Capsaicin Attenuates Amyloid-β-Induced Synapse Loss and Cognitive Impairments in Mice

Abstract

Alzheimer's disease (AD) is the most common cause of progressive cognitive impairment in the aged. The aggregation of the amyloid β-protein (Aβ) is a hallmark of AD and is linked to synapse loss and cognitive impairment. Capsaicin, a specific agonist of the transient receptor potential vanilloid 1 (TRPV1), has been proven to ameliorate stress-induced AD-like pathological and cognitive impairments, but it is unclear whether TRPV1 activation can affect cognitive and synaptic functions in Aβ-induced mouse model of AD. In this study, we investigated the effects of TRPV1 activation on spatial memory and synaptic plasticity in mice treated with Aβ. To induce AD-like pathological and cognitive impairments, adult C57Bl/6 mice were microinjected with Aβ42 (100 μM, 2.5 μl/mouse, i.c.v.). Two weeks after Aβ42 microinjection, spatial learning and memory as well as hippocampal long-term potentiation (LTP) were examined. The results showed that Aβ42 microinjection significantly impaired spatial learning and memory in the Morris water maze and novel object recognition tests compared with controls. These behavioral changes were accompanied by synapse loss and impaired LTP in the CA1 area of hippocampus. More importantly, daily capsaicin (1 mg/kg, i.p.) treatment throughout the experiment dramatically improved spatial learning and memory and synaptic function, as reflected by enhanced hippocampal LTP and reduced synapse loss, whereas the TRPV1 antagonist capsazepine (1 mg/kg, i.p.) treatment had no effects on cognitive and synaptic function in Aβ42-treated mice. These results indicate that TRPV1 activation by capsaicin rescues cognitive deficit in the Aβ42-induced mouse model of AD both structurely and functionally.

TRPV1 activation alleviates cognitive and synaptic plasticity impairments through inhibiting AMPAR endocytosis in APP23/PS45 mouse model of Alzheimer’s disease

“…Thus, regulation of TRPV1 may alleviate synaptic and cognitive impairments during AD development. Indeed, our recent study has demonstrated that TRPV1 activation by CAP could improve the synaptic and cognitive functions in Aβ‐induced mouse model of AD (Chen et al, ). Jiang and colleagues have also reported that activation of TRPV1 can mitigate stress‐induced AD‐like neuropathological alterations and cognitive impairment in rats (Jiang et al, ).…”

“…Synaptic plasticity and cognitive function are significantly impaired in AD, and we therefore hypothesize that TRPV1 activation may alleviate the impairments of LTP and memory during AD progression. Indeed, our recent study has shown that TRPV1 agonist capsaicin can reverse hippocampal CA1 LTP and memory impairments in the Aβ‐induced mouse model of AD (Chen et al, ). However, exogenous Aβ treatment is hard to mimic AD development, and so far, little is known about the cellular and molecular mechanism underlying the amelioration of AD symptoms with TRPV1.…”

Memory Impairment Induced by Borna Disease Virus 1 Infection is Associated with Reduced H3K9 Acetylation

“…and transcardially perfused with N-methyl-D-glucamine (NMDG) artificial cerebral spinal fluid (ACSF) prior to decapitation as described previously [28]. The hippocampus was rapidly dissected and acute coronal hippocampal slices 400 μm thick were cut using a vibratome (VT1000 S, Leica Microsystems) in ice-cold cutting solution (NMDG ACSF) bubbled with 5% CO 2 and 95% O 2 .…”

Dielectric Constant and Conductivity of Blood Plasma: Possible Novel Biomarkers for Alzheimer’s Disease

“…Currently, there are ongoing experimental approaches that specifically focus on antiamyloid strategies because of the association of β-amyloid plaques and AD. These approaches include the development of a form of vaccine, inhibitors of the amyloidogenic enzymes γ-secretase and βsecretase, or peptides that reduce the toxic effects of β-amyloid plaques [20][21][22][23][24]. Thus far, the outcomes of these studies all agree with the fact that biomarkers for abnormal β-amyloid accumulation in the brain (hippocampus, cortex) may be a focal point to tackle AD associated with cognitive and memory dysfunction [17].…”