Aging brain

About: Aging brain is a research topic. Over the lifetime, 1255 publications have been published within this topic receiving 66405 citations.

Aryl Hydrocarbon Receptor in Post-Mortem Hippocampus and in Serum from Young, Elder, and Alzheimer’s Patients

Abstract: One of the characteristics of the cerebral aging process is the presence of chronic inflammation through glial cells, which is particularly significant in neurodegeneration. On the other hand, it has been demonstrated that the aryl hydrocarbon receptor (AHR) participates in the inflammatory response. Currently, evidence in animal models shows that the hallmarks of aging are associated with changes in the AHR levels. However, there is no information concerning the behavior and participation of AHR in the human aging brain or in Alzheimer’s disease (AD). We evaluated the expression of AHR in human hippocampal post-mortem tissue and its association with reactive astrocytes by immunohistochemistry. Besides this, we analyzed through ELISA the AHR levels in blood serum from young and elder participants, and from AD patients. The levels of AHR and glial fibrillar acid protein were higher in elder than in young post-mortem brain samples. AHR was localized mainly in the cytosol of astrocytes and displayed a pattern that resembles extracellular vesicles; this latter feature was more conspicuous in AD subjects. We found higher serum levels of AHR in AD patients than in the other participants. These results suggest that AHR participates in the aging process, and probably in the development of neurodegenerative diseases like AD.

Targeting age-related differences in brain and cognition with multimodal imaging and connectome topography profiling.

Abstract: Aging is characterized by accumulation of structural and metabolic changes in the brain. Recent studies suggest transmodal brain networks are especially sensitive to aging, which, we hypothesize, may be due to their apical position in the cortical hierarchy. Studying an open-access healthy cohort (n = 102, age range = 30-89 years) with MRI and Aβ PET data, we estimated age-related cortical thinning, hippocampal atrophy and Aβ deposition. In addition to carrying out surface-based morphological and metabolic mapping experiments, we stratified effects along neocortical and hippocampal resting-state functional connectome gradients derived from independent datasets. The cortical gradient depicts an axis of functional differentiation from sensory-motor regions to transmodal regions, whereas the hippocampal gradient recapitulates its long-axis. While age-related thinning and increased Aβ deposition occurred across the entire cortical topography, increased Aβ deposition was especially pronounced toward higher-order transmodal regions. Age-related atrophy was greater toward the posterior end of the hippocampal long-axis. No significant effect of age on Aβ deposition in the hippocampus was observed. Imaging markers correlated with behavioral measures of fluid intelligence and episodic memory in a topography-specific manner, confirmed using both univariate as well as multivariate analyses. Our results strengthen existing evidence of structural and metabolic change in the aging brain and support the use of connectivity gradients as a compact framework to analyze and conceptualize brain-based biomarkers of aging.

The Biology and Pathobiology of Glutamatergic, Cholinergic, and Dopaminergic Signaling in the Aging Brain.

Abstract: The elderly population is growing worldwide, with important health and socioeconomic implications. Clinical and experimental studies on aging have uncovered numerous changes in the brain, such as decreased neurogenesis, increased synaptic defects, greater metabolic stress, and enhanced inflammation. These changes are associated with cognitive decline and neurobehavioral deficits. Although aging is not a disease, it is a significant risk factor for functional worsening, affective impairment, disease exaggeration, dementia, and general disease susceptibility. Conversely, life events related to mental stress and trauma can also lead to accelerated age-associated disorders and dementia. Here, we review human studies and studies on mice and rats, such as those modeling human neurodegenerative diseases, that have helped elucidate (1) the dynamics and mechanisms underlying the biological and pathological aging of the main projecting systems in the brain (glutamatergic, cholinergic, and dopaminergic) and (2) the effect of defective glutamatergic, cholinergic, and dopaminergic projection on disabilities associated with aging and neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. Detailed knowledge of the mechanisms of age-related diseases can be an important element in the development of effective ways of treatment. In this context, we briefly analyze which adverse changes associated with neurodegenerative diseases in the cholinergic, glutaminergic and dopaminergic systems could be targeted by therapeutic strategies developed as a result of our better understanding of these damaging mechanisms.

Alterations in calcium antagonist receptors and calcium content in senescent brain and attenuation by nimodipine and nicardipine.

Abstract: Characteristics of L- and N-type calcium (Ca++) channel antagonist receptors in brains of senescence-accelerated prone mouse (SAMP8) showing age-related deterioration of learning and memory were examined by using (+)-[3H]PN 200-110 and [125I]omega-conotoxin GVIA as radioligands. There was a tendency toward consistent decrease in Bmax for both radioligands in seven brain regions of SAMP8 compared with the control mouse. The reduction in (+)-[3H]Pn 200-110 binding sites was statistically significant in the hippocampus, midbrain and pons/medulla oblongata, and that in [125I]omega-conotoxin binding sites was significant in the cerebral cortex, corpus striatum and pons/medulla oblongata. On the other hand, there was a marked elevation in Ca++ content in the brain of SAMP8. Chronic p.o. administration (0.3, 1 and 3 mg/kg/day for 3 weeks) of nimodipine and nicardipine to SAMP8 caused a significant increase in the Bmax values of (+)-[3H]PN 200-110 binding in the cerebral cortex and hippocampus. This may reflect up-regulation of brain Ca++ channel antagonist receptors as a result of the prolonged blockade by nimodipine and nicardipine. On the other hand, similar administration of amlodipine and nilvadipine failed to produce an enhancement of Bmax values of (+)-[3H]PN 200-110 binding, whereas both drugs at high doses evoked a significant increase in the apparent dissociation constant. Furthermore, the brain Ca++ content in SAMP8 was markedly reduced by chronic p.o. administration of Ca++ channel antagonists, and the decrease was equivalently observed for all of four 1,4-dihydropyridine antagonists in spite of the difference in the effect on brain receptors. In conclusion, the present study suggests that there is an altered Ca++ homeostasis in the SAMP8 brain that is effectively attenuated by chronic administration of nimodipine and nicardipine. Hence SAMP8 may be a suitable animal model for evaluating the therapeutic effects of Ca++ channel antagonists on neurological disorders associated with the aging brain.