Gabapentin treatment improves motor coordination in a mice model of progressive ataxia.
No causal treatment of ataxias is available at the moment, and so symptomatic and disease-modifying therapies are regarded as a reliable possibility for this complex group of movement disorders. In order to explore possible pharmacological strategies aimed at interfering with ataxia development or progression, we used HCN1-/- mice. Mice carrying the deletion of the gene encoding for the voltage-dependent K-channel (HCN1-/-) have a normal basic motor function, but impaired learning of the motor skills that enable mice to balance on the rotating rod. In this study we showed that the motor coordination impairment observed in HCN1-/- mice is paralleled by a decline of GABA content in the cerebellum. Treatment with the GABA mimetic gabapentin at prenatal age prevents full development of the ataxia symptom. This result could have implications for possible therapeutic strategies aimed at more effective coupling with ataxia in several neurological diseases in which this symptom develops and is prominent over time. In view of its long-lasting effect, it could be also considered as a disease-modifying drug.
Massella
Alessandro
A
BioPharmaNet-DIMORFIPA, University of Bologna, Ozzano Emilia, Italy.
Gusciglio
Marco
M
D'Intino
Giulia
G
Sivilia
Sandra
S
Ferraro
Luca
L
Calzà
Laura
L
Giardino
Luciana
L
D000367:Age Factors; D000588:Amines / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001259:Ataxia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D001284:Atrophy / Q000473:pathology; D002452:Cell Count; D002531:Cerebellum / Q000737:chemistry / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002851:Chromatography, High Pressure Liquid; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D000077206:Gabapentin; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D051379:Mice; D018345:Mice, Knockout; D009048:Motor Skills / Q000187:drug effects*; D015221:Potassium Channels / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045442:Rotarod Performance Test; D013194:Staining and Labeling; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000494:pharmacology*
D000588:Amines; D054815:Cyclic Nucleotide-Gated Cation Channels; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; C578666:Hcn1 protein, mouse; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels; D012333:RNA, Messenger; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1