Longitudinal spatial mapping of lipid metabolites reveals pre-symptomatic changes in the hippocampi of Huntington's disease transgenic mice.

In Huntington's disease (HD), a key pathological feature includes the development of inclusion-bodies of fragments of the mutant huntingtin protein in the neurons of the striatum and hippocampus. To examine the molecular changes associated with inclusion-body formation, we applied MALDI-mass spectrometry imaging and deuterium pulse labelling to determine lipid levels and synthesis rates in the hippocampus of a transgenic mouse model of HD (R6/1 line). The R6/1 HD mice lacked inclusions in the hippocampus at 6 weeks of age (pre-symptomatic), whereas inclusions were pervasive by 16 weeks of age (symptomatic).

Paradoxical effects of exercise on hippocampal plasticity and cognition in mice with a heterozygous null mutation in the serotonin transporter gene.

Background And Purpose: Exercise is known to improve cognitive function, but the exact synaptic and cellular mechanisms remain unclear. We investigated the potential role of the serotonin (5-HT) transporter (SERT) in mediating these effects.

Experimental Approach: Hippocampal long-term potentiation (LTP) and neurogenesis were measured in standard-housed and exercising (wheel running) wild-type (WT) and SERT heterozygous (HET) mice.