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During aging, alterations in astrocyte phenotype occur in areas associated with age-related cognitive decline, including hippocampus. Previous work reported subregion-specific changes in surface, volume, and soma size of hippocampal astrocytes during physiological aging. Herein we extensively analyzed, by morphometric analysis, fine morphological features of GFAP+ astrocytes in young (6-month-old) and middle-aged (14-month-old) male mice. We observed remarkable heterogeneity in the astrocytic response to aging in distinct subfields and along the dorsoventral axis of hippocampus and in entorhinal cortex. In middle-aged mice dorsal granule cell and molecular layers, but not hilus, astrocytes underwent remarkable increase in their morphological complexity. These changes were absent in ventral Dentate Gyrus (DG). In addition, in entorhinal cortex, the major input to dorsal DG, astrocytes underwent remarkable atrophic changes in middle-aged mice. Since dorsal DG, and not ventral DG, is involved in cognitive functions, these findings appear worth of further evaluation. Our findings also suggest an additional level of complexity in the structural changes associated with brain aging. • Aging affects astrocyte morphology in a region- and subregion-specific manner. • In 14 versusvs 6 mo-old mice, dorsal GCL and ML astrocytes increase complexity. • Hilar astrocyte complexity is not different in 6 and 14-month old mice. • Ventral GCL and ML astrocytes have similar complexity at 6 and 14 months of age. • In 14 mo-old mice EC astrocytes undergo remarkable complexity reduction. [ABSTRACT FROM AUTHOR]

• Aging increases morphological complexity of astrocytes in SNpc, but not in SNpr. • In SNpc structural remodelling is not accompanied by changes in GFAP expression. • Aging reduces GLT1 gene expression only in SNpc, not in SNpr. • Age-dependent alterations in astroglial functions may occur in SNpc. Currently, little is known about the impact of aging on astrocytes in substantia nigra pars compacta (SNpc), where dopaminergic neurons degenerate both in physiological aging and in Parkinson's disease, an age-related neurodegenerative disorder. We performed a morphometric analysis of GFAP+ astrocytes in SNpc and, for comparison, in the pars reticulata (SNpr) of young (4–6 months), middle-aged (14–17 months) and old (20–24 months) C57BL/6J male mice. We demonstrated an age-dependent increase of structural complexity only in astrocytes localized in SNpc, and not in SNpr. Astrocytic structural remodelling was not accompanied by changes in GFAP expression, while GFAP increased in SNpr of old compared to young mice. In parallel, transcript levels of selected astrocyte-enriched genes were evaluated. With aging, decreased GLT1 expression occurred only in SNpc, while xCT transcript increased both in SNpc and SNpr, suggesting a potential loss of homeostatic control of extracellular glutamate only in the subregion where age-dependent neurodegeneration occurs. Altogether, our results support an heterogenous morphological and biomolecular response to aging of GFAP+ astrocytes in SNpc and SNpr. [ABSTRACT FROM AUTHOR]

[Display omitted] Targeted delivery of drugs into specific cancer cells is an effective way to enhance the efficacy and minimize the side effects of therapy. Prostate malignant cells overexpress the prostate-specific membrane antigen (PSMA), a membrane protein that may be a valid target for selective drug administration. To target prostate cancer cells, a β-cyclodextrin perfunctionalised with dipeptide-like urea arms, a well-established mimic of a selective ligand against PSMA, is herein reported, to develop a multivalent drug delivery and targeting system. Firstly, fluorescein was used to validate the system on cells that express high levels of PSMA (prostate tumoral cells, LNCap) or very low levels of PSMA (non-tumoral cells, Hek293T). Then, the antineoplastic agent doxorubicin complexed with β-cyclodextrin functionalized with PSMA-like ligand takes less time to induce cytotoxicity on LNCap cells compared to doxorubicin alone. This might represent a promising drug-delivery approach to selectively target prostate cancer cells. [ABSTRACT FROM AUTHOR]