Alzheimer's disease: transiently developing dendritic changes in pyramidal cells of sector CA1 of the Ammon's horn

1997 ◽  
Vol 93 (4) ◽  
pp. 323-325 ◽  
Author(s):  
E. Braak ◽  
H. Braak
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pyramidal Cells ◽  
Ammon's Horn ◽  
Ammon’S Horn

scholarly journals Caffeine consumption during pregnancy accelerates the development of cognitive deficits in offspring in a model of tauopathy

2019 ◽  
Author(s):  
Stefania Zappettini ◽  
Emilie Faivre ◽  
Antoine Ghestem ◽  
Sébastien Carrier ◽  
Luc Buée ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Life ◽  
Pyramidal Cells ◽  
Tau Pathology ◽  
Caffeine Consumption ◽  
Early Life Exposure ◽  
Model Of Alzheimer’S Disease ◽  
Electrophysiological Recordings

AbstractPsychoactive drugs used during pregnancy can affect the development of the brain of offspring, directly triggering neurological disorders or increasing the risk for their occurrence. Caffeine is the most widely consumed psychoactive drug, including during pregnancy. In Wild type mice, early life exposure to caffeine renders offspring more susceptible to seizures. Here, we tested the long-term consequences of early life exposure to caffeine in THY-Tau22 transgenic mice, a model of Alzheimer’s disease-like Tau pathology. Caffeine exposed mutant offspring developed cognitive earlier than water treated mutants. Electrophysiological recordings of hippocampal CA1 pyramidal cells in vitro revealed that early life exposure to caffeine changed the way the glutamatergic and GABAergic drives were modified by the Tau pathology. We conclude that early-life exposure to caffeine affects the Tau phenotype and we suggest that caffeine exposure during pregnancy may constitute a risk-factor for early onset of Alzheimer’s disease-like pathology.

scholarly journals Early restoration of parvalbumin interneuron activity prevents memory loss and network hyperexcitability in a mouse model of Alzheimer’s disease

2019 ◽  
Vol 25 (12) ◽  
pp. 3380-3398 ◽  
Author(s):  
Sara Hijazi ◽  
Tim S. Heistek ◽  
Philip Scheltens ◽  
Ulf Neumann ◽  
Derya R. Shimshek ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Neuronal Network ◽  
Pyramidal Cells ◽  
Network Activity ◽  
Inhibitory Input ◽  
Model Of Alzheimer’S Disease ◽  
Entry Points ◽  
Interneuron Activity

AbstractNeuronal network dysfunction is increasingly recognized as an early symptom in Alzheimer’s disease (AD) and may provide new entry points for diagnosis and intervention. Here, we show that amyloid-beta-induced hyperexcitability of hippocampal inhibitory parvalbumin (PV) interneurons importantly contributes to neuronal network dysfunction and memory impairment in APP/PS1 mice, a mouse model of increased amyloidosis. We demonstrate that hippocampal PV interneurons become hyperexcitable at ~16 weeks of age, when no changes are observed yet in the intrinsic properties of pyramidal cells. This hyperexcitable state of PV interneurons coincides with increased inhibitory transmission onto hippocampal pyramidal neurons and deficits in spatial learning and memory. We show that treatment aimed at preventing PV interneurons from becoming hyperexcitable is sufficient to restore PV interneuron properties to wild-type levels, reduce inhibitory input onto pyramidal cells, and rescue memory deficits in APP/PS1 mice. Importantly, we demonstrate that early intervention aimed at restoring PV interneuron activity has long-term beneficial effects on memory and hippocampal network activity, and reduces amyloid plaque deposition, a hallmark of AD pathology. Taken together, these findings suggest that early treatment of PV interneuron hyperactivity might be clinically relevant in preventing memory decline and delaying AD progression.

scholarly journals Alzheimer’s disease brain-derived tau-containing extracellular vesicles: Pathobiology and GABAergic neuronal transmission

2020 ◽  
Author(s):  
Zhi Ruan ◽  
Dhruba Pathak ◽  
Srinidhi Venkatesan Kalavai ◽  
Asuka Yoshii-Kitahara ◽  
Satoshi Muraoka ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Extracellular Vesicles ◽  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Molecular Layer ◽  
Pyramidal Cells ◽  
Gabaergic Neurons ◽  
Dot Blot ◽  
Patch Clamp Recording

AbstractExtracellular vesicles (EVs) propagate tau pathology for Alzheimer’s disease (AD). How EV transmission influences AD are, nonetheless, poorly understood. To these ends, the physicochemical and molecular structure-function relationships of human brain-derived EVs, from AD and prodromal AD (pAD), were compared to non-demented controls (CTRL). AD EVs were shown to be significantly enriched in epitope-specific tau oligomers versus pAD or CTRL EVs assayed by dot-blot and atomic force microscopy tests. AD EVs were efficiently internalized by murine cortical neurons and transferred tau with higher aggregation potency than pAD and CTRL EVs. Strikingly, inoculation of tau-containing AD EVs into the outer molecular layer of the dentate gyrus induced tau propagation throughout the hippocampus. This was seen in 22 months-old C57BL/6 mice at 4.5 months post-injection by semiquantitative brain-wide immunohistochemistry tests with multiple anti-phospho-tau (p-tau) antibodies. Inoculation of the equal amount of tau from CTRL EVs or as oligomer or fibril-enriched fraction from the same AD donor showed little propagation. AD EVs induced tau accumulation in the hippocampus as oligomers or sarkosyl-insoluble proteins. Unexpectedly, p-tau cells were mostly GAD67+ GABAergic neurons and to a lesser extent, GluR2/3+ excitatory mossy cells, showing preferential EV-mediated GABAergic neuronal tau propagation. Whole-cell patch clamp recording of Cornu Ammonis (CA1) pyramidal cells showed significant reduction in the amplitude of spontaneous inhibitory post-synaptic currents. This was accompanied by reductions in c-fos+ GAD67+GABAergic neurons and GAD67+ GABAergic neuronal puncta surrounding pyramidal neurons in the CA1 region confirming reduced interneuronal projections. Our study posits a novel tau-associated pathological mechanism for brain-derived EVs.

scholarly journals Reduction of Dendritic Inhibition in CA1 Pyramidal Neurons in Amyloidosis Models of Early Alzheimer’s Disease

2020 ◽  
Vol 78 (3) ◽  
pp. 951-964
Author(s):  
Marvin Ruiter ◽  
Lotte J. Herstel ◽  
Corette J. Wierenga
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Early Stage ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Excitatory Input ◽  
Aβ Oligomers ◽  
Ca1 Pyramidal Neurons

Background: In an early stage of Alzheimer’s disease (AD), before the formation of amyloid plaques, neuronal network hyperactivity has been reported in both patients and animal models. This suggests an underlying disturbance of the balance between excitation and inhibition. Several studies have highlighted the role of somatic inhibition in early AD, while less is known about dendritic inhibition. Objective: In this study we investigated how inhibitory synaptic currents are affected by elevated Aβ levels. Methods: We performed whole-cell patch clamp recordings of CA1 pyramidal neurons in organotypic hippocampal slice cultures after treatment with Aβ-oligomers and in hippocampal brain slices from AppNL-F-G mice (APP-KI). Results: We found a reduction of spontaneous inhibitory postsynaptic currents (sIPSCs) in CA1 pyramidal neurons in organotypic slices after 24 h Aβ treatment. sIPSCs with slow rise times were reduced, suggesting a specific loss of dendritic inhibitory inputs. As miniature IPSCs and synaptic density were unaffected, these results suggest a decrease in activity-dependent transmission after Aβ treatment. We observed a similar, although weaker, reduction in sIPSCs in CA1 pyramidal neurons from APP-KI mice compared to control. When separated by sex, the strongest reduction in sIPSC frequency was found in slices from male APP-KI mice. Consistent with hyperexcitability in pyramidal cells, dendritically targeting interneurons received slightly more excitatory input. GABAergic action potentials had faster kinetics in APP-KI slices. Conclusion: Our results show that Aβ affects dendritic inhibition via impaired action potential driven release, possibly due to altered kinetics of GABAergic action potentials. Reduced dendritic inhibition may contribute to neuronal hyperactivity in early AD.

scholarly journals Nucleolar PARP-1 Expression Is Decreased in Alzheimer’s Disease: Consequences for Epigenetic Regulation of rDNA and Cognition

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Jianying Zeng ◽  
Jenny Libien ◽  
Fatima Shaik ◽  
Jason Wolk ◽  
A. Iván Hernández
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Hippocampal Pyramidal Neurons ◽  
Functional Changes ◽  
Epigenetic Regulator ◽  
Parp 1 ◽  
Sensitive Marker ◽  
Hippocampal Pyramidal Cells

Synaptic dysfunction is thought to play a major role in memory impairment in Alzheimer’s disease (AD). PARP-1 has been identified as an epigenetic regulator of plasticity and memory. Thus, we hypothesize that PARP-1 may be altered in postmortem hippocampus of individuals with AD compared to age-matched controls without neurologic disease. We found a reduced level of PARP-1 nucleolar immunohistochemical staining in hippocampal pyramidal cells in AD. Nucleolar PARP-1 staining ranged from dispersed and less intense to entirely absent in AD compared to the distinct nucleolar localization in hippocampal pyramidal neurons in controls. In cases of AD, the percentage of hippocampal pyramidal cells with nucleoli that were positive for both PARP-1 and the nucleolar marker fibrillarin was significantly lower than in controls. PARP-1 nucleolar expression emerges as a sensitive marker of functional changes in AD and suggests a novel role for PARP-1 dysregulation in AD pathology.

scholarly journals Dendritic spines are lost in clusters in Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mite Mijalkov ◽  
Giovanni Volpe ◽  
Isabel Fernaud-Espinosa ◽  
Javier DeFelipe ◽  
Joana B. Pereira ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spines ◽  
Neurodegenerative Disorder ◽  
Pyramidal Cells ◽  
Memory Deficits ◽  
Memory Storage ◽  
Excitatory Synapses ◽  
Tau Pathology ◽  
Insight Into

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a deterioration of neuronal connectivity. The pathological accumulation of tau in neurons is one of the hallmarks of AD and has been connected to the loss of dendritic spines of pyramidal cells, which are the major targets of cortical excitatory synapses and key elements in memory storage. However, the detailed mechanisms underlying the loss of dendritic spines in individuals with AD are still unclear. Here, we used graph-theory approaches to compare the distribution of dendritic spines from neurons with and without tau pathology of AD individuals. We found that the presence of tau pathology determines the loss of dendritic spines in clusters, ruling out alternative models where spine loss occurs at random locations. Since memory storage has been associated with synaptic clusters, the present results provide a new insight into the mechanisms by which tau drives synaptic damage in AD, paving the way to memory deficits through alterations of spine organization.

scholarly journals Dendritic spines are lost in clusters in patients with Alzheimer’s disease

2020 ◽  
Author(s):  
Mite Mijalkov ◽  
Giovanni Volpe ◽  
Isabel Fernaud-Espinosa ◽  
Javier DeFelipe ◽  
Joana B. Pereira ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spines ◽  
Neurodegenerative Disorder ◽  
Pyramidal Cells ◽  
Memory Deficits ◽  
Memory Storage ◽  
Excitatory Synapses ◽  
Tau Pathology ◽  
Insight Into

SUMMARYAlzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a deterioration of neuronal connectivity. The pathological accumulation of tau protein in neurons is one of the hallmarks of AD and has been connected to the loss of dendritic spines of pyramidal cells, which are the major targets of cortical excitatory synapses and key elements in memory storage. However, the detailed mechanisms underlying the loss of dendritic spines in patients with AD are still unclear. Here, comparing dendrites with and without tau pathology of AD patients, we show that the presence of tau pathology determines the loss of dendritic spines in blocks, ruling out alternative models where spine loss occurs randomly. Since memory storage has been associated with synaptic clusters, the present results provide a new insight into the mechanisms by which tau drives synaptic damage in AD, paving the way to memory deficits by altering spine organization.

scholarly journals Computer Modeling of Alzheimer’s Disease—Simulations of Synaptic Plasticity and Memory in the CA3-CA1 Hippocampal Formation Microcircuit

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1909
Author(s):  
Dariusz Świetlik ◽  
Jacek Białowąs ◽  
Janusz Moryś ◽  
Ilona Klejbor ◽  
Aida Kusiak
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Computer Modeling ◽  
Hippocampal Formation ◽  
Pyramidal Cells ◽  
Control Model ◽  
Pathological Model ◽  
Ca3 Pyramidal Cells ◽  
And Control

This paper aims to present computer modeling of synaptic plasticity and memory in the CA3-CA1 hippocampal formation microcircuit. The computer simulations showed a comparison of a pathological model in which Alzheimer’s disease (AD) was simulated by synaptic degradation in the hippocampus and control model (healthy) of CA3-CA1 networks with modification of weights for the memory. There were statistically higher spike values of both CA1 and CA3 pyramidal cells in the control model than in the pathological model (p = 0.0042 for CA1 and p = 0.0033 for CA3). A similar outcome was achieved for frequency (p = 0.0002 for CA1 and p = 0.0001 for CA3). The entropy of pyramidal cells of the healthy CA3 network seemed to be significantly higher than that of AD (p = 0.0304). We need to study a lot of physiological parameters and their combinations of the CA3-CA1 hippocampal formation microcircuit to understand AD. High statistically correlations were obtained between memory, spikes and synaptic deletion in both CA1 and CA3 cells.

Sign in / Sign up

Export Citation Format

Share Document