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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Sex differences in brain metabolism and their relationship to neurodegenerative diseases like Alzheimer’s are an important emerging topic in neuroscience. Intrinsic anatomic and metabolic differences related to male and female physiology have been described, underscoring the importance of considering biological sex in studying brain metabolism and associated pathologies. The hippocampus is a key structure exhibiting sex differences in volume and connectivity. Adult neurogenesis in the dentate gyrus, dendritic spine density, and electrophysiological plasticity contribute to the hippocampus’ remarkable plasticity. Glucose transporters GLUT3 and GLUT4 are expressed in human hippocampal neurons, with proper glucose metabolism being crucial for learning and memory. Sex hormones play a major role, with the aromatase enzyme that generates estradiol increasing in neurons and astrocytes as an endogenous neuroprotective mechanism. Inhibition of aromatase increases gliosis and neurodegeneration after brain injury. Genetic variants of aromatase may confer higher Alzheimer’s risk. Estrogen replacement therapy in postmenopausal women prevents hippocampal hypometabolism and preserves memory. Insulin is also a key regulator of hippocampal glucose metabolism and cognitive processes. Dysregulation of the insulin-sensitive glucose transporter GLUT4 may explain the comorbidity between type II diabetes and Alzheimer’s. GLUT4 colocalizes with the insulin-regulated aminopeptidase IRAP in neuronal vesicles, suggesting an activity-dependent glucose uptake mechanism. Sex differences in brain metabolism are an important factor in understanding neurodegenerative diseases, and future research must elucidate the underlying mechanisms and potential therapeutic implications of these differences.

Details

Title
Sexual and Metabolic Differences in Hippocampal Evolution: Alzheimer’s Disease Implications
Author
Martínez-Martos, José Manuel 1   VIAFID ORCID Logo  ; Cantón-Habas, Vanesa 2   VIAFID ORCID Logo  ; Rich-Ruíz, Manuel 2   VIAFID ORCID Logo  ; Reyes-Medina, María José 3   VIAFID ORCID Logo  ; María Jesús Ramírez-Expósito 1   VIAFID ORCID Logo  ; María del Pilar Carrera-González 4   VIAFID ORCID Logo 

 Experimental and Clinical Physiopathology Research Group CTS-1039, Department of Health Sciences, Faculty of Health Sciences, University of Jaen, Las Lagunillas University Campus, 23009 Jaen, Spain; [email protected] (J.M.M.-M.); [email protected] (M.J.R.-E.) 
 Department of Nursing, Pharmacology and Physiotherapy, Faculty of Medicine and Nursing, University of Córdoba, 14004 Córdoba, Spain; [email protected] (V.C.-H.); [email protected] (M.R.-R.); [email protected] (M.J.R.-M.); Maimonides Institute of Biomedical Research of Córdoba (IMIBIC) IMIBIC Building, Reina Sofia University Hospital, Av. Menéndez Pidal, s/n, 14004 Cordoba, Spain 
 Department of Nursing, Pharmacology and Physiotherapy, Faculty of Medicine and Nursing, University of Córdoba, 14004 Córdoba, Spain; [email protected] (V.C.-H.); [email protected] (M.R.-R.); [email protected] (M.J.R.-M.) 
 Experimental and Clinical Physiopathology Research Group CTS-1039, Department of Health Sciences, Faculty of Health Sciences, University of Jaen, Las Lagunillas University Campus, 23009 Jaen, Spain; [email protected] (J.M.M.-M.); [email protected] (M.J.R.-E.); Maimonides Institute of Biomedical Research of Córdoba (IMIBIC) IMIBIC Building, Reina Sofia University Hospital, Av. Menéndez Pidal, s/n, 14004 Cordoba, Spain 
First page
1547
Publication year
2024
Publication date
2024
Publisher
MDPI AG
e-ISSN
20751729
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3149697610
Copyright
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.