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NLX-101, a 5-HT1A receptor-biased agonist, improves pattern separation and stimulates neuroplasticity in aged rats
- Source :
- Neurobiology of Aging, 124, 52-59. Elsevier Science
- Publication Year :
- 2023
- Publisher :
- Elsevier Science, 2023.
-
Abstract
- 5-HT1A serotonin receptors may play a role in cognitive function changes related to advanced age. Here, we investigated the effects of acute and repeated treatment with NLX-101 (F15599), a postsynaptic 5-HT1A receptor-biased agonist, and F13714, a presynaptic 5-HT1A receptor-biased agonist on spatial object pattern separation (OPS) in aged (22-24 months) rats. Neuroplasticity markers including brain-derived neurotrophic factor, PSD95, synaptophysin, and doublecortin were evaluated in the hippocampus. Un-like younger rats, aged rats were incapable of discriminating any new position of the objects in the arena, reflecting the detrimental effect of aging on pattern separation. However, aged animals treated with NLX-101 showed a significant cognitive improvement in the OPS test, accompanied by increases in hippocampal brain-derived neurotrophic factor and PSD95 protein levels. In contrast, no improvement in OPS performance was observed when aged rats received F13714. Both F13714 and NLX-101 increased the number of newborn neurons in the hippocampi of aged rats. These findings provide a rationale for targeting post-synaptic 5-HT1A as a treatment for cognitive deficits related to aging.(c) 2023 Elsevier Inc. All rights reserved.
- Subjects :
- Aging
F15599
NLX-101
PROTEINS
General Neuroscience
ADULT NEUROGENESIS
F13714
5-HT 1A receptor
HIPPOCAMPAL NEUROGENESIS
DENTATE GYRUS
Pattern separation
SYNAPTIC PLASTICITY
DEFICITS
COGNITION
Neuroplasticity
Neurology (clinical)
Geriatrics and Gerontology
BRAIN
Aged rats
Developmental Biology
NEUROTROPHIC FACTOR
Subjects
Details
- Language :
- English
- ISSN :
- 15581497 and 01974580
- Volume :
- 124
- Database :
- OpenAIRE
- Journal :
- Neurobiology of Aging
- Accession number :
- edsair.doi.dedup.....d328c83a30e0436872e2ab14b36749a5