Personal Mastery Attenuates the Association between Greater Perceived Discrimination and Lower Amygdala and Anterior Hippocampal Volume in a Diverse Sample of Older Adults.

There is limited research investigating whether perceived discrimination influences brain structures that subserve episodic memory, namely the hippocampus and amygdala. Our rationale for examining these regions build on their known sensitivity to stress and functional differences along the long-axis of the hippocampus, with the anterior hippocampus and amygdala implicated in emotional and stress regulation. We defined perceived discrimination as the unfair treatment of one group by a dominant social group without the agency to respond to the event. A potential moderator of perceived discrimination is personal mastery, which we operationally defined as personal agency. Our primary goals were to determine whether perceived discrimination correlated with amygdala and anterior hippocampal volume, and if personal mastery moderated these relationships. Using FreeSurfer 7.1.0, we processed T1-weighted images to extract bilateral amygdala and hippocampal volumes. Discrimination and personal mastery were assessed via self-report (using the Experiences of Discrimination and Sense of Control questionnaires, respectively). Using multiple regression, greater perceived discrimination correlated with lower bilateral amygdala and anterior hippocampal volume, controlling for current stress, sex, education, age, and intracranial volume. Exploratory subfield analyses showed these associations were localized to the anterior hippocampal CA1 and subiculum. As predicted, using a moderation analysis, personal mastery attenuated the relationship between perceived discrimination and amygdala and anterior hippocampal volume. Here, we extend our knowledge on perceived discrimination as a salient psychosocial stressor with a neurobiological impact on brain systems implicated in stress, memory, and emotional regulation, and provide evidence for personal mastery as a moderating factor of these relationships.

Sonic Hedgehog Pathway Modulation Normalizes Expression of Olig2 in Rostrally Patterned NPCs With Trisomy 21.

The intellectual disability found in people with Down syndrome is associated with numerous changes in early brain development, including the proliferation and differentiation of neural progenitor cells (NPCs) and the formation and maintenance of myelin in the brain. To study how early neural precursors are affected by trisomy 21, we differentiated two isogenic lines of induced pluripotent stem cells derived from people with Down syndrome into brain-like and spinal cord-like NPCs and promoted a transition towards oligodendroglial fate by activating the Sonic hedgehog (SHH) pathway. In the spinal cord-like trisomic cells, we found no difference in expression of OLIG2 or NKX2.2, two transcription factors essential for commitment to the oligodendrocyte lineage. However, in the brain-like trisomic NPCs, OLIG2 is significantly upregulated and is associated with reduced expression of NKX2.2. We found that this gene dysregulation and block in NPC transition can be normalized by increasing the concentration of a SHH pathway agonist (SAG) during differentiation. These results underscore the importance of regional and cell type differences in gene expression in Down syndrome and demonstrate that modulation of SHH signaling in trisomic cells can rescue an early perturbed step in neural lineage specification.