Increased Endogenous GDNF in Mice Protects Against Age-Related Decline in Neuronal Cholinergic Markers

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Mitra , S , Turconi , G , Darreh-Shori , T , Mätlik , K , Aquilino , M , Eriksdotter , M & Andressoo , J-O 2021 , ' Increased Endogenous GDNF in Mice Protects Against Age-Related Decline in Neuronal Cholinergic Markers ' , Frontiers in aging neuroscience , vol. 13 , 714186 . https://doi.org/10.3389/fnagi.2021.714186

Title: Increased Endogenous GDNF in Mice Protects Against Age-Related Decline in Neuronal Cholinergic Markers
Author: Mitra, Sumonto; Turconi, Giorgio; Darreh-Shori, Taher; Mätlik, Kärt; Aquilino, Matilde; Eriksdotter, Maria; Andressoo, Jaan-Olle
Contributor organization: Department of Pharmacology
Helsinki Institute of Life Science HiLIFE
Faculty of Medicine
Medicum
Faculty Common Matters (Faculty of Biology and Environmental Sciences)
Date: 2021-08-12
Language: eng
Number of pages: 13
Belongs to series: Frontiers in aging neuroscience
ISSN: 1663-4365
DOI: https://doi.org/10.3389/fnagi.2021.714186
URI: http://hdl.handle.net/10138/335347
Abstract: Gradual decline in cholinergic transmission and cognitive function occurs during normal aging, whereas pathological loss of cholinergic function is a hallmark of different types of dementia, including Alzheimer's disease (AD), Lewy body dementia (LBD), and Parkinson's disease dementia (PDD). Glial cell line-derived neurotrophic factor (GDNF) is known to modulate and enhance the dopamine system. However, how endogenous GDNF influences brain cholinergic transmission has remained elusive. In this study, we explored the effect of a twofold increase in endogenous GDNF (Gdnf hypermorphic mice, Gdnf(wt/hyper)) on cholinergic markers and cognitive function upon aging. We found that Gdnf(wt/hyper) mice resisted an overall age-associated decline in the cholinergic index observed in the brain of Gdnf(wt/wt) animals. Biochemical analysis revealed that the level of nerve growth factor (NGF), which is important for survival and function of central cholinergic neurons, was significantly increased in several brain areas of old Gdnf(wt/hyper) mice. Analysis of expression of genes involved in cholinergic transmission in the cortex and striatum confirmed modulation of cholinergic pathways by GDNF upon aging. In line with these findings, Gdnf(wt/hyper) mice did not undergo an age-related decline in cognitive function in the Y-maze test, as observed in the wild type littermates. Our results identify endogenous GDNF as a potential modulator of cholinergic transmission and call for future studies on endogenous GDNF function in neurodegenerative disorders characterized by cognitive impairments, including AD, LBD, and PDD.
Subject: glial cell line-derived neurotrophic factor (GDNF)
nerve growth factor (NGF)
aging
cholinergic markers
cholinergic index
choline acetyltransferase (ChAT)
acetylcholinesterase (AChE)
brain
NERVE GROWTH-FACTOR
IMPROVES SPATIAL MEMORY
NEUROTROPHIC FACTOR
ALZHEIMERS-DISEASE
STRIATAL DOPAMINE
ACETYLCHOLINE-RELEASE
DORSOMEDIAL STRIATUM
PARKINSONS-DISEASE
NUCLEUS-ACCUMBENS
INTERNEURONS
3112 Neurosciences
3124 Neurology and psychiatry
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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