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Pharmacol Rep. 2021 Aug;73(4):1109-1121. doi: 10.1007/s43440-021-00222-6. Epub 2021 Apr 09.

The pivotal role of pituitary adenylate cyclase-activating polypeptide for lactate production and secretion in astrocytes during fear memory.

Pharmacological reports : PR

Yuki Kambe, Yu Yamauchi, Trung Thanh Nguyen, Thu Thi Nguyen, Yukio Ago, Norihito Shintani, Hitoshi Hashimoto, Shimako Yoshitake, Takashi Yoshitake, Jan Kehr, Namiko Kawamura, Goro Katsuura, Takashi Kurihara, Atsuro Miyata

Affiliations

  1. Department of Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima, 890-8544, Japan.
  2. Department of Cellular and Molecular Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan.
  3. Laboratories of Molecular Neuropharmacology and Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University Medical School, Osaka University, Suita, Osaka, 565-0871, Japan.
  4. Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Suita, Osaka, 565-0871, Japan.
  5. Division of Bioscience, Institute for Datability Science, Osaka University, Suita, Osaka, 565-0871, Japan.
  6. Transdimensional Life Imaging Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Osaka, 565-0871, Japan.
  7. Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden.
  8. Department of Drug Discovery of Next-Generation GcMAF, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima, 890-8544, Japan.
  9. Department of Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima, 890-8544, Japan. [email protected].

PMID: 33835466 DOI: 10.1007/s43440-021-00222-6

Abstract

BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) plays an essential role in the modulation of astrocyte functions. Although lactate secretion from astrocytes contributes to many forms of neuronal plasticity in the central nervous system, including fear learning and memory, the role of PACAP in lactate secretion from astrocytes is unclear.

METHODS: The amygdala and hippocampus of PACAP (+ / +) and PACAP (-/-) mice were acquired 1 h after memory acquisition and recall in the passive avoidance test. The concentration of glycogen and lactate in these regions was measured. The concentration of lactate in the hippocampus's extracellular fluid was also measured by microdialysis during memory acquisition or intracerebroventricular administration of PACAP.

RESULTS: We observed that memory acquisition caused a significant decrease in glycogen concentration and increased lactate concentration in the PACAP (+ / +) mice's hippocampus. However, memory acquisition did not increase in the lactate concentration in PACAP (-/-) mice's hippocampus. Further, memory retrieval evoked lactate production in the amygdala and the hippocampus of PACAP (+ / +) mice. Still, there was no significant increase in lactate concentration in the same regions of PACAP (-/-) mice. In vivo microdialysis in rats revealed that the hippocampus's extracellular lactate concentration increased after a single PACAP intracerebroventricular injection. Additionally, the hippocampus's extracellular lactate concentration increased with the memory acquisition in PACAP (+ / +) mice, but not in PACAP (-/-) mice.

CONCLUSIONS: PACAP may enhance lactate production and secretion in astrocytes during the acquisition and recall of fear memories.

© 2021. Maj Institute of Pharmacology Polish Academy of Sciences.

Keywords: Astrocyte; Fear memory; Glycogen; Lactate; Pituitary adenylate cyclase-activating polypeptide

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