Type 1 diabetes mellitus in mice increases hippocampal d-serine in the acute phase after streptozotocin injection

Masataka Suzuki, Jumpei Sasabe, Shigeki Furuya, Masashi Mita, Kenji Hamase, Sadakazu Aiso

Research output: Contribution to journalArticle

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Abstract

Diabetes mellitus (DM) is known to be a risk factor in the development of deficits in cognition, learning, and memory. In DM animal models, including the streptozotocin (STZ)-induced diabetic rodent model, abnormalities in the regulation of several neurotransmitters have been reported. However, the role in DM of d-serine, an endogenous co-agonist of glutamatergic N-methyl-d-aspartate receptors, remains unknown. Here, we measured the amounts of d-/l-serine and l-glutamate in the hippocampi of STZ-treated mice using a 2D-HPLC system from acute to chronic phases after the induction of DM. STZ treatment significantly increased the d-serine level by 23.7% in the hippocampus compared with vehicle treatment at 1 week after the injection, whereas it did not affect the levels of l-serine. In contrast, l-glutamate levels in the hippocampus were elevated at 3 days after STZ injection and rather decreased at 1 week after that. Such alterations in the amino acids were not evident in the chronic phases. We further tested whether the STZ-induced d-serine increase was caused by DM pathophysiology. In vivo, subcutaneous insulin implants into STZ-treated mice restored the elevated d-serine levels in the hippocampus. An in vitro study using primary cultured hippocampal neurons revealed that treatments of STZ did not directly affect the level of d-serine secreted in the cultured media. These results indicate that DM pathology caused by insulin deficiency triggers transient d-serine increase and l-glutamate alteration in the hippocampus. Such aberrant regulations of excitatory neurotransmitters may be relevant to the formation of DM-related dysfunction of the central nervous system (CNS).

Original languageEnglish
Pages (from-to)167-176
Number of pages10
JournalBrain Research
Volume1466
DOIs
Publication statusPublished - Jul 23 2012

Fingerprint

Streptozocin
Type 1 Diabetes Mellitus
Serine
Diabetes Mellitus
Injections
Hippocampus
Glutamic Acid
Neurotransmitter Agents
Insulin
Cognition
Rodentia
Therapeutics
Central Nervous System
Animal Models
High Pressure Liquid Chromatography
Learning
Pathology
Neurons
Amino Acids

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Type 1 diabetes mellitus in mice increases hippocampal d-serine in the acute phase after streptozotocin injection. / Suzuki, Masataka; Sasabe, Jumpei; Furuya, Shigeki; Mita, Masashi; Hamase, Kenji; Aiso, Sadakazu.

In: Brain Research, Vol. 1466, 23.07.2012, p. 167-176.

Research output: Contribution to journalArticle

Suzuki, Masataka ; Sasabe, Jumpei ; Furuya, Shigeki ; Mita, Masashi ; Hamase, Kenji ; Aiso, Sadakazu. / Type 1 diabetes mellitus in mice increases hippocampal d-serine in the acute phase after streptozotocin injection. In: Brain Research. 2012 ; Vol. 1466. pp. 167-176.
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