No abstract

No abstract

Down syndrome is the most common genetic cause of intellectual disability and occurs due to the trisomy of human chromosome 21. Adolescent and adult brains from humans with Down syndrome exhibit various neurological phenotypes including a reduction in the size of the corpus callosum, hippocampal commissure and anterior commissure. However, it is unclear when and how these interhemispheric connectivity defects arise. Using the Ts65Dn mouse model of Down syndrome, we examined interhemispheric connectivity in postnatal day 0 (P0) Ts65Dn mouse brains. We find that there is no change in the volume of the corpus callosum or anterior commissure in P0 Ts65Dn mice. However, the volume of the hippocampal commissure is significantly reduced in P0 Ts65Dn mice, and this may contribute to the impaired learning and memory phenotype of this disorder. Interhemispheric connectivity defects that arise during development may be due to disrupted axon growth. In line with this, we find that developing hippocampal neurons display reduced axon length in vitro, as compared to neurons from their euploid littermates. This study is the first to report the presence of defective interhemispheric connectivity at the time of birth in Ts65Dn mice, providing evidence that early therapeutic intervention may be an effective time window for the treatment of Down syndrome.3

No abstract

Obesity is one of the most prevalent diseases quietly plaguing this nation. With predictions of its prevalence nearing almost 50% of the adult US population by the end of this decade, it is paramount to identify underlying mechanisms. Characterized by its imbalance of energy intake and energy expenditure, obesity can be countered by amplifying metabolic rate, including inducing thermogenesis. Primarily research has sought to understand adipose tissue thermogenesis, leaving little attention directed toward the brain mechanisms that regulate skeletal muscle thermogenesis. Published evidence from our research program has established that exposure to predator odor (PO) evokes a robust thermogenic response in the skeletal muscle, suggesting that PO works through an unknown brain mechanism causing the thermogenic response. This metabolic response and the stimulation by predator threat each implicate the dorsomedial subregion of the ventromedial hypothalamus (dmVMH), and more specifically, the steroidogenic factor 1 (SF1) cells within it, as a region for further investigation. We hypothesize that SF1 neurons of dmVMH are a key node for predator odor‐induced muscle thermogenesis. We use designer receptors exclusively activated by designer drugs (DREADD) delivered using a viral vector to SF1‐Cre mice to assess this hypothesis. Utilizing DREADD technology, we stimulated the SF1 cells in the presence of a control odor or PO (ferret odor). Here, we analyze preliminary data looking at the muscle thermogenesis of SF1 Cre mice that have been bilaterally injected with mCherry control vector or an excitatory DREADD vector. Using clozapine‐N‐oxide (CNO) and manipulation of context (i.e., with or without the presence of PO), we have detected increases in thermogenesis with each PO exposure and CNO activation of SF1 neurons. However, these data provide little to no evidence of DREADD‐induced amplification of the PO‐induced thermogenesis. Our preliminary data supports the importance of SF1 neurons and their role in regulating PO‐induced skeletal muscle thermogenesis.