Increased hippocampal CA1 density of serotonergic terminals in a triple transgenic mouse model of Alzheimer's disease: an ultrastructural study

Noristani, Harun N.; Meadows, Roger S.; Olabarria, Markel; Verkhratsky, Alexei; Rodrı́guez, José J.

doi:10.1038/cddis.2011.79

Cited by 36 publications

(27 citation statements)

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“…Furthermore, platelet microparticles promote macrophage differentiation of monocytes [22], which is opposite to our observations. The mechanism by which contact with the endothelium results in the differentiation of blood monocytes into endothelial-like cells remains to be determined.…”

Section: Discussioncontrasting

confidence: 99%

Phenotypic and Functional Changes in Blood Monocytes Following Adherence to Endothelium

2012

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ObjectiveBlood monocytes are known to express endothelial-like genes during co-culture with endothelium. In this study, the time-dependent change in the phenotype pattern of primary blood monocytes after adhering to endothelium is reported using a novel HLA-A2 mistyped co-culture model.Methods and ResultsFreshly isolated human PBMCs were co-cultured with human umbilical vein endothelial cells or human coronary arterial endothelial cells of converse human leukocyte antigen A2 (HLA-A2) status. This allows the tracking of the PBMC-derived cells by HLA-A2 expression and assessment of their phenotype pattern over time. PBMCs that adhered to the endothelium at the start of the co-culture were predominantly CD11b+ blood monocytes. After 24 to 72 hours in co-culture, the endothelium-adherent monocytes acquired endothelial-like properties including the expression of endothelial nitric oxide synthase, CD105, CD144 and vascular endothelial growth factor receptor 2. The expression of monocyte/macrophage lineage antigens CD14, CD11b and CD36 were down regulated concomitantly. The adherent monocytes did not express CD115 after 1 day of co-culture. By day 6, the monocyte-derived cells expressed vascular cell adhesion molecule 1 in response to tumour necrosis factor alpha. Up to 10% of the PBMCs adhered to the endothelium. These monocyte-derived cells contributed up to 30% of the co-cultured cell layer and this was dose-dependent on the PBMC seeding density.ConclusionsHuman blood monocytes undergo rapid phenotype change to resemble endothelial cells after adhering to endothelium.

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Section: Discussioncontrasting

confidence: 99%

Phenotypic and Functional Changes in Blood Monocytes Following Adherence to Endothelium

2012

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“…In fact, there is no significant neuronal loss in memory-associated areas, such as the EC and HC, in the 3xTg-AD animal model (Oddo et al, 2003a(Oddo et al, , 2003bRohn et al, 2008;Bittner et al, 2010). Nonetheless, loss of synapses and/or dendritic spines as well as compromised long-term potentiation have been detected in several brain regions, suggesting impaired synaptic connectivity and functions in this animal model (Oddo et al, 2003a;Bertoni-Freddari et al, 2008;Bittner et al, 2010;Noristani et al, 2011). Therefore the astrocytic atrophy in the EC may underlie synaptic pathology being the basis of cognitive and memory impairment at the early stages of the AD.…”

Section: Discussionmentioning

confidence: 81%

P1‐178: Early astrocytic atrophy in the Entorhinal cortex of a triple transgenic animal model of Alzheimer's disease

Yeh

Olabarria

Noristani

et al. 2010

Alzheimer's & Dementia

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The EC (entorhinal cortex) is fundamental for cognitive and mnesic functions. Thus damage to this area appears as a key element in the progression of AD (Alzheimer's disease), resulting in memory deficits arising from neuronal and synaptic alterations as well as glial malfunction. In this paper, we have performed an in-depth analysis of astroglial morphology in the EC by measuring the surface and volume of the GFAP (glial fibrillary acidic protein) profiles in a triple transgenic mouse model of AD [3xTg-AD (triple transgenic mice of AD)]. We found significant reduction in both the surface and volume of GFAP-labelled profiles in 3xTg-AD animals from very early ages (1 month) when compared with non-Tg (non-transgenic) controls (48 and 54%, reduction respectively), which was sustained for up to 12 months (33 and 45% reduction respectively). The appearance of Ab (amyloid b-peptide) depositions at 12 months of age did not trigger astroglial hypertrophy; nor did it result in the close association of astrocytes with senile plaques. Our results suggest that the AD progressive cognitive deterioration can be associated with an early reduction of astrocytic arborization and shrinkage of the astroglial domain, which may affect synaptic connectivity within the EC and between the EC and other brain regions. In addition, the EC seems to be particularly vulnerable to AD pathology because of the absence of evident astrogliosis in response to Ab accumulation. Thus we can consider that targeting astroglial atrophy may represent a therapeutic strategy which might slow down the progression of AD.

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“…Decreased 5-HT activity is associated with menopause (Halbreich et al, 1995), as well as cognitive and mood disorders (Sun et al, 2004; Garcia-Alloza et al, 2005; You et al, 2005; Mowla et al, 2007; Noristani et al, 2011; Waider et al, 2011). The beneficial cognitive and mood effects of estrogen-containing HT and agents that enhance serotonergic neurotransmission, such as selective serotonin reuptake inhibitors (SSRI), have been demonstrated (Campbell and Whitehead, 1977; Best et al, 1992; Ohkura et al, 1995; Arpels, 1996; Gregoire et al, 1996; Gleason et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Benefits of Hormone Therapy Estrogens Depend on Estrogen Type: 17β-Estradiol and Conjugated Equine Estrogens Have Differential Effects on Cognitive, Anxiety-Like, and Depressive-Like Behaviors and Increase Tryptophan Hydroxylase-2 mRNA Levels in Dorsal Raphe Nucleus Subregions

et al. 2016

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Decreased serotonin (5-HT) function is associated with numerous cognitive and affective disorders. Women are more vulnerable to these disorders and have a lower rate of 5-HT synthesis than men. Serotonergic neurons in the dorsal raphe nucleus (DRN) are a major source of 5-HT in the forebrain and play a critical role in regulation of stress-related disorders. In particular, polymorphisms of tryptophan hydroxylase-2 (TpH2, the brain-specific, rate-limiting enzyme for 5-HT biosynthesis) are implicated in cognitive and affective disorders. Administration of 17β-estradiol (E2), the most potent naturally circulating estrogen in women and rats, can have beneficial effects on cognitive, anxiety-like, and depressive-like behaviors. Moreover, E2 increases TpH2 mRNA in specific subregions of the DRN. Although conjugated equine estrogens (CEE) are a commonly prescribed estrogen component of hormone therapy in menopausal women, there is a marked gap in knowledge regarding how CEE affects these behaviors and the brain 5-HT system. Therefore, we compared the effects of CEE and E2 treatments on behavior and TpH2 mRNA. Female Sprague-Dawley rats were ovariectomized, administered either vehicle, CEE, or E2 and tested on a battery of cognitive, anxiety-like, and depressive-like behaviors. The brains of these animals were subsequently analyzed for TpH2 mRNA. Both CEE and E2 exerted beneficial behavioral effects, although efficacy depended on the distinct behavior and for cognition, on the task difficulty. Compared to CEE, E2 generally had more robust anxiolytic and antidepressant effects. E2 increased TpH2 mRNA in the caudal and mid DRN, corroborating previous findings. However, CEE increased TpH2 mRNA in the caudal and rostral, but not the mid, DRN, suggesting that distinct estrogens can have subregion-specific effects on TpH2 gene expression. We also found differential correlations between the level of TpH2 mRNA in specific DRN subregions and behavior, depending on the type of behavior. These distinct associations imply that cognition, anxiety-like, and depressive-like behaviors are modulated by unique serotonergic neurocircuitry, opening the possibility of novel avenues of targeted treatment for different types of cognitive and affective disorders.

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Increased hippocampal CA1 density of serotonergic terminals in a triple transgenic mouse model of Alzheimer's disease: an ultrastructural study

Cited by 36 publications

References 50 publications

Phenotypic and Functional Changes in Blood Monocytes Following Adherence to Endothelium

Phenotypic and Functional Changes in Blood Monocytes Following Adherence to Endothelium

P1‐178: Early astrocytic atrophy in the Entorhinal cortex of a triple transgenic animal model of Alzheimer's disease

Benefits of Hormone Therapy Estrogens Depend on Estrogen Type: 17β-Estradiol and Conjugated Equine Estrogens Have Differential Effects on Cognitive, Anxiety-Like, and Depressive-Like Behaviors and Increase Tryptophan Hydroxylase-2 mRNA Levels in Dorsal Raphe Nucleus Subregions

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