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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Endocrinol. | doi: 10.3389/fendo.2019.00819

Adiponectin knockout mice display cognitive and synaptic deficits

 Jenna Bloemer1,  Priyanka D. Pinky1, Warren D. Smith1, Dwipayan Bhattacharya2, Alisa Chauhan1,  Manoj Govindarajulu1, Hao Hong3, Muralikrishnan Dhanasekaran1,  Robert Judd4,  Rajesh H. Amin1,  Miranda N. Reed1* and  Vishnu Suppiramaniam1*
  • 1Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, United States
  • 2Emory Eye Center, United States
  • 3China Pharmaceutical University, China
  • 4Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, United States

Adiponectin is an adipokine that has recently been under investigation for potential neuroprotective effects in various brain disorders including Alzheimer’s disease, stroke, and depression. Adiponectin receptors (AdipoR1 and AdipoR2) are found throughout various brain regions, including the hippocampus. However, the role of these receptors in synaptic and cognitive function is not clear. Therefore, the goal of the current study was to evaluate synaptic and cognitive function in the absence of adiponectin. The current study utilized 12-month old adiponectin knockout (APN-KO) mice and age-matched controls to study cognitive and hippocampal synaptic alterations. We determined that AdipoR1 and AdipoR2 are present in the synaptosome, with AdipoR2 displaying increased presynaptic versus postsynaptic localization, whereas AdipoR1 was enriched in both the presynaptic and postsynaptic fractions. APN-KO mice displayed cognitive deficits in the novel object recognition and Y-maze tests. This was mirrored by deficits in long-term potentiation (LTP) of the hippocampal Schaefer collateral pathway in APN-KO mice. APN-KO mice also displayed a reduction in basal synaptic transmission and an increase in presynaptic release probability. Deficits in LTP were rescued through hippocampal slice incubation with the adiponectin receptor agonist, AdipoRon, indicating that acute alterations in adiponectin receptor signaling influence synaptic function. Along with the deficits in LTP, altered levels of key presynaptic and postsynaptic proteins involved in glutamatergic neurotransmission were observed in APN-KO mice. Taken together, these results indicate that adiponectin is an important regulator of cognition and synaptic function in the hippocampus. Future studies should examine the role of specific adiponectin receptors in synaptic processes.

Keywords: Adiponectin, synaptic plasticity, Cognition, Adiporon, AdipoR1, AdipoR2

Received: 20 Aug 2019; Accepted: 08 Nov 2019.

Copyright: © 2019 Bloemer, Pinky, Smith, Bhattacharya, Chauhan, Govindarajulu, Hong, Dhanasekaran, Judd, Amin, Reed and Suppiramaniam. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mx. Miranda N. Reed, Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849-5506, Alabama, United States, reedmir@auburn.edu
Mx. Vishnu Suppiramaniam, Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849-5506, Alabama, United States, suppivd@auburn.edu