α7 nicotinic ACh receptors are necessary for memory recovery and neuroprotection promoted by attention training in amyloid‐β‐infused mice

Abstract

Background and Purpose Attention training reverses the neurodegeneration and memory loss promoted by infusion of amyloid‐β (Aβ) peptide in rats and increases the density of α7 nicotinic ACh receptors (α7nAChRs) in brain areas related to memory. Hence, we aimed to assess the role of α7nAChRs in the memory recovery promoted by attention training. Experimental Approach C57Bl/6 mice were chronically infused with Aβ, Aβ plus the α7 antagonist methyllycaconitine (MLA), or MLA alone. Control animals were infused with vehicle. Animals were subjected weekly to the active avoidance shuttle box for 4 weeks (attention training). The brain and serum were collected for biochemical and histological analysis. Key Results Aβ caused cognitive impairment, which was reversed by the weekly training, whereas Aβ + MLA also promoted memory loss but with no reversal with weekly training. MLA alone also promoted memory loss but with only partial reversal with the training. Animals infused with Aβ alone showed senile plaques in hippocampus, no change in BDNF levels in cortex, hippocampus, and serum, but increased AChE activity in cortex and hippocampus. Co‐treatment with MLA increased AChE activity and senile plaque deposition in hippocampus as well as reducing BDNF in hippocampus and serum, suggesting a lack of α7nAChR function leads to a loss of neuroprotection mechanisms. Conclusions and Implications The α7nAChR has a determinant role in memory recovery and brain resilience in the presence of neurodegeneration promoted by Aβ peptide. These data support further studies concerning these receptors as pharmacological targets for future therapies.

Caracterização de marcadores relacionados à potenciação de longa duração (LTP) em camundongos com envelhecimento acelerado (SAMP-8) sob tratamento crônico com microdose de lítio.

“…In postsynaptic neurons, α7 nicotinic receptor activation induces the activity of CaMK-IV and transcription factors such as CREB. Recently our group showed that α7 nicotinic receptor blockade prevented memory retrieval in mice submitted to an experimental model of neurodegeneration (Telles-Longui et al, 2019). In the present work, SAMP-8 presented a significant decrease in the density of α7nAChR, when compared to SAMR-1, which may be related to the important memory loss observed.…”

α7 Nicotinic Acetylcholine Receptor May Be a Pharmacological Target for Perioperative Neurocognitive Disorders

“…The current results are consistent with previous reports on AD. A recent study found that cotreatment with MLA promoted the reduction of BDNF in the hippocampus and worsened Aβ-induced cognitive impairment, suggesting a determinant role of α7nAChR in BDNF expression and memory recovery in AD (Telles-Longui et al, 2019). Chen et al has also reported that α7nAChR blockade could inhibit the reverse of hippocampal BDNF and abolish the neuroprotective effects of simvastatin in Aβ 25-35 -mice, an inhibitor of 3-hydroxy-3-methyl-glytarylcoenzyme reductase, which is effective in improving cognition in AD patients (Wang et al, 2015).…”

Neuroprotective Effects of Cholinesterase Inhibitors: Current Scenario in Therapies for Alzheimer’s Disease and Future Perspectives

“…In mammalian brain cells, the most commonly found nAChRs are the α4β2 heteromeric (α4β2-nAChR) and the α7 homomeric subunit–α7 nicotinic ACh receptor (α7-nAChR) [ 100 ], whose importance in AD treatment has been widely examined. For example, the stimulation of α7-nAChRs contributes to memory formation and consolidation [ 96 ] and cellular recovery after Aβ-induced neurotoxicity in mice [ 97 ]. On the other hand, the blockade of α7-nAChRs induces cognitive deficits in mice [ 98 ].…”