Donovan K Gálvez-Márquez, Oscar Urrego-Morales, Luis F Rodríguez-Durán, Federico Bermudez-Rattoni
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引用次数: 0
Abstract
Rationale: One of the earliest changes associated with Alzheimer's disease (AD) is the loss of catecholaminergic terminals in the cortex and hippocampus originating from the Locus Coeruleus (LC). This decline leads to reduced catecholaminergic neurotransmitters in the hippocampus, affecting synaptic plasticity and spatial memory. However, it is unclear whether restoring catecholaminergic transmission in the terminals from the LC may alleviate the spatial memory deficits associated with AD.
Objectives: This study aims to investigate the effects of optogenetic stimulation of LC catecholaminergic projections on alleviating spatial memory and synaptic plasticity deficits associated with AD.
Methods: We conducted experiments using a 12-month-old 3xTgAD mouse model (AD-TH) that expresses Cre recombinase under the control of the tyrosine hydroxylase (TH) gene. This model enabled us to photostimulate the terminals from the LC in the hippocampal CA1 region before performing two different spatial memory tasks and inducing long-term plasticity.
Results: Optogenetic stimulation successfully reversed the impairment of spatial memory retrieval in aging AD-TH mice. Furthermore, this stimulation restored levels of catecholaminergic neurotransmitters in the hippocampus and enhanced synaptic plasticity, as demonstrated by a long-term potentiation (LTP) protocol.
Conclusions: These findings suggest a critical role for the LC-hippocampal CA1 catecholaminergic circuitry in disrupting synaptic plasticity and the spatial memory deficits characteristic of the early stages of AD. The study highlights the potential for targeting LC catecholaminergic pathways as a therapeutic strategy to improve cognitive deficits experienced by AD patients.
期刊介绍：
Official Journal of the European Behavioural Pharmacology Society (EBPS)
Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields:
Human Psychopharmacology: Experimental
This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered.
Human Psychopharmacology: Clinical and Translational
This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects.
Preclinical psychopharmacology: Behavioral and Neural
This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels.
Preclinical Psychopharmacology: Translational
This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways.
Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic
This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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