NEW SYNTHETIC CAFFEINE ANALOGS AS MODULATORS OF THE CHOLINERGIC SYSTEM

Background: Aluminum (Al) causes neurodegeneration and its toxic effects on cholinergic system in the brain is well documented. However, it is unknown whether and how Al changes oscillation patterns, driven by the cholinergic system, in the hippocampus. Objective: We studied acute effects of Al on nicotinic acetylcholine receptors (nAChRs)-mediated modulation of persistent gamma oscillations in the hippocampus. Method: The field potential recording was done in CA3 area of acute hippocampal slices. Results: Carbachol-induced gamma oscillation peak power increased (1.32±0.09mV2/Hz, P<0.01) in control conditions (without Al) by application of 10µM nicotine as compared to baseline value normalized to 1. This nicotine-induced facilitation of gamma oscillation peak power was found to depend on non-α7 nAChRs. In slices with Al pre-incubation for three to four hours, gamma oscillation peak power was reduced (5.4±1.8mV2/Hz, P<0.05) and facilitatory effect of nicotine on gamma oscillation peak power was blocked as compared to the control (18.06±2.1mV2/Hz) or one hour Al pre-incubated slices (11.3±2.5mV2/Hz). Intriguingly wash-out, after three to four hours of Al incubation, failed to restore baseline oscillation power and its facilitation by nicotine as no difference was observed in gamma oscillation peak power between Al wash-out slices (3.4±1.1mV2/Hz) and slices without washout (3.6±0.9mV2/Hz). Conclusion: This study shows that at cellular level, exposure of hippocampal tissue to Al compromised nAChR-mediated facilitation of cholinergic hippocampal gamma oscillations. Longer in vitro Al exposure caused permanent changes in hippocampal oscillogenic circuitry and changed its sensitivity to nAChR-modulation. This study will help to understand the possible mechanism of cognitive decline induced by Al.

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Alterations in the non-neuronal cholinergic system induced by in-vitro exposure to diazoxon in spleen mononuclear cells of Nile tilapia (O. niloticus)

Fish & Shellfish Immunology ◽

10.1016/j.fsi.2020.11.033 ◽

2021 ◽

Vol 108 ◽

pp. 134-141

Author(s):

G.A. Toledo-Ibarra ◽

M.I. Girón-Pérez ◽

C.E. Covantes-Rosales ◽

G.H. Ventura-Ramón ◽

G. Pérez-Sánchez ◽

...

Keyword(s):

Cholinergic System ◽

Nile Tilapia ◽

Mononuclear Cells ◽

In Vitro Exposure

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Functional connectivity of the nucleus basalis of Meynert in Lewy body dementia and Alzheimer’s disease

International Psychogeriatrics ◽

10.1017/s1041610220003944 ◽

2021 ◽

pp. 1-6

Author(s):

Julia Schumacher ◽

Alan J. Thomas ◽

Luis R. Peraza ◽

Michael Firbank ◽

John T. O’Brien ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Functional Connectivity ◽

Lewy Body ◽

Cholinergic System ◽

Structural Changes ◽

Lewy Body Dementia ◽

Occipital Cortex ◽

Nucleus Basalis ◽

Nucleus Basalis Of Meynert

ABSTRACT Cholinergic deficits are a hallmark of Alzheimer’s disease (AD) and Lewy body dementia (LBD). The nucleus basalis of Meynert (NBM) provides the major source of cortical cholinergic input; studying its functional connectivity might, therefore, provide a tool for probing the cholinergic system and its degeneration in neurodegenerative diseases. Forty-six LBD patients, 29 AD patients, and 31 healthy age-matched controls underwent resting-state functional magnetic resonance imaging (fMRI). A seed-based analysis was applied with seeds in the left and right NBM to assess functional connectivity between the NBM and the rest of the brain. We found a shift from anticorrelation in controls to positive correlations in LBD between the right/left NBM and clusters in right/left occipital cortex. Our results indicate that there is an imbalance in functional connectivity between the NBM and primary visual areas in LBD, which provides new insights into alterations within a part of the corticopetal cholinergic system that go beyond structural changes.

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