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An evolutionary perspective on complex neuropsychiatric disease 11/27/2023

Members of the NIMH Network for Studies of Mental Disorders in Ancestrally Diverse Populations illuminate the genetic architecture of complex neuropsychiatric illnesses in the context of forces of evolution: mutation, selection, migration, and genetic drift/population structure.

Striatal dopamine integrates cost, benefit, and motivation 11/27/2023

Eshel et al. combine economic analyses with dopamine recordings and manipulations to find that dopamine release in the striatum encodes both the magnitude of a reward and how much the mouse has worked for it. Furthermore, the higher the mouse’s motivational level, the lower the reward-evoked dopamine release.

Longitudinal single-cell transcriptional dynamics throughout neurodegeneration in SCA1 11/27/2023

In neurodegeneration, vulnerable neuronal populations are highly influenced by concomitant changes in surrounding cells, including glia. Here, Tejwani et al. performed longitudinal single-nucleus profiling of the mouse and human SCA1 cerebellum, which elucidated the progressive dysregulation of Purkinje cells and revealed early transcriptional changes in oligodendroglia and unipolar brush cells.

Amelioration of Tau and ApoE4-linked glial lipid accumulation and neurodegeneration with an LXR agonist 11/22/2023

Using lipidomics coupled with immunostaining, Litvinchuk et al. demonstrate that ApoE promotes changes in cholesterol metabolism and lipid accumulation in glia of 9.5-month-old P301S mice. LXR agonist GW3965 diet and Abca1 overexpression markedly decrease tauopathy, neurodegeneration, synapse loss and behavioral deficits, neuroinflammation, and glial lipid accumulation in 9.5-month-old P301S/ApoE4 mice.