Hippocampus-dependent spatial learning and memory are impaired in growth hormone-deficient spontaneous dwarf rats

Endocrine Journal

Eunjin Lim²  Jong Hoon Ryu¹  Mudan Cai¹  Endan Li²  Sungyoub Lee²  Dong Hyun Kim¹  Yumi Kim²  Seungjoon Park²  Terry G Unterman³ 

[1] Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul, Korea;Department of Pharmacology and Medical Research Center for Bioreaction to ROS and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Korea;Departments of Medicine and Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, and Jesse Brown VA Medical Center, Chicago, IL, USA

关键词: Growth hormone;    Insulin-like growth factor I;    Cognitive function;    Spontaneous dwarf rat;    Forebrain cholinergic neurons;   

DOI  :  10.1507/endocrj.K11E-006

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(47)Cited-By(14)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.

【 授权许可】

Unknown