scholarly journals Effects of Memantine on the Spontaneous Firing Frequency of CA1 Pyramidal Neurons in Intact and Alzheimer's Rats Model: An Electrophysiological Study

2021 ◽  
Author(s):  
Nastaran Zamani ◽  
◽  
Ahmad Ali Moazedi ◽  
Mohamad Reza Afarinesh ◽  
Mehdi Pourmehdi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pyramidal Neurons ◽  
Saline Group ◽  
Firing Frequency ◽  
Male Rats ◽  
Spontaneous Firing ◽  
Ca1 Pyramidal Neurons ◽  
Model Of Alzheimer’S Disease ◽  
The Mean

Introduction: Memantine (MEM) is a noncompetitive NMDAR antagonist clinically used for the treatment Alzheimer’s disease (AD) in mild to severe conditions. The present study was conducted to investigate the effects of Memantine on the spontaneous firing frequency of CA1 pyramidal neurons in rats with electrical lesion of nucleus basalis magnocellularis (NBM) as an animal model of Alzheimer's disease compared with intact adult males. Methods: In this study, adult male rats were divided into two groups. Group I (Lesion NBM, n=53) includes the following subgroups: Lesion+Saline; Sham+Saline; Lesion+MEM5mg/kg; Lesion+MEM10mg/kg; Lesion+MEM20mg/kg. And Group II (Intact, n=48) include the following subgroups: Intact+Saline; Intact+MEM3mg/kg; Intact+MEM5mg/kg; Intact+MEM10mg/kg. Extracellular single unit recording (15 min baseline+105 min after MEM or saline) was performed under urethane-anesthetized rats. Results: The results showed that the mean frequency of CA1 pyramidal neurons after saline in the Lesion+Saline (P<0.001) group significantly decreases compared with the Intact+Saline and Sham+Saline groups. In addition, after saline and memantine, the mean frequency of CA1 pyramidal neurons in the Lesion+MEM10mg/kg (P<0.01) and Lesion+MEM20mg/kg (P<0.001) groups significantly increases compared with the Lesion+Saline group. In addition the mean frequencies of CA1 pyramidal neurons in the Intact+MEM10mg/kg (P<0.001) group significantly decreases compared with the intact+saline group. Conclusion: Results showed that memantine increases the electrical activity of CA1 pyramidal neurons in rats model of Alzheimer's disease. Furthermore, in intact adult male rats, it was shown that low-dose memantine contrary to its high dose not decrease the electrical activity of CA1 pyramidal neurons.

scholarly journals Hippocampal hyperactivity in a rat model of Alzheimer’s disease

2020 ◽  
Author(s):  
Liudmila Sosulina ◽  
Manuel Mittag ◽  
Hans-Rüdiger Geis ◽  
Kerstin Hoffmann ◽  
Igor Klyubin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rat Model ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Disease Stage ◽  
Intrinsic Excitability ◽  
Ca1 Neurons ◽  
Ca1 Pyramidal Neurons ◽  
Model Of Alzheimer’S Disease

AbstractNeuronal network dysfunction is a hallmark of Alzheimer’s disease (AD). However, the underlying pathomechanisms remain unknown. We analyzed the hippocampal micronetwork in a rat model of AD at an early disease stage at the beginning of extracellular amyloid beta (Aβ) deposition. We established two-photon Ca2+-imaging in vivo in the hippocampus of rats and found hyperactivity of CA1 neurons. Patch-clamp recordings in brain slices in vitro revealed changes in the passive properties and intrinsic excitability of CA1 pyramidal neurons. Furthermore, we observed increased neuronal input resistance and prolonged action potential width in CA1 pyramidal neurons. Surprisingly, all parameters measured to quantify synaptic inhibition and excitation onto CA1 pyramidal neurons were intact suggesting a cell immanent deficit. Our data support the view that altered intrinsic excitability of CA1 neurons may precede inhibitory dysfunction at an early stage of disease progression.

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 Enduring glucocorticoid-evoked exacerbation of synaptic plasticity disruption in male rats modelling early Alzheimer’s disease amyloidosis

2021 ◽  
Author(s):  
Yingjie Qi ◽  
Igor Klyubin ◽  
Tomas Ondrejcak ◽  
Neng-Wei Hu ◽  
Michael J. Rowan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Transgenic Animals ◽  
Long Term Potentiation ◽  
Male Rats ◽  
Model Of Alzheimer’S Disease ◽  
Term Potentiation ◽  
Early Alzheimer’S Disease

AbstractSynaptic dysfunction is a likely proximate cause of subtle cognitive impairment in early Alzheimer’s disease. Soluble oligomers are the most synaptotoxic forms of amyloid ß-protein (Aß) and mediate synaptic plasticity disruption in Alzheimer’s disease amyloidosis. Because the presence and extent of cortisol excess in prodromal Alzheimer’s disease predicts the onset of cognitive symptoms we hypothesised that corticosteroids would exacerbate the inhibition of hippocampal synaptic long-term potentiation in a rat model of Alzheimer’s disease amyloidosis. In a longitudinal experimental design using freely behaving pre-plaque McGill-R-Thy1-APP male rats, three injections of corticosterone or the glucocorticoid methylprednisolone profoundly disrupted long-term potentiation induced by strong conditioning stimulation for at least 2 months. The same treatments had a transient or no detectible detrimental effect on synaptic plasticity in wild-type littermates. Moreover, corticosterone-mediated cognitive dysfunction, as assessed in a novel object recognition test, was more persistent in the transgenic animals. Evidence for the involvement of pro-inflammatory mechanisms was provided by the ability of the selective the NOD-leucine rich repeat and pyrin containing protein 3 (NLRP3) inflammasome inhibitor Mcc950 to reverse the synaptic plasticity deficit in corticosterone-treated transgenic animals. The marked prolongation of the synaptic plasticity disrupting effects of brief corticosteroid excess substantiates a causal role for hypothalamic-pituitary-adrenal axis dysregulation in early Alzheimer’s disease.

scholarly journals Treadmill exercise improves memory and increases hippocampal BDNF in a rat model of Alzheimer's Disease

2020 ◽  
Vol 24 (4) ◽  
pp. 250-256
Author(s):  
Rokhsareh Abshenas ◽  
◽  
Tayebe Artimani ◽  
Iraj Amiri ◽  
Siamak Shahidi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Avoidance Learning ◽  
Memory Impairment ◽  
Treadmill Exercise ◽  
Amyloid Β ◽  
Male Rats ◽  
Bdnf Expression ◽  
Learning Tasks ◽  
Model Of Alzheimer’S Disease

Introduction: Alzheimer’s disease is strongly correlated with learning and memory impairments. As exercise can enhance memory and learning, in this study, we have investigated the effects of treadmill exercise on memory impairment in amyloid β (Aβ)- treated rats focusing on brain-derived neurotrophic factor (BDNF) expression. Methods: Wistar male rats received intracerebroventricular (ICV) injection of Aβ and exercised on a treadmill for one month. Memory function was assessed using Morris water maze (MWM) and avoidance learning tasks. The level of BDNF was examined by the ELISA test. Results: The results of MWM and avoidance learning tasks showed that treadmill exercise could improve Aβ- induced memory impairment significantly. Moreover, BDNF expression increased following exercise in the Aβ- treated rats. Conclusion: The present results suggested that treadmill exercise may improve memory in Alzheimer’s disease by increasing BDNF level in the hippocampus.

Reduced Synaptic and Intrinsic Excitability of a Subtype of Pyramidal Neurons in the Medial Prefrontal Cortex in a Mouse Model of Alzheimer’s Disease

2021 ◽  
pp. 1-12
Author(s):  
Xiao-Qin Zhang ◽  
Le Xu ◽  
Si-Yu Yang ◽  
Lin-Bo Hu ◽  
Fei-Yuan Dong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Prefrontal Cortex ◽  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Intrinsic Excitability ◽  
Rodent Models ◽  
Morphological Complexity ◽  
Sholl Analysis ◽  
Model Of Alzheimer’S Disease

Background: Abnormal morphology and function of neurons in the prefrontal cortex (PFC) are associated with cognitive deficits in rodent models of Alzheimer’s disease (AD), particularly in cortical layer-5 pyramidal neurons that integrate inputs from different sources and project outputs to cortical or subcortical structures. Pyramidal neurons in layer-5 of the PFC can be classified as two subtypes depending on the inducibility of prominent hyperpolarization-activated cation currents (h-current). However, the differences in the neurophysiological alterations between these two subtypes in rodent models of AD remain poorly understood. Objective: To investigate the neurophysiological alterations between two subtypes of pyramidal neurons in hAPP-J20 mice, a transgenic model for early onset AD. Methods: The synaptic transmission and intrinsic excitability of pyramidal neurons were investigated using whole-cell patch recordings. The morphological complexity of pyramidal neurons was detected by biocytin labelling and subsequent Sholl analysis. Results: We found reduced synaptic transmission and intrinsic excitability of the prominent h-current (PH) cells but not the non-PH cells in hAPP-J20 mice. Furthermore, the function of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels which mediated h-current was disrupted in the PH cells of hAPP-J20 mice. Sholl analysis revealed that PH cells had less dendritic intersections in hAPP-J20 mice comparing to control mice, implying that a lower morphological complexity might contribute to the reduced neuronal activity. Conclusion: These results suggest that the PH cells in the medial PFC may be more vulnerable to degeneration in hAPP-J20 mice and play a sustainable role in frontal dysfunction in AD.

scholarly journals Evidence for Alzheimer’s disease-linked synapse loss and compensation in mouse and human hippocampal CA1 pyramidal neurons

2014 ◽  
Vol 220 (6) ◽  
pp. 3143-3165 ◽  
Author(s):  
Krystina M. Neuman ◽  
Elizabeth Molina-Campos ◽  
Timothy F. Musial ◽  
Andrea L. Price ◽  
Kwang-Jin Oh ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pyramidal Neurons ◽  
Ca1 Pyramidal Neurons ◽  
Synapse Loss ◽  
Hippocampal Ca1

scholarly journals Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau

2021 ◽  
Vol 22 (10) ◽  
pp. 5191
Author(s):  
Silvia Zampar ◽  
Oliver Wirths
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Pyramidal Neurons ◽  
Behavioral Assessment ◽  
Large Body ◽  
Amyloid Β ◽  
Tau Phosphorylation ◽  
Model Of Alzheimer’S Disease

The relationship between the two most prominent neuropathological hallmarks of Alzheimer’s Disease (AD), extracellular amyloid-β (Aβ) deposits and intracellular accumulation of hyperphosphorylated tau in neurofibrillary tangles (NFT), remains at present not fully understood. A large body of evidence places Aβ upstream in the cascade of pathological events, triggering NFTs formation and the subsequent neuron loss. Extracellular Aβ deposits were indeed causative of an increased tau phosphorylation and accumulation in several transgenic models but the contribution of soluble Aβ peptides is still controversial. Among the different Aβ variants, the N-terminally truncated peptide Aβ4–42 is among the most abundant. To understand whether soluble Aβ4–42 peptides impact the onset or extent of tau pathology, we have crossed the homozygous Tg4–42 mouse model of AD, exclusively expressing Aβ4–42 peptides, with the PS19 (P301S) tau transgenic model. Behavioral assessment showed that the resulting double-transgenic line presented a partial worsening of motor performance and spatial memory deficits in the aged group. While an increased loss of distal CA1 pyramidal neurons was detected in young mice, no significant alterations in hippocampal tau phosphorylation were observed in immunohistochemical analyses.

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