Το προσυνέδριο της IFLA στην Αθήνα, 19-21 Αυγούστου 2009

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Identification of <i>trm2</i> mutation.

<p>A: Distribution of haplotypes around <i>trm2</i> in (TRM × TRMR)F1 × TRM backcross progeny. White boxes, animals heterozygous for TRM alleles. Black boxes, animals homozygous for TRM alleles. Number of backcross progeny specified underneath the haplotypes. B: Linkage and physical maps including <i>trm2</i>. <i>Parp8</i>, poly (ADP-ribose) polymerase family, member 8; <i>Emb</i>, embigin; <i>Mrps30</i>, mitochondrial ribosomal protein S30; <i>Fgf10</i>, fibroblast growth factor 10. C: Sequencing analysis in TRMR (upper) and TRM (lower) rats. A nucleotide change from C to T located in <i>Hcn1</i> exon 4 is indicated by arrow. The mutation results in an amino acid substitution of alanine (Ala) with valine (Val) at codon 354 of the HCN1 protein. D: Schematic representation of the HCN1 channel subunit. P-loop, pore region; CNBD, cyclic nucleotide-binding domain; black circle, A354V substitution located in the pore region. E: Representative current recordings of wild-type and A354V HCN1 channels. Right panel, hyperpolarization-induced currents measured at the end of the step pulse (-120 mV). Data are presented as the mean ± SEM of seven (wild-type) or six (A354V) experiments. **<i>P</i><0.01 <i>vs</i>. wild-type.</p

TRM rat as a model of essential tremor.

<p>A: Representative EMG from TRM rats. Tremor is shown as a bold line above EMG. Lower panels show magnified EMG and its power frequency analysis (red bar). Calibration: 100 μV and 20 s (upper panel), 50 μV and 5 s (lower panel). B: Effects of anti-tremor agents on tremor incidence in TRM rats. Data are presented as the mean ± SEM of seven (propranolol and trihexyphenidyl) or six (phenobarbital) animals. *<i>P</i><0.05, **<i>P</i><0.01, <i>vs</i>. pre-drug control levels (pre).</p

Tremor induction by the HCN1 channel blocker ZD7288 in TRMR rats.

<p>A: Genetic components responsible for tremor development in our rat model of ET. TRM rats, carrying both the <i>tm</i> deletion (red) and the <i>Hcn1</i> mutation (blue), showed body tremors. TRMR rats, carrying the <i>tm</i> deletion but not the <i>Hcn1</i> mutation, showed no body tremors, but body tremors were induced when the selective HCN1 channel blocker ZD7288 was administered (see B, this figure). WTC rats, carrying the <i>Hcn1</i> mutation but not the <i>tm</i> deletion, showed no body tremors with or without administration of ZD7288 (see B, this figure). B: Effects of ZD7288 on tremor induction in nontremulous TRMR rats. Duration and intensity of tremor observed in TRMR rats that received vehicle or ZD7288. Data are presented as the mean ± SEM of seven (vehicle) or eight (ZD7288) animals. *<i>P</i><0.05, **<i>P</i><0.01 <i>vs</i>. pre-treatment control levels (pre).</p

Immunohistochemical analysis of Fos expression in TRM rats.

<p>A: Schematic illustrations of brain sections selected for quantitative analysis of Fos-immunoreactivity. Anteroposterior distance from bregma is shown above each brain section. Filled boxes in each section indicate the areas analyzed. B: Numbers of Fos-immunoreactive neurons in various brain regions. Data show the mean ± SEM of four (TRM) or five (WTC) rats. *<i>P</i><0.05, **<i>P</i><0.01 <i>vs</i>. control (WTC).</p

Tremor inhibition by IO lesioning in TRM rats.

<p>A: Effects of IO lesioning on tremor induction in TRM rats. The duration and intensity of tremor was significantly suppressed 38 and 54 h after IO lesioning. Data are presented as the mean ± SEM of five animals. *<i>P</i><0.05 <i>vs</i>. pre-treatment control. B: Lesion sites in the brain sections.</p

Identification of <i>trm2</i> mutation.

<p>A: Distribution of haplotypes around <i>trm2</i> in (TRM × TRMR)F1 × TRM backcross progeny. White boxes, animals heterozygous for TRM alleles. Black boxes, animals homozygous for TRM alleles. Number of backcross progeny specified underneath the haplotypes. B: Linkage and physical maps including <i>trm2</i>. <i>Parp8</i>, poly (ADP-ribose) polymerase family, member 8; <i>Emb</i>, embigin; <i>Mrps30</i>, mitochondrial ribosomal protein S30; <i>Fgf10</i>, fibroblast growth factor 10. C: Sequencing analysis in TRMR (upper) and TRM (lower) rats. A nucleotide change from C to T located in <i>Hcn1</i> exon 4 is indicated by arrow. The mutation results in an amino acid substitution of alanine (Ala) with valine (Val) at codon 354 of the HCN1 protein. D: Schematic representation of the HCN1 channel subunit. P-loop, pore region; CNBD, cyclic nucleotide-binding domain; black circle, A354V substitution located in the pore region. E: Representative current recordings of wild-type and A354V HCN1 channels. Right panel, hyperpolarization-induced currents measured at the end of the step pulse (-120 mV). Data are presented as the mean ± SEM of seven (wild-type) or six (A354V) experiments. **<i>P</i><0.01 <i>vs</i>. wild-type.</p