Stachys sieboldii Extract Supplementation Attenuates Memory Deficits by Modulating BDNF-CREB and Its Downstream Molecules, in Animal Models of Memory Impairment

Abstract

Cholinergic dysfunction, impaired brain-derived neurotrophic factor and cAMP response element binding protein (BDNF-CREB) signaling are one of the major pathological hallmarks of cognitive impairment. Therefore, improving cholinergic neurotransmission, and regulating the BDNF-CREB pathway by downregulating apoptosis genes is one strategy for inhibiting the etiology of dementia. This study evaluates the potential effects of Stachys sieboldii MIQ (SS) extract against cognitive dysfunction and its underlying mechanisms. SS supplementation for 33 days improved scopolamine-induced memory impairment symptoms in Morris water maze test and Y-maze test. SS reduced the acetylcholineesterase activity and significantly increase acetylcholine and cholineacetyltransferase activity in the brain. In the subsequent mechanism study, SS regulated the mRNA expression level of neuronal plasticity molecules such as (nerve growth factor) NGF, BDNF, CREB, and its downstream molecules such as Bcl-2 and Egr-1 by downregulating the neuronal apoptosis targets in both hippocampus and frontal cortex. Additionally, inward currents caused by SS in hippocampal CA1 neurons was partially blocked by the GABA receptor antagonist picrotoxin (50 μM), suggesting that SS acts on synaptic/extrasynaptic GABAA receptors. These findings indicate that SS may function in a way that is similar to nootropic drugs by inhibiting cholinergic abnormalities, and neuronal apoptosis targets and ultimately increasing the expression of BDNF-CREB.

Theobromine Improves Working Memory by Activating the CaMKII/CREB/BDNF Pathway in Rats

“…Albeit, there are some reports that working memory is also stored in the hippocampus, at least to some extent [51]. On the other hand, long-term memory formation mainly occurs in the hippocampus [52,53]. However, the neocortex [54] and perirhinal cortex [55,56] of the medial temporal lobe are anatomically interlinked in the formation of long-term memory [57].…”

Hesperetin, a Citrus Flavonoid, Attenuates LPS-Induced Neuroinflammation, Apoptosis and Memory Impairments by Modulating TLR4/NF-κB Signaling

“…Behavioral analysis was conducted daily (after 1 h of drug/chemical administration) according to the plan of experiment. To evaluate the memory and learning performance, MWM was conducted as described previously [29,30] with some small modifications. After receiving 2 consecutive days of training, latency (sec) was measured to assess the time taken to reach the hidden platform for 6 consecutive days.…”

Elaeagnus glabra f. oxyphylla Attenuates Scopolamine-Induced Learning and Memory Impairments in Mice by Improving Cholinergic Transmission via Activation of CREB/NGF Signaling

“…NGF, the first neurotrophin discovered, plays a pivotal role in neuronal plasticity and neurogenesis via the inhibition of CREB phosphorylation [45,46]. Impaired CREB phosphorylation is a known pathological factor of neurodegenerative disorders [47], triggering neuronal loss in the hippocampus and cortex via a pro-apoptotic process [48,49,50].…”