Elia, A. | bioRxiv Science

bioRxiv2025

Influence of sustained cognitive loading on finger circulatory and thermoperceptual responsiveness to localized cooling

Our aim was to examine whether finger vasomotor and thermoperceptual responses to local cooling would be modulated by sustained cognitive loading. To this end, finger temperature, circulatory (i.e., cutaneous vascular conductance, CVC) and perceptual responses were monitored, in twelve healthy men, during and after a 30-min hand immersion in 8{degrees}C water, performed either immediately after a 60-min continual execution of a cognitive task battery (cognitive[->]cold trial), or during the simultaneous performance of the cognitive task (cognitive+cold trial). Subjects responses were compared with those obtained in a control cold-provocation trial, wherein they watched an emotionally-neutral documentary. The cognitive task temporary enhanced the perceived levels of mental effort and fatigue in both intervention trials. In the cognitive[->]cold trial, the cold-induced reduction in finger CVC and increase in mean arterial pressure were blunted (P < 0.01), and the thermal discomfort was alleviated (P = 0.05). In the cognitive+cold trial, no intertrial differences were noted during the cold-water immersion phase (P [≥] 0.28), but the finger CVC was enhanced during the last part of the rewarming phase (P = 0.05). Present findings, therefore, demonstrate that (i) in moderately mentally-fatigued individuals, finger cold-induced vasoconstriction is transiently attenuated, and thermal discomfort is mitigated, and (ii) superimposition of cognitive loading on cold stress does not alter finger vasoreactivity or thermosensitivity during cooling, but facilitates finger reperfusion following cooling.

neuroscience↗

bioRxiv2023

Amyloid β induces cardiac dysfunction and neuro-signaling impairment in the heart of an Alzheimer's disease model

While a link between cardiovascular risk factors and increased Alzheimers disease (AD) risk has been reported, it remains unclear whether AD pathology has a direct effect on cardiac function and myocardial innervation. AD and amyloidosis are known to impair neuronal function and affect brain neurotrophic factors (NGF and BDNF) expression. Amyloid aggregates and neuro-signaling impairments may also expose AD patients to peripheral nervous system deficits, promoting cardiac disorders. Here, we characterize cardiac physiology, amyloid pathology, neurotrophic factors loss, and the impoverishment of cardiac neuronal fibers in Tg2576-AD mice hearts, human cardiomyocytes in culture, and human AD post-mortem left ventricular (LV) heart tissue. We reveal that Tg2576 animals exhibit increased myocardial fibrosis, amyloid {beta} (A{beta}) deposition, and brain/heart-axis neurotrophic deficiencies, resulting in myocardial denervation and cardiac dysfunction. A{beta} oligomers reduce BDNF expression in both human immortalized and iPSC-derived cardiomyocytes, by disrupting TrkB/CREB signaling. Analysis of human LV AD post-mortem tissue confirmed cell and animal results. Our findings elucidate a previously unknown mechanism of A{beta}-induced cardiac neurotrophic signaling dysregulation, underscoring the relevance of heart degeneration in AD. Translational PerspectiveThis research identified cardiac amyloid pathology, neurotrophic factor depletion, and reduced myocardial nerve function in a transgenic model of cerebral amyloidosis (Tg2576) and in human AD heart tissue. These findings carry significant diagnostic and therapeutic implications, emphasizing the role of neuro-signaling disruption in cardiac physiology impairment linked to AD. Our study advocates for considering cardiac complications in AD management and paves the way for future precision medicine approaches to enhance systemic clinical strategies for treating AD, proposing the cardiac neurotrophic signaling pathway as a potential therapeutic target.

molecular biology↗