AGING-ASSOCIATED COGNITIVE DECLINE IS REVERSED BY D-SERINE SUPPLEMENTATION.

Brain aging is a natural process that involves structural and functional changes that lead to cognitive decline, even in healthy subjects. This detriment has been associated with N-methyl-D-aspartate receptor (NMDAR) hypofunction due to a reduction in the brain levels of D-serine, the endogenous NMDAR co-agonist. However, it is not clear if D-serine supplementation could be used as an intervention to reduce or reverse age-related brain alterations. In the present work, we aimed to analyze the D-serine effect on aging-associated alterations in cellular and large-scale brain systems that could support cognitive flexibility in rats. We found that D-serine supplementation reverts the age-related decline in cognitive flexibility, frontal dendritic spine density, and partially restored large-scale functional connectivity without inducing nephrotoxicity; instead, D-serine restored the thickness of the renal epithelial cells that were affected by age. Our results suggest that D-serine could be used as a therapeutic target to reverse age-related brain alterations.SIGNIFICANT STATEMENTAge-related behavioral changes in cognitive performance occur as a physiological process of aging. Then, it is important to explore possible therapeutics to decrease, retard or reverse aging effects on the brain. NMDA receptor hypofunction contributes to the aging-associated cognitive decline. In the aged brain, there is a reduction in the brain levels of the NMDAR co-agonist, D-Serine. However, it is unclear if chronic D-serine supplementation could revert the age-detriment in brain functions. Our results show that D-serine supplementation reverts the age-associated decrease in cognitive flexibility, functional brain connectivity, and neuronal morphology. Our findings raise the possibility that restoring the brain levels of D-serine could be used as a therapeutic target to recover brain alterations associated with aging.

The Neural Substrate of Speech Act Recognition.

Pragmatic competence demands linguistic, but also communicative, social and cognitive competence. Successful use of language in social interaction requires mutual understanding of the speaker's intentions; without it, a conversation cannot proceed. The term speech act refers to what a speaker intends to accomplish when saying something. The purpose of this study was to contribute to the identification of the neural substrate of speech act recognition and to the characterization of the cognitive processes that may be involved. The recognition of speech acts resulted in greater activation of frontal regions, precuneus and posterior cingulate gyrus. From all cognitive and behavioral measures obtained, only the scores in mental flexibility predicted the change in blood oxygen level dependent (BOLD) signal in the precuneus. These results, support the idea that speech act recognition requires the inference of intention, executive functions, including memory and entails the activation of areas of social cognition that participate in several brain networks i.e., the Intention Processing, the Default Mode and Theory of Mind networks, and areas involved in planning and guiding behavior.

Testosterone is related to GABA+ levels in the posterior-cingulate in unmedicated depressed women during reproductive life.

BACKGROUND: The role of testosterone (T) in the pathophysiology of affective disorders and anxiety is broadly supported. Evidence suggests that T has anxiolytic and antidepressant properties. One proposed route for the central effects of T is its interaction with the gamma-aminobutyric acid (GABA) system. We explored the relationship between T levels and GABA+ levels in anterior-cingulate (ACC) and the posterior-cingulate (PCC) regions in depressed women, using magnetic resonance spectroscopy (1H-MRS). METHODS: Twenty-one depressed patients with regularly cycling who were not taking hormonal or psychotropic drugs were recruited. We assessed severity of depression using the Hamilton Depression Rating Scale (HDRS). Blood samples were taken for quantification of free (FT) and total testosterone (TT) on the day of the magnetic resonance (MR) scan. We evaluated GABA+ levels in the PCC and ACC, using the Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy (HERMES) sequence. Pearson correlations were used to evaluate the association between FT, TT, GABA+ concentrations, and HDRS scores. RESULTS: TT and FT levels were positively correlated with GABA+ levels in the PCC. No correlation was observed between T levels and GABA+ levels in the ACC. The HDRS total scores correlated negatively with FT levels. LIMITATIONS: Limitations include the cross-sectional evaluation and the lack of a comparative healthy group. CONCLUSIONS: Our findings suggest that the potential anxiolytic and antidepressant properties of T are related to increased GABA+ levels in the PCC. This observation may contribute to increased understanding of the role of T in depressive and anxiety symptoms in women.

Event-Related Functional Magnetic Resonance Images during the Perception of Phantom Limb. A Brushing Task.

The phantom limb phenomenon has been used in amputee patients as a paradigm to study plasticity, mainly of the sensorimotor cortex. Nevertheless, most functional studies have been done in upper limb amputee patients using magnetoencephalography and functional magnetic resonance image imaging (fMRI). In addition, the actual experience of phantom limb sensation has not been widely used to study the neural mechanism of the human brain as a conscious knowledge of the phantom limb perception like the integration of the body image in amputee patients. fMRI studies of patients with lower limb amputation have recently been published, but none of these used an event-related design to try to observe only the stimulus application, correlating images with the subject's indication of phantom perception and discarding images with no phantom perception. In this work, we used the event-related fMRI design in two right-handed patients with identical right, transfemoral amputations, performing the same sensitive stimulation in a 3.0 T MR scanner. For comparison, we applied the same paradigm to six control subjects to compare the resulting functional maps. We found areas with statistical significance in the sensorimotor cortex contralateral to the site of stimulation, in the parietal lobe in Brodmann areas 3 in both cases (Patients and Control Subjects), but we also found activation in the Brodmann areas 6, 40, and 5 with stimulation of the stump. We observed a specific activation of the frontoparietal circuit during phantom limb perception in both amputee patients.