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Ammon's Horn 2 (CA2) of the Hippocampus: A Long-Known Region with a New Potential Role in Neurodegeneration.

Accepted version
Peer-reviewed

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Type

Article

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Authors

Pang, Cindy Chi-Ching 
Kiecker, Clemens 
O'Brien, John T 
Noble, Wendy 
Chang, Raymond Chuen-Chung  ORCID logo  https://orcid.org/0000-0001-8538-7993

Abstract

The hippocampus has a critical role in cognition and human memory and is one of the most studied structures in the brain. Despite more than 400 years of research, little is known about the Ammon's horn region cornu ammonis 2 (CA2) subfield in comparison to other subfield regions (CA1, CA3, and CA4). Recent findings have shown that CA2 plays a bigger role than previously thought. Here, we review understanding of hippocampus and CA2 ontogenesis, together with basic and clinical findings about the potential role of this region in neurodegenerative disease. The CA2 has widespread anatomical connectivity, unique signaling molecules, and intrinsic electrophysiological properties. Experimental studies using in vivo models found that the CA2 region has a role in cognition, especially in social memory and object recognition. In models of epilepsy and hypoxia, the CA2 exhibits higher resilience to cell death and hypoxia in comparison with neighboring regions, and while hippocampal atrophy remains poorly understood in Parkinson's disease (PD) and dementia with Lewy bodies (DLB), findings from postmortem PD brain demonstrates clear accumulation of α-synuclein pathology in CA2, and the CA2-CA3 region shows relatively more atrophy compared with other hippocampal subfields. Taken together, there is a growing body of evidence suggesting that the CA2 can be an ideal hallmark with which to differentiate different neurodegenerative stages of PD. Here, we summarize these recent data and provide new perspectives/ideas for future investigations to unravel the contribution of the CA2 to neurodegenerative diseases.

Description

Keywords

CA2, Lewy body dementias, cognition, hippocampus, α-synuclein, Animals, Encephalitis, Hippocampus, Humans, Lewy Body Disease, Neurodegenerative Diseases, Parkinson Disease, alpha-Synuclein

Journal Title

Neuroscientist

Conference Name

Journal ISSN

1073-8584
1089-4098

Volume Title

25

Publisher

SAGE Publications
Sponsorship
Innovative and Technology Fund (ITS/381/15) of Hong Kong Special Administrative Region Government