scholarly journals IL-37 expression reduces acute and chronic neuroinflammation and rescues cognitive impairment in an Alzheimer s disease mouse model

2021 ◽  
Author(s):  
Niklas Lonnemann ◽  
Shirin Hosseini ◽  
Melanie Ohm ◽  
Karsten Hiller ◽  
Charles A. Dinarello ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cognitive Abilities ◽  
Long Term Potentiation ◽  
Spine Density ◽  
Chronic Neuroinflammation ◽  
Model Of Alzheimer’S Disease ◽  
Term Potentiation ◽  
Anti Inflammatory ◽  
And Function ◽  
And Behavior

The anti-inflammatory cytokine interleukin-37 (IL-37) is a member of the IL-1 family but not expressed in mice. We used a human IL 37 (hIL-37tg) expressing mouse, which has been subjected to various models of local and systemic inflammation as well as immunological challenges. Those studies demonstrate an immune-modulatory role of IL-37 which can be characterized as an important suppressor of innate immunity. We investigated the functions of IL-37 in the CNS and explored the effects of IL-37 on neuronal architecture and function, microglia phenotype, cytokine production and behavior after inflammatory challenge by intraperitoneal LPS-injection. Reduced spine density, activated microglia phenotype and impaired long-term potentiation (LTP) were observed in wild-type mice after LPS injection, whereas hIL-37tg mice showed no impairment. In addition, we crossed the hIL-37tg mouse with an animal model of Alzheimer's disease (APP/PS1) to investigate the anti-inflammatory properties of IL-37 under chronic neuroinflammatory conditions. Our results show that IL-37 is able to limit inflammation in the brain after acute inflammatory events and prevent the loss of cognitive abilities in a mouse model of AD.

scholarly journals Torpor enhances synaptic strength and restores memory performance in a mouse model of Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christina F. de Veij Mestdagh ◽  
Jaap A. Timmerman ◽  
Frank Koopmans ◽  
Iryna Paliukhovich ◽  
Suzanne S. M. Miedema ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Memory Performance ◽  
Long Term Potentiation ◽  
Fear Memory ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
Model Of Alzheimer’S Disease ◽  
Term Potentiation

AbstractHibernation induces neurodegeneration-like changes in the brain, which are completely reversed upon arousal. Hibernation-induced plasticity may therefore be of great relevance for the treatment of neurodegenerative diseases, but remains largely unexplored. Here we show that a single torpor and arousal sequence in mice does not induce dendrite retraction and synapse loss as observed in seasonal hibernators. Instead, it increases hippocampal long-term potentiation and contextual fear memory. This is accompanied by increased levels of key postsynaptic proteins and mitochondrial complex I and IV proteins, indicating mitochondrial reactivation and enhanced synaptic plasticity upon arousal. Interestingly, a single torpor and arousal sequence was also sufficient to restore contextual fear memory in an APP/PS1 mouse model of Alzheimer’s disease. Our study demonstrates that torpor in mice evokes an exceptional state of hippocampal plasticity and that naturally occurring plasticity mechanisms during torpor provide an opportunity to identify unique druggable targets for the treatment of cognitive impairment.

scholarly journals Carvedilol Reestablishes Long-Term Potentiation in a Mouse Model of Alzheimer's Disease

2010 ◽  
Vol 21 (2) ◽  
pp. 649-654 ◽  
Author(s):  
Isabel Arrieta-Cruz ◽  
Jun Wang ◽  
Constantine Pavlides ◽  
Giulio Maria Pasinetti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Long Term Potentiation ◽  
Model Of Alzheimer’S Disease ◽  
Term Potentiation

scholarly journals Synaptic plasticity and cognitive function are disrupted in the absence of Lrp4

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Andrea M Gomez ◽  
Robert C Froemke ◽  
Steven J Burden
Keyword(s):  
Long Term Potentiation ◽  
Neurological Deficits ◽  
Spine Density ◽  
Ca1 Neurons ◽  
Form And Function ◽  
Term Potentiation ◽  
Hippocampal Ca3 ◽  
And Function ◽  
Apical Dendrites

Lrp4, the muscle receptor for neuronal Agrin, is expressed in the hippocampus and areas involved in cognition. The function of Lrp4 in the brain, however, is unknown, as Lrp4−/− mice fail to form neuromuscular synapses and die at birth. Lrp4−/− mice, rescued for Lrp4 expression selectively in muscle, survive into adulthood and showed profound deficits in cognitive tasks that assess learning and memory. To learn whether synapses form and function aberrantly, we used electrophysiological and anatomical methods to study hippocampal CA3–CA1 synapses. In the absence of Lrp4, the organization of the hippocampus appeared normal, but the frequency of spontaneous release events and spine density on primary apical dendrites were reduced. CA3 input was unable to adequately depolarize CA1 neurons to induce long-term potentiation. Our studies demonstrate a role for Lrp4 in hippocampal function and suggest that patients with mutations in Lrp4 or auto-antibodies to Lrp4 should be evaluated for neurological deficits.

Sign in / Sign up

Export Citation Format

Share Document