Immunohistochemical analysis of hippocampal butyrylcholinesterase: Implications for regional vulnerability in Alzheimer's disease

Akatsu, Hiroyasu; Abrahamson, Eric E.; Mi, Zhiping; Ikonomović, Miloš D.

doi:10.1111/neup.12241

Cited by 8 publications

(2 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both AChE and BuChE hydrolyze ACh into choline and acetate to terminate its activity at synapses. In the brain, AChE is mostly found within synaptic clefts between neurons ( 57 , 58 ), while BuChE is mainly located outside the synaptic cleft and in glial cells ( 59 , 60 ). Both AChE and BuChE are present at the mouse neuromuscular junction, but exhibit different localization patterns.…”

Section: Cholinergic Components Expressed In Immune Cellsmentioning

confidence: 99%

Expression and Function of the Cholinergic System in Immune Cells

et al. 2017

View full text Add to dashboard Cite

T and B cells express most cholinergic system components—e.g., acetylcholine (ACh), choline acetyltransferase (ChAT), acetylcholinesterase, and both muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively). Using ChATBAC-eGFP transgenic mice, ChAT expression has been confirmed in T and B cells, dendritic cells, and macrophages. Moreover, T cell activation via T-cell receptor/CD3-mediated pathways upregulates ChAT mRNA expression and ACh synthesis, suggesting that this lymphocytic cholinergic system contributes to the regulation of immune function. Immune cells express all five mAChRs (M1–M5). Combined M1/M5 mAChR-deficient (M1/M5-KO) mice produce less antigen-specific antibody than wild-type (WT) mice. Furthermore, spleen cells in M1/M5-KO mice produce less tumor necrosis factor (TNF)-α and interleukin (IL)-6, suggesting M1/M5 mAChRs are involved in regulating pro-inflammatory cytokine and antibody production. Immune cells also frequently express the α2, α5, α6, α7, α9, and α10 nAChR subunits. α7 nAChR-deficient (α7-KO) mice produce more antigen-specific antibody than WT mice, and spleen cells from α7-KO mice produce more TNF-α and IL-6 than WT cells. This suggests that α7 nAChRs are involved in regulating cytokine production and thus modulate antibody production. Evidence also indicates that nicotine modulates immune responses by altering cytokine production and that α7 nAChR signaling contributes to immunomodulation through modification of T cell differentiation. Together, these findings suggest the involvement of both mAChRs and nAChRs in the regulation of immune function. The observation that vagus nerve stimulation protects mice from lethal endotoxin shock led to the notion of a cholinergic anti-inflammatory reflex pathway, and the spleen is an essential component of this anti-inflammatory reflex. Because the spleen lacks direct vagus innervation, it has been postulated that ACh synthesized by a subset of CD4+ T cells relays vagal nerve signals to α7 nAChRs on splenic macrophages, which downregulates TNF-α synthesis and release, thereby modulating inflammatory responses. However, because the spleen is innervated solely by the noradrenergic splenic nerve, confirmation of an anti-inflammatory reflex pathway involving the spleen requires several more hypotheses to be addressed. We will review and discuss these issues in the context of the cholinergic system in immune cells.

show abstract

Section: Cholinergic Components Expressed In Immune Cellsmentioning

confidence: 99%

Expression and Function of the Cholinergic System in Immune Cells

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Meanwhile, cholinergic hypothesis, the earliest theory, is based on the deficit in acetylcholine (ACh) level, which is a cholinergic neurotransmitter that is hydrolyzed by acetylcholinesterase (AChE) [ 8 , 9 , 10 , 11 , 12 ]. Relevantly, butyrylcholinesterase (BChE), the sister enzyme of AChE of the serine hydrolase class, has broader varieties of substrates compared with AChE that can also inhibit ACh [ 13 ]; BChE has been histochemically found to accumulate in β -amyloid rich-senile plaques in the brain [ 14 , 15 , 16 , 17 ]. At present, only two drug classes, i.e., cholinesterase inhibitors (i.e., tacrine, rivastigmine, donepezil, and galanthamine) and N -methyl-D-aspartate (NMDA) antagonists (i.e., memantamine), have been used for the treatment of AD [ 18 , 19 , 20 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

A Focused Review on Cognitive Improvement by the Genus Salvia L. (Sage)—From Ethnopharmacology to Clinical Evidence

2023

View full text Add to dashboard Cite

Ethnopharmacology has been an important starting point in medical and pharmaceutical sciences for discovering drug candidates from natural sources. In this regard, the genus Salvia L., commonly known as sage, is one of the best-known medicinal and aromatic plants of the Lamiaceae family; it has been recorded as being used for memory enhancement in European folk medicine. Despite the various uses of sage in folk medicines, the records that have pointed out sage’s memory-enhancing properties have paved the way for the aforementioned effect to be proven on scientific grounds. There are many preclinical studies and excellent reviews referring to the favorable effect of different species of sage against the cognitive dysfunction that is related to Alzheimer’s disease (AD). Hence, the current review discusses clinical studies that provide evidence for the effect of Salvia species on cognitive dysfunction. Clinical studies have shown that some Salvia species, i.e., hydroalcoholic extracts and essential oils of S. officinalis L. and S. lavandulaefolia leaves in particular, have been the most prominently effective species in patients with mild to moderate AD, and these species have shown positive effects on the memory of young and healthy people. However, the numbers of subjects in the studies were small, and standardized extracts were not used for the most part. Our review points out to the need for longer-term clinical studies with higher numbers of subjects being administered standardized sage preparations.

show abstract