Prenatal Cannabinoid Exposure Elicits Memory Deficits Associated with Reduced PSA-NCAM Expression, Altered Glutamatergic Signaling, and Adaptations in Hippocampal Synaptic Plasticity
Priyanka D. Pinky,
Jenna Bloemer,
Warren D. Smith,
Yifeng Du,
Ryan T. Heslin,
Sharay E. Setti,
Jeremiah C. Pfitzer,
Kawsar Chowdhury,
Hao Hong,
Subhrajit Bhattacharya,
Muralikrishnan Dhanasekaran,
Alexander Dityatev,
Miranda N. Reed,
Vishnu Suppiramaniam
Affiliations
Priyanka D. Pinky
Department of Drug Discovery and Development, Auburn University, Auburn, AL 36849, USA
Jenna Bloemer
Department of Drug Discovery and Development, Auburn University, Auburn, AL 36849, USA
Warren D. Smith
Department of Drug Discovery and Development, Auburn University, Auburn, AL 36849, USA
Yifeng Du
Department of Drug Discovery and Development, Auburn University, Auburn, AL 36849, USA
Ryan T. Heslin
Department of Drug Discovery and Development, Auburn University, Auburn, AL 36849, USA
Sharay E. Setti
Department of Drug Discovery and Development, Auburn University, Auburn, AL 36849, USA
Jeremiah C. Pfitzer
Department of Drug Discovery and Development, Auburn University, Auburn, AL 36849, USA
Kawsar Chowdhury
Department of Drug Discovery and Development, Auburn University, Auburn, AL 36849, USA
Hao Hong
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
Subhrajit Bhattacharya
Department of Drug Discovery and Development, Auburn University, Auburn, AL 36849, USA
Muralikrishnan Dhanasekaran
Department of Drug Discovery and Development, Auburn University, Auburn, AL 36849, USA
Alexander Dityatev
Center for Neuroscience Initiative, Auburn University, Auburn, AL 36849, USA
Miranda N. Reed
Department of Drug Discovery and Development, Auburn University, Auburn, AL 36849, USA
Vishnu Suppiramaniam
Department of Drug Discovery and Development, Auburn University, Auburn, AL 36849, USA
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.
