Parvalbumin Loss Following Chronic Sub-Anesthetic NMDA Antagonist Treatment is Age-Dependent in the Hippocampus: Implications for Modeling NMDA Hypofunction.
Jennifer A. Honeycutt, James J Chrobak
Neuroscience November 21, 2018 DOI: 10.1016/j.neuroscience.2018.09.031 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rats (1-month-old and adult) treated chronically with ketamine |
| Intervention | Ketamine |
| Duration | 14 days of sub-anesthetic ketamine treatment |
| Topics | Ketamine |
| Keywords | Nmda hypofunction Development Hippocampus Parvalbumin Schizophrenia |
| Key findings | Age, but not the timing of tissue collection after treatment, affected hippocampal parvalbumin cell counts following 14 days of sub-anesthetic ketamine. One-month-old rats showed a significant ketamine-induced decrease in hippocampal PV, whereas adult rats showed a modest increase. The authors propose that PV is a dynamic marker and that PV changes after NMDA antagonist treatment should be interpreted in the context of age. |
Abstract
A marked decrease in parvalbumin (PV), a calcium-binding protein specific to a subset of GABAergic neurons, is a consistent finding in postmortem schizophrenic brain tissue. This reduction is selective to PV and is regionally specific, occurring primarily in the prefrontal cortex and hippocampus (HPC) of patients. Rodent models of NMDA receptor hypofunction utilizing NMDA antagonist treatments - e.g. ketamine (KET) - show schizophrenia-like cognitive and behavioral impairments with parallel changes in PV. While decreased PV is considered a hallmark of neuropathology in schizophrenia, previous work elucidating the effects of KET administration on PV are contradictory, with findings suggesting decreased, increased, or no change in PV expression. Upon close examination of the procedures used across studies, there are two primary inconsistencies, including: (1) the age of animals used; and (2) the timeline of post-treatment tissue collection. To better understand whether these key differences impact observed PV changes, the present study investigated the impact of age and time of sacrifice on chronic KET-induced PV changes in the neocortex and HPC. Our findings suggest an effect of age, but not sacrifice timeline, on PV cell count following 14 days of sub-anesthetic KET treatment. We provide evidence that 1-month-old rats exhibit a significant KET-induced HPC PV decrease, while adult rats show a modest increase in HPC PV following chronic KET. Taken together, we propose that PV is a dynamic marker, and that changes in cell counts - and their interpretation - following NDMA antagonist treatment should be considered in the context of age.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 4
- A review of potential neuropathological changes associated with ketamine Expert Opinion on Drug Safety May 3, 2022
- Multi-level therapeutic actions of cannabidiol in ketamine-induced schizophrenia psychopathology in male rats. Neuropsychopharmacology December 1, 2024
- NMDA receptor antagonist induced c-Fos expression in the medial entorhinal cortex during postnatal development. Frontiers in Neural Circuits 2025
- The positive allosteric modulator of the mGlu2 receptor JNJ-46356479 partially improves neuropathological deficits and schizophrenia-like behaviors in a postnatal ketamine mice model. Journal of Psychiatric Research April 26, 2020
Cites 8
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- Ketamine – More mechanisms of action than just NMDA blockade Trends in Anaesthesia and Critical Care March 22, 2014
- Is the Acute NMDA Receptor Hypofunction a Valid Model of Schizophrenia? Schizophrenia Bulletin September 28, 2011
- New Hippocampal Neurons Mature Rapidly in Response to Ketamine But Are Not Required for Its Acute Antidepressant Effects on Neophagia in Rats eNeuro March 1, 2016
- Imaging patients with psychosis and a mouse model establishes a spreading pattern of hippocampal dysfunction and implicates glutamate as a pathogenic driver Neuron April 10, 2013
and 3 more in the library