Alpha 7 Nicotinic Acetylcholine Receptor Expression in the Hippocampus of Patients with Schizophrenia
Date of Presentation
5-2-2024 12:00 AM
College
Rowan-Virtua School of Osteopathic Medicine
Poster Abstract
Background: Schizophrenia (SZ) is a heterogenous psychiatric condition characterized by disruptions in cognition, social activity, affect, and perception often associated with a varied combination of positive and negative symptoms. The pathophysiology behind SZ remains poorly elucidated. Earlier reports have cited the importance of the alpha 7 nicotinic acetylcholine receptors (α7nAChR) in the hippocampus and the receptor’s association with auditory sensory gating and cognitive function. Specifically, variations in the expression and functionality of α7nAChR can be linked to auditory hallucinations experienced by patients with SZ and several therapies have been researched that target α7nAChRs. However, there are very few primary research articles that directly measure α7nAChR expression in the hippocampus of patients with SZ. Earlier reports have used an indirect method of α-bungarotoxin labeling for investigating α7nAChR expression and failed to provide conclusive data. Therefore, a need was established to directly measure α7nAChR expression in the hippocampus and surrounding temporal cortex of patients with SZ.
Methods: We obtained formalin-fixed paraffin-embedded postmortem brain samples from the hippocampus and surrounding temporal cortex from subjects with SZ (n=19) and age-matched controls (n=24) from the Maryland Brain Collection and NIH NeuroBioBank. We are using an immunohistochemistry (IHC) approach, and the sections were probed with anti-α7nAChR antibodies. We have scanned the slides using an Aperio Slide Scanner at 20X (Leica BIOSYSTEMS). Next, we performed a semi-quantitative image analysis utilizing Color Deconvolution V9 tool (Aperio ImageScope, Leica BIOSYSTEMS) to develop color deconvolution heat maps for IHC images. The extent of α7nAChR immunoreactivity was compared between the SZ and age-matched control groups.
Hypothesis: The expression of α7nAChR in the hippocampus is perturbed in SZ compared to age-matched controls.
Results: A semi-quantitative analysis of the IHC data shows an increase in α7nAChR expression in the SZ samples compared to age-matched controls.
Conclusion: Our semi-quantitative data with a small sample size suggests perturbed α7nAChR expression in patients with SZ and therein, its potential role in mediating SZ-related pathophysiological and behavioral changes.
Keywords
Schizophrenia, α7nAChR, hippocampus, IHC, alpha7 Nicotinic Acetylcholine Receptor, Hallucinations, Auditory Hallucinations
Disciplines
Behavior and Behavior Mechanisms | Medical Neurobiology | Medicine and Health Sciences | Mental Disorders | Neuroscience and Neurobiology | Psychiatric and Mental Health | Psychological Phenomena and Processes
Document Type
Poster
DOI
10.31986/issn.2689-0690_rdw.stratford_research_day.160_2024
Alpha 7 Nicotinic Acetylcholine Receptor Expression in the Hippocampus of Patients with Schizophrenia
Background: Schizophrenia (SZ) is a heterogenous psychiatric condition characterized by disruptions in cognition, social activity, affect, and perception often associated with a varied combination of positive and negative symptoms. The pathophysiology behind SZ remains poorly elucidated. Earlier reports have cited the importance of the alpha 7 nicotinic acetylcholine receptors (α7nAChR) in the hippocampus and the receptor’s association with auditory sensory gating and cognitive function. Specifically, variations in the expression and functionality of α7nAChR can be linked to auditory hallucinations experienced by patients with SZ and several therapies have been researched that target α7nAChRs. However, there are very few primary research articles that directly measure α7nAChR expression in the hippocampus of patients with SZ. Earlier reports have used an indirect method of α-bungarotoxin labeling for investigating α7nAChR expression and failed to provide conclusive data. Therefore, a need was established to directly measure α7nAChR expression in the hippocampus and surrounding temporal cortex of patients with SZ.
Methods: We obtained formalin-fixed paraffin-embedded postmortem brain samples from the hippocampus and surrounding temporal cortex from subjects with SZ (n=19) and age-matched controls (n=24) from the Maryland Brain Collection and NIH NeuroBioBank. We are using an immunohistochemistry (IHC) approach, and the sections were probed with anti-α7nAChR antibodies. We have scanned the slides using an Aperio Slide Scanner at 20X (Leica BIOSYSTEMS). Next, we performed a semi-quantitative image analysis utilizing Color Deconvolution V9 tool (Aperio ImageScope, Leica BIOSYSTEMS) to develop color deconvolution heat maps for IHC images. The extent of α7nAChR immunoreactivity was compared between the SZ and age-matched control groups.
Hypothesis: The expression of α7nAChR in the hippocampus is perturbed in SZ compared to age-matched controls.
Results: A semi-quantitative analysis of the IHC data shows an increase in α7nAChR expression in the SZ samples compared to age-matched controls.
Conclusion: Our semi-quantitative data with a small sample size suggests perturbed α7nAChR expression in patients with SZ and therein, its potential role in mediating SZ-related pathophysiological and behavioral changes.