Direct detection of brain acetylcholine synthesis by magnetic resonance spectroscopy.

The cholinergic system is an important modulatory neurotransmitter system in the brain. Changes in acetylcholine concentration have been previously determined directly in animal models and human brain biopsy specimens, and indirectly, by the effects of drugs, in living humans. Here, we developed a method for direct determination of acetylcholine synthesis in living brain tissue.

Cholesterol homeostasis failure as a unifying cause of synaptic degeneration.

We previously showed that fine tuning of neural cholesterol dynamics is essential for basic synapse function, plasticity and behavior. Significant experimental evidence indicates that cholinergic function, ionotropic and metabotropic receptor machinery, excessive tau phosphorylation, the change of amyloid beta (Abeta or Abeta) biochemistry, neural oxidative stress reactions, and other features of neurodegeneration also depend on fine tuning of brain cholesterol homeostasis. This evidence suggest that (i) cholesterol homeostasis break is the unifying primary cause of sporadic and familial Alzheimer's disease (AD), neuromuscular diseases (particularly inclusion-body myositis), Niemann-Pick's type C disease and Down syndrome, and (ii) explains the overlap of neurodegenerative hallmarks across the spectrum of neurodegenerative diseases.

Alzheimer's amyloid-beta (A beta) is an essential synaptic protein, not neurotoxic junk.

Despite a decade long universal publication in favor of the view on amyloid-beta (A beta) as Alzheimer's disease culprit (solely neurotoxic for neurons and brain tissue), current scientific evidence leaves little doubt that A beta serves an essential role at synapse and in synaptic structure-functional plasticity that underlie learning and memory. Therefore, the change of A beta biology in Alzheimer's disease (as well as in a number of other human pathologies, including cardiovascular disease, neuromuscular junction disorders, NPC and Down's syndrome) may represent a physiological mechanism to compensate for impaired brain structure or function. In our own recent study A beta 1-40 rescued long term potentiation (LTP, a major model for activity-dependent CNS plasticity), while cholesterol synthesis inhibition abolished the restorative action of the A beta peptide.

Cholesterol, synaptic function and Alzheimer's disease.

We experimentally modeled neuronal cholesterol imbalance by creating an acute biochemical increase in cholesterol turnover in rat hippocampal slices. This kind of experimental set-up impairs the redistribution of cholesterol from one cell to another via lipoprotein transport. While increasing cholesterol removal or immediately afterwards, we evoked and recorded two brain waveforms, paired pulse facilitation (PPF) and long-term potentiation (LTP), which indicate neurotransmission and synaptic plasticity, respectively.

Choline in the aging brain.

Proton magnetic resonance spectroscopy has been increasingly utilized in brain research to monitor non-invasively metabolites such as N-acetyl aspartate (NAA), creatine (Cr) and choline (Cho). We present here studies of the effect of aging on the ratios of these metabolites measured in the rat brain in vivo and on choline transport and lipid synthesis in rat brain slices, in vitro. The in vivo studies indicated that the ratios of Cho/NAA and Cho/Cr increased in the aged hippocampus, whereas the ratio of Cr/NAA was similar in the aged and adult hippocampus.