Ability of oxime K027 to reactivate brain AChE in rats acutely poisoned by a direct acetylcholinesterase inhibitor

: Alzheimer’s disease (AD) is an age-associated nervous system disorder and a leading cause of dementia worldwide. Clinically it is described by cognitive impairment, and pathophysiologically by deposition of amyloid plaques and neurofibrillary tangles in the brain and neurodegeneration. This article reviews the pathophysiology, course of neuronal degeneration, and the various possible hypothesis of AD progression. These hypotheses include amyloid cascade, tau hyperphosphorylation, cholinergic disruption, metal dysregulation, vascular dysfunction, oxidative stress, and neuroinflammation. There is an exponential increase in the occurrence of the AD in recent few years that indicate an urgent need to develop some effective treatment. Currently, only 2 classes of drugs are available for AD treatment namely acetylcholinesterase inhibitor and NMDA receptor antagonist. Since AD is a complex neurological disorder and these drugs use a single target approach, alternatives are needed due to limited effectiveness and unpleasant side-effects of these drugs. Currently, plants have been used for drug development research especially because of their multiple sites of action and fewer side effects. Uses of some herbs and phytoconstituents for the management of neuronal disorders like AD have been documented in this article. Phytochemical screening of these plants shows the presence of many beneficial constituents like flavonoids, triterpenes, alkaloids, sterols, polyphenols, and tannins. These compounds show a wide array of pharmacological activities such as anti-amyloidogenic, anticholinesterase, and antioxidant. This article summarizes the present understanding of AD progression and gathers biochemical evidence from various works on natural products that can be useful in the management of this disease.

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Acetylcholinesterase inhibitor responsive myasthenia in a Filipino male with X-linked recessive spinal and bulbar muscular atrophy

Neurological Sciences ◽

10.1007/s10072-021-05358-0 ◽

2021 ◽

Author(s):

Roland Dominic G. Jamora ◽

Mario B. Prado ◽

Carlos L. Chua

Keyword(s):

Muscular Atrophy ◽

Acetylcholinesterase Inhibitor

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The Enhancement Effect of Acetylcholine and Pyridostigmine on Bone-Tendon Interface Healing in a Murine Rotator Cuff Model

The American Journal of Sports Medicine ◽

10.1177/0363546520988680 ◽

2021 ◽

pp. 036354652098868

Author(s):

Zhanwen Wang ◽

Yang Chen ◽

Han Xiao ◽

Shengcan Li ◽

Tao Zhang ◽

...

Keyword(s):

Rotator Cuff ◽

Rotator Cuff Repair ◽

Early Stage ◽

Drug Carrier ◽

Acetylcholinesterase Inhibitor ◽

Healing Process ◽

Enhancement Effect ◽

M2 Macrophages ◽

Fibrin Gel ◽

Cuff Repair

Background: How to improve rotator cuff healing remains a challenge. Little is known about the effect of the parasympathetic transmitter acetylcholine (ACh) and the acetylcholinesterase inhibitor pyridostigmine (PYR), both of which have anti-inflammatory properties, in the healing process of rotator cuff injury. Hypothesis: ACh and PYR could enhance bone-tendon interface healing in a murine model of rotator cuff repair. Study Design: Controlled laboratory study. Methods: A total of 160 C57BL/6 mice underwent unilateral rotator cuff repair surgery. Fibrin gel (FG) was used as a drug carrier. The mice were randomly assigned to 4 groups with 40 mice per group: FG group (received FG alone), 10-5 M ACh group (received FG containing 10-5 M ACh), 10-6 M ACh group (received FG containing 10-6 M ACh), and PYR group (received FG containing 25 µg of PYR). Ten mice in each group were euthanized at 2, 4, 8, and 12 weeks postoperatively. Histologic, immunohistochemical, and biomechanical evaluations were performed for analysis. Results: Histologically, fibrocartilage-like tissue was shown at the repaired site. The proteoglycan content of the 10-5 M ACh group was significantly increased compared with the FG group at 4 weeks. M2 macrophages were identified at the repaired site for all groups at 2 and 4 weeks. At 8 weeks, M2 macrophages withdrew back to the tendon in the FG group, but a number of M2 macrophages were retained at the repaired sites in the ACh and PYR groups. Biomechanically, failure load and stiffness of the ACh and PYR groups were significantly higher than those of the FG group at 4 weeks. The stiffness of the ACh and PYR groups was significantly increased compared with the FG group at 8 weeks ( P < .001 for all). At 12 weeks, most of the healing properties of the ACh and PYR groups were not significantly different compared with the FG group. Conclusion: ACh and PYR enhanced the early stage of bone-tendon insertion healing after rotator cuff repair. Clinical Relevance: These findings imply that ACh and PYR could serve as potential therapeutic strategies for rotator cuff healing.

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Short- and Long-Term Social Recognition Memory Are Differentially Modulated by Neuronal Histamine

Biomolecules ◽

10.3390/biom11040555 ◽

2021 ◽

Vol 11 (4) ◽

pp. 555

Author(s):

Barbara Rani ◽

Bruna Silva-Marques ◽

Rob Leurs ◽

Maria Beatrice Passani ◽

Patrizio Blandina ◽

...

Keyword(s):

Recognition Memory ◽

Histamine Release ◽

Histidine Decarboxylase ◽

Acetylcholinesterase Inhibitor ◽

Social Recognition ◽

Amnesic Effect ◽

Brain Histamine ◽

Monogamous Species ◽

Social Recognition Memory

The ability of recognizing familiar conspecifics is essential for many forms of social interaction including reproduction, establishment of dominance hierarchies, and pair bond formation in monogamous species. Many hormones and neurotransmitters have been suggested to play key roles in social discrimination. Here we demonstrate that disruption or potentiation of histaminergic neurotransmission differentially affects short (STM) and long-term (LTM) social recognition memory. Impairments of LTM, but not STM, were observed in histamine-deprived animals, either chronically (Hdc−/− mice lacking the histamine-synthesizing enzyme histidine decarboxylase) or acutely (mice treated with the HDC irreversible inhibitor α-fluoromethylhistidine). On the contrary, restriction of histamine release induced by stimulation of the H3R agonist (VUF16839) impaired both STM and LTM. H3R agonism-induced amnesic effect was prevented by pre-treatment with donepezil, an acetylcholinesterase inhibitor. The blockade of the H3R with ciproxifan, which in turn augmented histamine release, resulted in a procognitive effect. In keeping with this hypothesis, the procognitive effect of ciproxifan was absent in both Hdc−/− and αFMH-treated mice. Our results suggest that brain histamine is essential for the consolidation of LTM but not STM in the social recognition test. STM impairments observed after H3R stimulation are probably related to their function as heteroreceptors on cholinergic neurons.

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