Prenatal Cannabinoid Exposure Elicits Memory Deficits Associated with Reduced PSA-NCAM Expression, Altered Glutamatergic Signaling, and Adaptations in Hippocampal Synaptic Plasticity

Author:

Pinky Priyanka D.12,Bloemer Jenna13ORCID,Smith Warren D.1,Du Yifeng1,Heslin Ryan T.1,Setti Sharay E.1,Pfitzer Jeremiah C.1,Chowdhury Kawsar1ORCID,Hong Hao4,Bhattacharya Subhrajit156,Dhanasekaran Muralikrishnan17ORCID,Dityatev Alexander578ORCID,Reed Miranda N.15ORCID,Suppiramaniam Vishnu15

Affiliation:

1. Department of Drug Discovery and Development, Auburn University, Auburn, AL 36849, USA

2. Department of Biomedical Engineering, University of California Irvine, Irvine, CA 92697, USA

3. Department of Pharmaceutical and Biomedical Sciences, Touro College of Pharmacy, New York, NY 10036, USA

4. Key Laboratory of Neuropsychiatric Diseases, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China

5. Center for Neuroscience Initiative, Auburn University, Auburn, AL 36849, USA

6. Keck Graduate Institute, School of Pharmacy and Health Sciences, Claremont Colleges, Claremont, CA 91711, USA

7. Molecular Neuroplasticity, German Center for Neurodegenerative Diseases (DZNE), 37075 Magdeburg, Germany

8. Medical Faculty, Otto-von-Guericke University, 39106 Magdeburg, Germany

Abstract

Cannabis is now one of the most commonly used illicit substances among pregnant women. This is particularly concerning since developmental exposure to cannabinoids can elicit enduring neurofunctional and cognitive alterations. This study investigates the mechanisms of learning and memory deficits resulting from prenatal cannabinoid exposure (PCE) in adolescent offspring. The synthetic cannabinoid agonist WIN55,212-2 was administered to pregnant rats, and a series of behavioral, electrophysiological, and immunochemical studies were performed to identify potential mechanisms of memory deficits in the adolescent offspring. Hippocampal-dependent memory deficits in adolescent PCE animals were associated with decreased long-term potentiation (LTP) and enhanced long-term depression (LTD) at hippocampal Schaffer collateral-CA1 synapses, as well as an imbalance between GluN2A- and GluN2B-mediated signaling. Moreover, PCE reduced gene and protein expression of neural cell adhesion molecule (NCAM) and polysialylated-NCAM (PSA-NCAM), which are critical for GluN2A and GluN2B signaling balance. Administration of exogenous PSA abrogated the LTP deficits observed in PCE animals, suggesting PSA mediated alterations in GluN2A- and GluN2B- signaling pathways may be responsible for the impaired hippocampal synaptic plasticity resulting from PCE. These findings enhance our current understanding of how PCE affects memory and how this process can be manipulated for future therapeutic purposes.

Funder

National Institute on Drug Abuse

Publisher

MDPI AG

Subject

General Medicine

Reference94 articles.

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