Cognitive Decline in Neuronal Aging and Alzheimer's Disease: Role of NMDA Receptors and Associated Proteins

Ávila, Jesús; Llorens‐Martin, María; Pallas‐Bazarra, Noemí; Bolós, Marta; Perea, Juan Ramón; Rodríguez-Matellán, Alberto; Hernández, Félix

doi:10.3389/fnins.2017.00626

Cited by 50 publications

(32 citation statements)

References 108 publications

(124 reference statements)

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“…Dendritic spines are regulated by several factors, including neurotransmitters, hormones, and neurotrophins (for review see Flores, Morales‐Medina, et al, ; Yasuda, ). Two neurotrophins are critical for the maintenance of dendritic spines, BDNF and NGF (for review see Arevalo, Azcoitia, Gonzalez‐Burgos, & Garcia‐Segura, ; Avila et al, ), which are produced by the placenta (for review see Dhoable, ; Sahay et al, , ). Furthermore, it is well known that both BDNF and NGF reduce their levels with aging.…”

Section: Discussionmentioning

confidence: 99%

“…Several reports suggest that dendritic spines are independent structures (for review see Avila et al, ), however, changes in the number of dendritic spines also cause changes in the dendritic tree, as a compensating or plastic mechanism. It is possible to assume that due to the increase in the number of dendritic spines, the dendrite rearrangement its length/arborization to keep the communication system in equilibrium in the old animals.…”

Section: Discussionmentioning

confidence: 99%

“…A recent report for our group demonstrated that GH induced an increase in dendritic length in layer 3 of the PFC and CA1 of the dorsal hippocampus (Olivarez‐Hernández et al, ). In addition, cognitive functions decline during aging and several reports have demonstrated an increase in the extracellular levels of glutamate, that in high levels may induce neurotoxicity (Brewer, ; Choi et al, ; Zoia et al, ) and also alter mitochondrial function (Avila et al, ; Choi et al, ; Plaitakis, Zaganas, & Spanaki, ), which results in reduced dendritic length (Jia et al, ). In addition, reduced glutamatergic input to layer 5 of the PFC also reduced dendritic length of the pyramidal neurons (Kelly, Huang, Meltzer, & Martina, ).…”

Section: Discussionmentioning

confidence: 99%

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Pregnancies alters spine number in cortical and subcortical limbic brain regions of old rats

Flores-Vivaldo

Camacho-Ábrego

Picazo

et al. 2019

Synapse

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Pregnancy is a complex process, involving a number of hormones and trophic factors, many of which are formed in the placenta. Several of these trophic factors have an effect at the neuronal level, such as BDNF. Consequently, recent reports have shown that exposure to these hormones (estrogen and progesterone) and trophic factors such as BDNF exert a neuroprotective effect. Here, we study the effect of the number of pregnancies on dendritic morphology of aged female rats (18 months of age). Rats of the 18‐month‐old Sprague Dawley strain with zero, one, two, and three gestations were evaluated for locomotor activity, and Golgi–Cox stain was performed to evaluate the dendritic morphology parameters, the number of dendritic spines, total dendritic length, and branching order number. Adult nulliparous rats (3 months of age) were used as another control group. Adult nulliparous and aging rats with two pregnancies showed an increase in locomotor activity. Adult nulliparous showed an increase in the dendritic spine number compared to old nulliparous rats in both layers of the PFC, the DG, and NAcc. Old rats with two and three pregnancies also showed an increase in the number of dendritic spines compared to old nulliparous rats in layers 3 and 5 of the PFC and in the CA1. Aging animals with one pregnancy also showed an increase in dendritic length compared to old nulliparous rats in the CA1. Our results clearly suggest that two and three pregnancies increase the dendritic spines number in the PFC and CA1 of aged female rats.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Pregnancies alters spine number in cortical and subcortical limbic brain regions of old rats

Flores-Vivaldo

Camacho-Ábrego

Picazo

et al. 2019

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“…This implies a major role of the clock molecular machinery in shaping neuronal communication and synaptic plasticity, which is also supported by circadian studies of cellular correlates of synaptic plasticity (Chaudhury et al., ; Ikeda et al., ). Importantly, such a role may also support clock‐regulated transcriptional control in neurodevelopment, in aging, as well as in neuropsychiatric and neurological diseases, because of the established functions of synaptic components in these aspects (Akaneya et al., ; Avila et al., ; Südhof, ).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional control of synaptic components by the clock machinery

Hannou

Roy

Roig

et al. 2019

Eur J of Neuroscience

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Circadian rhythms are generated in mammals by a central clock located in the suprachiasmatic nucleus of the hypothalamus, which regulates the homeostasis of many biological processes. At the molecular level, the regulation of circadian rhythms is under the control of transcriptional‐translational feedback loops composed of clock factors, including transcription factors. In the brain, synaptic plasticity has been shown to vary with a 24‐h rhythm. Also, when measured at a given time‐of‐day, synaptic plasticity has been observed to be disrupted by dysregulation of clock factors. This could suggest a regulation of synaptic functions by the clock machinery. Interestingly, many studies provide support for direct and indirect transcriptional regulation by core clock factors, including rhythmic gene expression, for a variety of synaptic components. Indeed, the gene of several neuropeptides, neurotransmitter regulators, receptors and transporters, ion channels, vesicle proteins, and adhesion and scaffolding molecules present evidence to be clock‐controlled. We here present, while considering different regions of the mammalian brain, an overview of the extent of the transcriptional control of synaptic components by the clock machinery.

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“…The "late-onset" accumulation of amyloid-beta also raises the question of how "age" is translated in terms of cellular/tissue environment, leading to the increase in amyloid-beta accumulation. Existing interrelating theories and interpretations include (i) increased inflammation [75][76][77], (ii) increased oxidative stress [78][79][80], (iii) mitochondrial dysfunction [81], (iv) calcium homeostasis defect [82], (v) accumulation of mutations [83], (vi) stem cell fatigue and depletion [84], (vii) decreased proper brain-immune crosstalk [85], (viii) brain blood barrier dysfunction [86], (ix) decreased amyloid-beta clearance [87], (x) increased amyloid-beta deposition [88], and (xi) synaptic senescence [89,90]. In his book The end of Alzheimer's (2017) [91], Dale Bredesen listed 36 facilitators, which can be roughly categorized as inflammation, lack of nutrition and/or hormone, and toxins.…”

Section: Late-onset Accumulation Of Amyloid-beta In Sgo1 Brainmentioning

confidence: 99%

Critical role of mitosis in spontaneous late-onset Alzheimer’s disease; from a Shugoshin 1 cohesinopathy mouse model

et al. 2018

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From early-onset Alzheimer's disease (EOAD) studies, the amyloid-beta hypothesis emerged as the foremost theory of the pathological causes of AD. However, how amyloid-beta accumulation is triggered and progresses toward senile plaques in spontaneous late-onset Alzheimer's disease (LOAD) in humans remains unanswered. Various LOAD facilitators have been proposed, and LOAD is currently considered a complex disease with multiple causes. Mice do not normally develop LOAD. Possibly due to the multiple causes, proposed LOAD facilitators have not been able to replicate spontaneous LOAD in mice, representing a disease modeling issue. Recently, we reported spontaneous late-onset development of amyloid-beta accumulation in brains of Shugoshin 1 (Sgo1) haploinsufficient mice, a cohesinopathy-mediated chromosome instability model. The result for the first time expands disease relevance of mitosis studies to a major disease other than cancers. Reverse-engineering of the model would shed light on the process of late-onset amyloid-beta accumulation in the brain and spontaneous LOAD development, and contribute to development of interventions for LOAD. This review will discuss the Sgo1 model, our current "three-hit hypothesis" regarding LOAD development with an emphasis on critical role of prolonged mitosis in amyloid-beta accumulation, and implications for human LOAD intervention and treatment. Abbreviations: Alzheimer's disease (AD); Late-onset Alzheimer's disease (LOAD); Early-onset Alzheimer's disease (EOAD); Shugoshin-1 (Sgo1); Chromosome Instability (CIN); apolipoprotein (Apoe); Central nervous system (CNS); Amyloid precursor protein (APP); N-methyl-d-aspartate (NMDA); Hazard ratio (HR); Cyclin-dependent kinase (CDK); Chronic Atrial Intestinal Dysrhythmia (CAID); beta-secretase 1 (BACE); phosphor-Histone H3 (p-H3); Research and development (R&D); Non-steroidal anti-inflammatory drugs (NSAIDs); Brain blood barrier (BBB).

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Cognitive Decline in Neuronal Aging and Alzheimer's Disease: Role of NMDA Receptors and Associated Proteins

Cited by 50 publications

References 108 publications

Pregnancies alters spine number in cortical and subcortical limbic brain regions of old rats

Pregnancies alters spine number in cortical and subcortical limbic brain regions of old rats

Transcriptional control of synaptic components by the clock machinery

Critical role of mitosis in spontaneous late-onset Alzheimer’s disease; from a Shugoshin 1 cohesinopathy mouse model

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