Histone deacetylase inhibitors improve learning consolidation in young and in KA-induced-neurodegeneration and SAMP-8-mutant mice.
Histone deacetylases (HDAC) are enzymes that maintain chromatin in a condensate state, related with absence of transcription. We have studied the role of HDAC on learning and memory processes. Both eyeblink classical conditioning (EBCC) and object recognition memory (ORM) induced an increase in histone H3 acetylation (Ac-H3). Systemic treatment with HDAC inhibitors improved cognitive processes in EBCC and in ORM tests. Immunohistochemistry and gene expression analyses indicated that administration of HDAC inhibitors decreased the stimulation threshold for Ac-H3, and gene expression to reach the levels required for learning and memory. Finally, we evaluated the effect of systemic administration of HDAC inhibitors to mice models of neurodegeneration and aging. HDAC inhibitors reversed learning and consolidation deficits in ORM in these models. These results point out HDAC inhibitors as candidate agents for the palliative treatment of learning and memory impairments in aging and in neurodegenerative disorders.
Fontán-Lozano
Angela
A
División de Neurociencias, Universidad Pablo de Olavide de Sevilla, Sevilla, Spain.
Romero-Granados
Rocío
R
Troncoso
Julieta
J
Múnera
Alejandro
A
Delgado-García
José María
JM
Carrión
Angel M
AM
D000107:Acetylation / Q000187:drug effects; D000375:Aging / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000187:drug effects; D001767:Blinking / Q000187:drug effects; D003214:Conditioning, Classical / Q000187:drug effects*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000627:therapeutic use; D007608:Kainic Acid; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D010364:Pattern Recognition, Visual / Q000187:drug effects; D013997:Time Factors
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A; D007608:Kainic Acid