Adenosine Kinase Deficiency in the Brain Results in Maladaptive Synaptic Plasticity.

ABSTRACT: Adenosine kinase (ADK) deficiency in human patients (OMIM:614300) disrupts the methionine cycle and triggers hypermethioninemia, hepatic encephalopathy, cognitive impairment, and seizures. To identify whether this neurological phenotype is intrinsically based on ADK deficiency in the brain or if it is secondary to liver dysfunction, we generated a mouse model with a brain-wide deletion of ADK by introducing a Nestin-Cre transgene into a line of conditional ADK deficient Adk^fl/fl mice. These Adk^Δbrain mice developed a progressive stress-induced seizure phenotype associated with spontaneous convulsive seizures and profound deficits in hippocampus-dependent learning and memory. Pharmacological, biochemical, and electrophysiological studies suggest enhanced adenosine leve

SUBMITTER: Sandau US 

PROVIDER: S-EPMC5148215 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature