Dysregulation of synaptic proteins, dendritic spine abnormalities and pathological plasticity of synapses as experience-dependent mediators of cognitive and psychiatric symptoms in Huntington’s disease

• Published in: Neuroscience Vol. 251; pp. 66 - 74
• Main Authors: Nithianantharajah, J, Hannan, A.J
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 22.10.2013
• Subjects: Animals; Brain - pathology; Cognition; cognitive deficits; Dendritic Spines - pathology; Disease Models, Animal; Humans; Huntington Disease - pathology; Huntington Disease - psychology; Huntington’s disease; Membrane Proteins - metabolism; Mice; Neurology; Neuronal Plasticity; polyglutamine disease; psychiatric disorders; Synapses - pathology; synaptic plasticity; tandem repeat expansion disorder; yeast artificial chromosome; LTP; cognitive deficits; huntingtin; Huntington’s disease; brain-derived neurotrophic factor; EE; PSD; postsynaptic density; BDNF; long-term depression; CAG; htt; environmental enrichment; F-actin; cytosine-adenine-guanine trinucleotide; actin filaments; YAC; tandem repeat expansion disorder; synaptic plasticity; HD; LTD; long-term potentiation; polyglutamine disease; psychiatric disorders
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2012.05.043

Highlights ► Transgenic mouse models of Huntington’s disease (HD) exhibit abnormalities at dendritic spines and synapses. ► Evidence for HD as a ‘synaptopathy’ can be found at molecular, physiological and structural levels. ► Molecular changes in pre and postsynaptic proteins precede structural abnormalities in dendrites. ► Synaptic abnormalities are experience-dependent and correlated with cognitive and psychiatric symptoms. ► Evidence from HD mice suggests that aberrant plasticity of synapses induces cognitive deficits.