Search

Nicotinic acetylcholine receptor subtype α4β2 is considered important in the regulation of attention and memory, and cholinergic degeneration is known as one pathophysiology of Alzheimer's disease. Brain amyloid-β protein deposition is also a key pathological marker of Alzheimer's disease. Recent amyloid-β imaging has shown many cognitively normal subjects with amyloid-β deposits, indicating a missing link between amyloid-β deposition and cognitive decline. To date, the relationship between the α4β2 nicotinic acetylcholine receptor and amyloid-β burden has not been elucidated in vivo. In this study we investigated the relation between α4β2 nicotinic acetylcholine receptor availability in the brain, cognitive functions and amyloid-β burden in 20 non-smoking patients with Alzheimer's disease at an early stage and 25 age-matched non-smoking healthy elderly adults by measuring levels of α4β2 nicotinic acetylcholine receptor binding estimated from a simplified ratio method (BPRI) and Logan plot-based amyloid-β accumulation (BPND) using positron emission tomography with α4β2 nicotinic acetylcholine receptor tracer (18)F-2FA-85380 and (11)C-Pittsburgh compound B. The levels of tracer binding were compared with clinical measures for various brain functions (general cognition, episodic and spatial memory, execution, judgement, emotion) using regions of interest and statistical parametric mapping analyses. Between-group statistical parametric mapping analysis showed a significant reduction in (18)F-2FA-85380 BPRI in the cholinergic projection region in patients with Alzheimer's disease with a variety of (11)C-Pittsburgh compound B accumulation. Spearman rank correlation analyses showed positive correlations of (18)F-2FA-85380 BPRI values in the medial frontal cortex and nucleus basalis magnocellularis region with scores of the Frontal Assessment Battery (a test battery for executive functions and judgement) in the Alzheimer's disease group (P < 0.05 corrected for multiple comparison), and also positive correlations of the prefrontal and superior parietal (18)F-2FA-85380 BPRI values with the Frontal Assessment Battery score in the normal group (P < 0.05 corrected for multiple comparison). These positive correlations indicated an in vivo α4β2 nicotinic acetylcholine receptor role in those specific functions that may be different from memory. Both region of interest-based and voxelwise regression analyses showed a negative correlation between frontal (11)C-Pittsburgh compound B BPND and (18)F-2FA-85380 BPRI values in the medial frontal cortex and nucleus basalis magnocellularis region in patients with Alzheimer's disease (P < 0.05 corrected for multiple comparison). These findings suggest that an impairment of the cholinergic α4β2 nicotinic acetylcholine receptor system with the greater amount of amyloid deposition in the system plays an important role in the pathophysiology of Alzheimer's disease.

Learning-set (LS) is a property of insight and hypothesis testing characterized by the ability to solve novel problems based on previous experiences with problem solving. However, the neural organization and mechanisms underlying LS remain unclear. To further characterize this process, positron emission tomography (PET) studies with [15O]H2O were performed to measure regional cerebral blood flow (rCBF) during the learning phase of the two-choice visual discrimination task under the LS paradigm in rhesus monkeys. When comparing studies before and after LS formation, the orbitofrontal and lateral prefrontal cortices were differentially activated, and functional connections between these structures and the striatum, which contributes to habit learning, were altered. We conclude that changes in the lateral prefrontal cortex during problem solving may contribute to the executive function of working memory and also inhibit control of a primitive learning system, thereby promoting LS formation.

To define the cortical areas that subserve spatial working memory in a nonhuman primate, we measured regional cerebral blood flow (rCBF) with [(15)O]H(2)O and positron emission tomography while monkeys performed a visually guided saccade (VGS) task and an oculomotor delayed-response (ODR) task. Both Statistical Parametric Mapping and regions of interest-based analyses revealed an increase of rCBF in the area surrounding the principal sulcus (PS), the superior convexity, the anterior bank of the arcuate sulcus (AS), the lateral orbitofrontal cortex (lOFC), the frontal pole (FP), the anterior cingulate cortex (ACC), the lateral bank of the intraparietal sulcus (lIPS) and the prestriate cortex. In the prefrontal cortex (PS, superior convexity, AS, lOFC and FP), rCBF values correlated positively with ODR task performance scores. From the hippocampus, rCBF values correlated negatively with ODR task performance. From the AS, superior convexity, lOFC, FP, ACC and lIPS, rCBF values of the PS correlated positively with rCBF values and negatively with hippocampus rCBF values. These results suggest that neural circuitry in the prefrontal cortex directly contributes the spatial working memory processes and that, in spatial working memory processes, the posterior parietal cortex and hippocampus have a different role to the prefrontal cortex.

The ammonium ion is an indispensable nitrogen source for crops, especially paddy rice ( Oryza sativa L. cv Nipponbare). Until now, it has been impossible to measure ammonium uptake and nitrogen movement in plants in real time. Using the new technologies of PETIS (positron emitting tracer imaging system) and PMPS (positron multi-probe system), we were able to visualize the real time translocation of nitrogen and water in rice plants. We used positron-emitting 13 N-labeled ammonium ( 13 NH 4 + ) and 15 O-water to monitor the movement. In plants cultured under normal conditions, 13 NH 4 + supplied to roots was taken up, and a 13 N signal was detected at the discrimination center, the basal part of the shoots, within 2 minutes. This rapid translocation of 13 N was almost completely inhibited by a glutamine synthetase inhibitor, methionine sulfoximine. In general, nitrogen deficiency enhanced 13 N translocation to the discrimination center. In the dark, 13 N translocation to the discrimination center was suppressed to 40% of control levels, whereas 15 O-water flow from the root to the discrimination center stopped completely in the dark. In abscisic acid-treated rice, 13 N translocation to the discrimination center was doubled, whereas translocation to leaves decreased to 40% of control levels. Pretreatment with NO 3 − for 36 hours increased 13 N translocation from the roots to the discrimination center to 5 times of control levels. These results suggest that ammonium assimilation (from the roots to the discrimination center) depends passively on water flow, but actively on NH 4 + -transporter(s) or glutamine synthetase(s).

(2002) reported that a mixture of hexenol and hexenal wasaccepted as a pleasant odor and it decreased the amplitude of anevent-related potential (P300). However, the neural mechanisms ofthe effect of hexenol and hexenal are almost completely unknown.We studied its effect on prevention and/or recovery from fatigue,through analyzing the behavioral performance (reaction time, RT)of monkeys during repetition of a simple visual discrimination taskand the autonomic function as judged by acceleration plethysmog-raphy (APG) during a mental task [advanced trail making test(ATMT), continuously loaded for 4 h] in human volunteers. More-over, we investigated changes in regional cerebral blood flow (rCBF)during green-odor stimulation using positron emission tomography(PET) in monkeys.