title: Hippocampus-dependent spatial learning and memory are impaired in growth hormone-deficient spontaneous dwarf rats.
abstract: Growth hormone (GH)/insulin-like growth factor-I deficiencies are known to cause alterations in brain development resulting in impairment of cognitive function. In order to investigate the behavioral phenotype of GH-deficient spontaneous dwarf rats (SDRs), we examined the behavior of the SDRs in the Morris water maze and Y-maze tasks. The SDRs showed severe deficits in spatial learning and memory compared to normal rats. The possibility that the cognitive impairment is associated with alteration of neurotransmitter systems was examined histologically following completion of the behavioral tests, using choline acetyltransferase (ChAT), vesicular glutamate transporter 1 (VGlut1) and glutamic acid decarboxylase (GAD6) immunohistochemistry as markers. In the SDRs the number of ChAT-stained basal forebrain cholinergic neurons was decreased. ChAT staining was also decreased in the hippocampus, one of the target areas of basal forebrain cholinergic neurons. Next, we examined the number of glutamatergic and GABAergic boutons in the hippocampal molecular layer and found a significant reduction in the density of VGlut1+ boutons and an increase in GAD6+ profiles, leading to a significantly reduced ratio in glutamatergic/GABAergic synapses. Finally, the number of newly generated cells in the subgranular zone of the hippocampus was significantly lower than in normal rats. Taken together, our data suggest that GH is an important regulator of hippocampus-dependent spatial learning and memory. The behavioral deficits in the SDRs may be explained by altered basal forebrain cholinergic innervation, imbalance in hippocampal glutamatergic/GABAergic synapses, and decreased neurogenesis in the hippocampus.
authors.affiliation: Department of Pharmacology and Medical Research Center for Bioreaction to ROS and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Endan
authors.initials: E
authors.lastname: Li
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Mudan
authors.initials: M
authors.lastname: Cai
authors.forename: Sungyoub
authors.initials: S
authors.lastname: Lee
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kim
authors.forename: Eunjin
authors.initials: E
authors.lastname: Lim
authors.forename: Jong
authors.initials: J
authors.lastname: Hoon Ryu
authors.forename: Terry G
authors.initials: TG
authors.lastname: Unterman
authors.forename: Seungjoon
authors.initials: S
authors.lastname: Park
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004393:Dwarfism, Pituitary / Q000503:physiopathology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D005971:Glutamates / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology; D051381:Rats; D013569:Synapses / Q000502:physiology; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D005971:Glutamates; C493466:Slc17a7 protein, rat; D050598:Vesicular Glutamate Transport Protein 1; D005680:gamma-Aminobutyric Acid; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D000109:Acetylcholine