Impairment of synaptic development in the hippocampus of diabetic Goto-Kakizaki rats

Autor: Tomoko Tashiro, Erika Sawano, Yuki Matsunaga, Takayuki Negishi, Yuta Kawagoe, Akinori Hatakeyama
Rok vydání: 2016
Předmět:
0301 basic medicine
Blood Glucose
Male
medicine.medical_treatment
Hippocampus
Cyclophilins
0302 clinical medicine
Mutation Rate
Postsynaptic potential
Insulin
Pyrophosphatases
Age Factors
Intracellular Signaling Peptides and Proteins
Gene Expression Regulation
Developmental
Excitatory postsynaptic potential
NMDA receptor
Disks Large Homolog 4 Protein
Locomotion
medicine.medical_specialty
Biology
Receptors
N-Methyl-D-Aspartate
Statistics
Nonparametric
03 medical and health sciences
Insulin resistance
Developmental Neuroscience
Internal medicine
medicine
Animals
Rats
Wistar
Maze Learning
Phosphoric Diester Hydrolases
Body Weight
Membrane Proteins
medicine.disease
Receptor
Insulin
Rats
Insulin receptor
Disease Models
Animal
030104 developmental biology
Endocrinology
Animals
Newborn
Diabetes Mellitus
Type 2
Synaptic plasticity
Synapses
Vesicular Glutamate Transport Protein 1
biology.protein
Proto-Oncogene Proteins c-akt
030217 neurology & neurosurgery
Developmental Biology
Zdroj: International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience. 53
ISSN: 1873-474X
Popis: Insulin receptor signaling has been shown to regulate essential aspects of CNS function such as synaptic plasticity and neuronal survival. To elucidate its roles during CNS development in vivo, we examined the synaptic and cognitive development of the spontaneously diabetic Goto-Kakizaki (GK) rats in the present study. GK rats are non-obese models of type 2 diabetes established by selective inbreeding of Wistar rats based on impaired glucose tolerance. Though they start exhibiting only moderate hyperglycemia without changes in plasma insulin levels from 3 weeks postnatally, behavioral alterations in the open-field as well as significant impairments in memory retention compared with Wistar rats were observed at 10 weeks and were worsened at 20 weeks. Alterations in insulin receptor signaling and signs of insulin resistance were detected in the GK rat hippocampus at 3 weeks, as early as in other insulin-responsive peripheral tissues. Significant reduction of an excitatory postsynaptic scaffold protein, PSD95, was found at 5w and later in the hippocampus of GK rats due to the absence of a two-fold developmental increase of this protein observed in Wistar control rats between 3 and 20w. In the GK rat hippocampus, NR2A which is a NMDA receptor subunit selectively anchored to PSD95 was also reduced. In contrast, both NR2B and its anchoring protein, SAP102, showed similar developmental profiles in Wistar and GK rats with expression peaks at 2 and 3w. The results suggest that early alterations in insulin receptor signaling in the GK rat hippocampus may affect cognitive performance by suppressing synaptic maturation.
Databáze: OpenAIRE
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