dopamine neurotransmission is associated with many different genetic and acquired dystonic disorders. For instance, mutations in genes critical for the synthesis of dopamine, including GCH1 and TH cause l-DOPA-responsive dystonia. Despite evidence that implicates abnormal dopamine neurotransmission in dystonia, the precise nature of the pre- and postsynaptic defects that result in dystonia are not known. To better understand these defects, we generated a knock-in mouse model of l-DOPA-responsive dystonia (DRD) mice that recapitulates the human p.381Q>K TH mutation (c.1141C>A). Mice homozygous for this mutation displayed the core features of the human disorder, including reduced TH activity, dystonia that worsened throughout the course of the active phase, and improvement in the dystonia in response to both l-DOPA and trihexyphenidyl. Although the gross anatomy of the nigrostriatal dopaminergic neurons was normal in DRD mice, the microstructure of striatal synapses was affected whereby the ratio of axo-spinous to axo-dendritic corticostriatal synaptic contacts was reduced. Microinjection of l-DOPA directly into the striatum ameliorated the dystonic movements but cerebellar microinjections of l-DOPA had no effect. Surprisingly, the striatal dopamine concentration was reduced to ∼1% of normal, a concentration more typically associated with akinesia, suggesting that (mal)adaptive postsynaptic responses may also play a role in the development of dystonia. Administration of D1- or D2-like dopamine receptor agonists to enhance dopamine signalling reduced the dystonic movements, whereas administration of D1- or D2-like dopamine receptor antagonists to further reduce dopamine signalling worsened the dystonia, suggesting that both receptors mediate the abnormal movements. Further, D1-dopamine receptors were supersensitive; adenylate cyclase activity, locomotor activity and stereotypy were exaggerated in DRD mice in response to the D1-dopamine receptor agonist SKF 81297. D2-dopamine receptors exhibited a change in the valence in DRD mice with an increase in adenylate cyclase activity and blunted behavioural responses after challenge with the D2-dopamine receptor agonist quinpirole. Together, our findings suggest that the development of dystonia may depend on a reduction in dopamine in combination with specific abnormal receptor responses.

Low-temperature synthesis and photocatalytic activity of TiO2 pillared montmorillonite.

TiO2 pillared montmorillonite (PILM) was synthesized by hydrolyzing TiO2 sol into the interlayers of montmorillonite (MMT) at low temperatures. It is novel that all the as-prepared catalysts without calcination show a high photocatalytic activity for the degradation of acid red G (ARG) under UV light irradiation. The as-prepared powders were characterized by XRD, TEM, UV-vis diffuse reflectance spectroscopy, BET, and FT-IR. The X-ray diffraction analysis indicated that the (001) plane of MMT in the composites disappeared and that the layered structure became disordered, which also was confirmed by the TEM photographs. The UV absorption edge of the composites shows a red-shift in comparison to that of pure TiO2 particles. The obtained catalyst has the highest photocatalytic activity when the composite temperature is 70 degrees C, which could be attributed to the synergetic effects of the adsorbability of MMT and the photocatalytic property of TiO2 in it.