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Botulinum toxin (Botox) is widely used in beauty industry and its long-term consequences can be a matter of concern. The hippocampal cholinergic system plays a significant role in memory and learning that could be affected by Botulinum toxin. However, to date, the effect of Botox on memory system has been controversial. This survey aimed to examine the effects of Botox on spatial memory, and biochemical and histological parameters of the hippocampus in male rats by using Rivastigmine (R) as a cholinesterase inhibitor that is more selective for the central nervous system (CNS). Thirty-five male Wistar rats (200-250 g) were distributed into seven groups: Sham, Botox A (3, 6, and 15 IU intramascularly) and Botox A (3, 6, and 15 IU) plus Rivastigmine (1 mg/kg intraperitoneally). Spatial memory was assessed in the Morris Water Maze (MWM) 4 weeks later. Moreover, the hippocampal tissue was removed for histopathological and biochemical analyses. Botox significantly impaired memory performance in MWM by increasing escape latency and swim distance and decreasing the time spent in the target zone. Furthermore, in the Botox groups, the level of acetylcholine decreased, while the level of the acetylcholinesterase enzyme increased significantly in the hippocampus. Also, local lesions were observed in the form of degeneration and loss of pyramidal neurons, as well as a decrease in the volume and shrinkage of the cell body and an increase in microglia in the damaged area. Rivastigmine administration alleviated biochemical and histological parameters and partially ameliorated Botox-induced impairments. In summary, rivastigmine could be a suitable protective approach for side effects of Botox in the hippocampus., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Evidence has shown that arsenic exposure, besides its toxic effects results in impairment of learning and memory, but its molecular mechanisms are not fully understood. In the present study, we examined sodium arsenite (1, 5, 10, 100nM) effects on contextual and tone memory of male rats in Pavlovian fear conditioning paradigm alone and in co-administration with β-amyloid. We detected changes in the level of caspase-3, nuclear factor kappa-B (NF-κB), cAMP response element-binding (CREB), heme oxygenase-1 and NF-E2-related factor-2 (Nrf2) by Western blot. Sodium arsenite in high doses induced significant memory impairment 9 and 16days after infusion. By contrast, low doses of sodium arsenite attenuate memory deficit in Aβ injected rats after 16days. Our data revealed that treatment with high concentration of sodium arsenite increased caspase-3 cleavage and NF-κB level, 9days after injection. Whereas, low doses of sodium arsenite cause Nrf2 and HO-1 activation and increased CREB phosphorylation in the hippocampus. These findings suggest the concentration dependent effects of sodium arsenite on contextual and tone memory. Moreover, it seems that the neuroprotective effects of ultra-low concentrations of sodium arsenite on Aβ-induced memory impairment is mediated via an increase Nrf2, HO-1 and CREB phosphorylation levels and decrease caspase-3 and NF-κB amount., (Copyright © 2016. Published by Elsevier Inc.)

In spite of characterizing the role of protein kinase A (PKA) in activating biochemical mechanisms, few studies have investigated the effects of PKA inhibitors on memory functions. In the present study, we used Pavlovian fear conditioning paradigm to evaluate memory alterations caused by two doses of H89 (as a conditional inhibitor of PKA) alone and in combination with amyloid-β (Aβ) in rats. Moreover, we used the Western blotting method to investigate the alterations in markers of transcription, oxidative stress, inflammation, and apoptosis pathways involved in memory impairment. Stereotaxic surgery was done to inject Aβ (30 ng/side) directly into the hippocampal CA1 area bilaterally and H89 (5 or 10 μM) intracerebroventricular unilaterally. One series of rats were trained 7 days after injections, then contextual and tone tests were conducted on days 8 and 9, respectively. Second series of rats were trained 14 days after the injections and tests were carried out on days 15 and 16. Our behavioral results showed that H89 (5 μM) not only has no destructive effect on memory, but also attenuates memory deficit caused by Aβ in combination groups. In contrast, H89 (10μM) has a reversible destructive effect on memory. Our molecular findings indicated that low dose of H89 increases CREB phosphorylation, Nrf2 and HO-1 which results in survival resistance to the stress. On the contrary, H89 with higher concentration leads to substantial increase of NF-κB and caspase-3 levels, which impair memory functions. In conclusion, our data suggest that H89 as a PKA inhibitor influences memory process through a dose and time dependent manner., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Several lines of evidence show that cAMP-PKA signaling pathway plays critical role in memory functions and suggest nitric oxide as an important modulator in learning and memory. In this study, we assessed the effects of intra-hippocampal infusion of H-89, a selective PKAII inhibitor, and 1400 W, a selective inducible nitric oxide synthase (iNOS) inhibitor, on spatial memory in rats. By using the Morris water maze, spatial memory retention parameters were examined 48 h after the infusions through measuring escape latency, traveled distance, and swimming speed. The rats receiving intra-hippocampal infusions of 1400 W (100 µM/side) showed a significant reduction (*P<0.05) in escape latency and traveled distance in comparison with the control saline group. In contrast, a significant increase (**P<0.01) in escape latency and traveled distance was observed after infusion of 10 µM H-89. Moreover, among combination groups, co-administration of 1400 W (400 µM/side) with 10 µM/side of H-89 caused a significant reduction (*P<0.05) in escape latency and traveled distance in comparison with the H-89 group. Also, we evaluated the molecular effects of 1400 W on the expression of choline acetyltransferase (ChAT), a cholinergic marker, in the CA1 region of the hippocampus and medial septal area (MSA). Immunohistochemical analysis of post-training bilateral intra-hippocampal infusion of 1400 W revealed a significant increase in ChAT immunoreactivity levels in both the CA1 and the MSA regions. Overall, the results suggest that 1400 W has protective effect against H89-induced spatial memory impairment. Moreover, the observed memory improvements caused by 1400 W infusions, might be due to interaction of iNOS with the cholinergic system., (© 2013 Elsevier B.V. All rights reserved.)