TSPO and amyloid deposits in sub-regions of the hippocampus in the 3xTgAD mouse model of Alzheimer’s disease

Tournier, Benjamin B.; Tsartsalis, Stergios; Rigaud, Daphney; Fossey, Christine; Cailly, Thomas; Fabis, Frédéric; Pham, Tien; Grégoire, Marie‐Claude; Kovari, Eniko Veronika; Moulin-Sallanon, Marcelle; Savioz, Armand; Millet, Philippe

doi:10.1016/j.nbd.2018.09.022

Cited by 46 publications

(44 citation statements)

References 80 publications

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“…As for morphological and biochemical correlates, the cholinergic lesion increased hippocampal astrogliosis in agreement with similar findings in cholinergically depleted adult rats [107,124] and aged mice [56], as well as in AD patients [125]. In the present study, we did not find any effect of the immunotoxic cholinergic lesion on hippocampal neurogenesis, in line with previous research in adult [126] and aged [56] mice.…”

Section: Discussionsupporting

confidence: 93%

“…Considering the fact that in mice adult neurogenesis is predominant in the dorsal hippocampus respect to the ventral hippocampus [101][102][103][104] and that the neurodegenerative AD-like syndrome affects at a first stage the dorsal hippocampus and the dorsal hippocampusdependent spatial learning and memory functions [105][106][107], we decided to analyze volume, neurogenesis, and astrogliosis parameters in the dorsal horn of the hippocampus.…”

Section: Morphological Analysesmentioning

confidence: 99%

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Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice

et al. 2020

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Background In recent years, mechanistic, epidemiologic, and interventional studies have indicated beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) against brain aging and age-related cognitive decline, with the most consistent effects against Alzheimer’s disease (AD) confined especially in the early or prodromal stages of the pathology. In the present study, we investigated the action of n-3 PUFA supplementation on behavioral performances and hippocampal neurogenesis, volume, and astrogliosis in aged mice subjected to a selective depletion of basal forebrain cholinergic neurons. Such a lesion represents a valuable model to mimic one of the most reliable hallmarks of early AD neuropathology. Methods Aged mice first underwent mu-p75-saporin immunotoxin intraventricular lesions to obtain a massive cholinergic depletion and then were orally supplemented with n-3 PUFA or olive oil (as isocaloric control) for 8 weeks. Four weeks after the beginning of the dietary supplementation, anxiety levels as well as mnesic, social, and depressive-like behaviors were evaluated. Subsequently, hippocampal morphological and biochemical analyses and n-3 PUFA brain quantification were carried out. Results The n-3 PUFA treatment regulated the anxiety alterations and reverted the novelty recognition memory impairment induced by the cholinergic depletion in aged mice. Moreover, n-3 PUFA preserved hippocampal volume, enhanced neurogenesis in the dentate gyrus, and reduced astrogliosis in the hippocampus. Brain levels of n-3 PUFA were positively related to mnesic abilities. Conclusions The demonstration that n-3 PUFA are able to counteract behavioral deficits and hippocampal neurodegeneration in cholinergically depleted aged mice promotes their use as a low-cost, safe nutraceutical tool to improve life quality at old age, even in the presence of first stages of AD.

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Section: Discussionsupporting

confidence: 93%

Section: Morphological Analysesmentioning

confidence: 99%

Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice

et al. 2020

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“…DH appears to be primarily responsible for the cognitive functions of the hippocampus (Moser & Moser, 1998;Sahay & Hen, 2007;Barkus et al, 2010;Fanselow & Dong, 2010), which is consistent with our finding that that genes associated with learning and memory were only impacted in DH. Our findings also add to evidence suggesting that DH is more vulnerable to neuroinflammation and other pathology than VH (Fuster-Matanzo et al, 2011;Stouffer et al, 2015;Dobryakova et al, 2017;Dobryakova et al, 2019;Tournier et al, 2019).…”

Section: Discussionsupporting

confidence: 76%

A Multi-Gene Synaptic Plasticity Array Identifies Candidate Molecular Underpinnings of Cognitive and Mood Deficits in Rats with Heart Failure

et al. 2020

Preprint

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Chronic heart failure (HF) is a serious disorder that afflicts more than 26 million patients worldwide. HF is comorbid with depression, anxiety and memory deficits that have serious implications for quality of life and self-care in patients who have HF. Despite evidence that cognitive performance is worse in HF patients with reduced ejection fraction than in HF patients with preserved cardiac function, there are few studies that have assessed the effects of severely reduced ejection fraction (≤40%) on cognition in non-human animal models. Moreover, very limited information is available regarding the effects of HF on genetic markers of synaptic plasticity in brain areas critical for memory and mood regulation. We induced HF in male rats and tested mood and anxiety (sucrose preference and elevated plus maze) and memory (spontaneous alternation and inhibitory avoidance) and measured the simultaneous expression of 84 synaptic plasticity-associated genes in dorsal (DH) and ventral hippocampus (VH), basolateral (BLA) and central amygdala (CeA,) and prefrontal cortex (PFC). We also included the hypothalamic paraventricular nucleus (PVN), which has been implicated in neurohumoral activation in HF. Our results show that rats with severely reduced ejection fraction displayed signs of polydipsia, anhedonia, increased anxiety, and impaired memory in both tasks. HF also produced a drastic downregulation of synaptic-plasticity genes in PFC and PVN, moderate decreases in DH and CeA and minimal effects in BLA and VH. Collectively, these findings identify candidate brain areas and molecular mechanisms underlying HF-induced disturbances in mood and memory.

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“…A major brain cell type that displays TSPO upregulation in neuroinflammation is microglia [122,136,137,138,139,140,141]. Given microglia adapt to a variety of challenges across their lifespan, it is not surprising that they are a heterogeneous population consisting of multiple phenotypes [142].…”

Section: Cellular and Functional Interpretation Of Tspo Pet Signalsmentioning

confidence: 99%

Recent Developments in TSPO PET Imaging as A Biomarker of Neuroinflammation in Neurodegenerative Disorders

Werry

Bright

Piguet

et al. 2019

IJMS

202

159

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Neuroinflammation is an inflammatory response in the brain and spinal cord, which can involve the activation of microglia and astrocytes. It is a common feature of many central nervous system disorders, including a range of neurodegenerative disorders. An overlap between activated microglia, pro-inflammatory cytokines and translocator protein (TSPO) ligand binding was shown in early animal studies of neurodegeneration. These findings have been translated in clinical studies, where increases in TSPO positron emission tomography (PET) signal occur in disease-relevant areas across a broad spectrum of neurodegenerative diseases. While this supports the use of TSPO PET as a biomarker to monitor response in clinical trials of novel neurodegenerative therapeutics, the clinical utility of current TSPO PET radioligands has been hampered by the lack of high affinity binding to a prevalent form of polymorphic TSPO (A147T) compared to wild type TSPO. This review details recent developments in exploration of ligand-sensitivity to A147T TSPO that have yielded ligands with improved clinical utility. In addition to developing a non-discriminating TSPO ligand, the final frontier of TSPO biomarker research requires developing an understanding of the cellular and functional interpretation of the TSPO PET signal. Recent insights resulting from single cell analysis of microglial phenotypes are reviewed.

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TSPO and amyloid deposits in sub-regions of the hippocampus in the 3xTgAD mouse model of Alzheimer’s disease

Cited by 46 publications

References 80 publications

Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice

Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice

A Multi-Gene Synaptic Plasticity Array Identifies Candidate Molecular Underpinnings of Cognitive and Mood Deficits in Rats with Heart Failure

Recent Developments in TSPO PET Imaging as A Biomarker of Neuroinflammation in Neurodegenerative Disorders

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