The homeodomain transcription factor Nkx2.1 is expressed in the pallidal (subcortical) telencephalon, including the medial ganglionic eminence (MGE) and preoptic area. Studies have shown that Nkx2.1 is required for normal patterning of the MGE and for the specification of the parvalbumin (PV)- and somatostatin (SST)-expressing cortical interneurons. To define the contribution of Nkx2.1 lineages to neurons in the mature telencephalon, we have generated transgenic mice carrying the genomic integration of a modified bacterial artificial chromosome (BAC) in which the second exon of Nkx2.1 is replaced by the Cre recombinase. Analysis of these mice has found that they express the Cre recombinase and Cre reporters within Nkx2.1-expressing domains of the brain, thyroid, pituitary, and lung. Telencephalic expression of reporters begins at about embryonic day 10.5. Expression both of Cre and of recombination-based Cre reporters is weaker within the dorsalmost region of the MGE than in other Nkx2.1-expressing regions. In this paper, we present fate-mapping data on Nkx2.1-lineage neurons throughout the telencephalon, including the cerebral cortex, amygdala, olfactory bulb, striatum, globus pallidus, septum, and nucleus basalis.

Novel tricyclic imidazoline antagonists of the adenosine A1 receptor are described. For key compounds, the selectivity level over other adenosine receptor subtypes is examined along with their in vivo effects in a rat diuresis model. Compound 14, the (R)-isomer of 7,8-dihydro-8-ethyl-2-(4-bicyclo[2.2.2]octan-1-ol)-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one, is a particularly potent adenosine A1 receptor antagonist with good selectivity over the other three adenosine receptor subtypes: A1 (human) Ki=22 nM; A2A (human) Ki=4400 nM; A2B (human) Ki=580 nM; A3 (human) Ki>or=10,000 nM. Imidazoline 14 is a competitive adenosine A1 receptor antagonist with a pA2 value of 8.88 and is highly soluble in water (>100 mg/mL). In addition, it has an oral bioavailability of 84% and an oral half-life of 3.8 h in rats. When orally administered in a rat diuresis model, compound 14 promoted sodium excretion (ED50=0.01 mg/kg). This level of efficacy is comparable to that of BG9928, a selective adenosine A1 receptor antagonist that is currently in clinical trials as a treatment for congestive heart failure. Additional modifications to 14 also showed that the bridgehead hydroxyl group could be replaced with a propionic acid (compound 36) without a significant loss in binding affinity or in vivo activity.

Over the next 10 years, a generational group known as the Baby Boomers will become America's senior citizens and account for 22% of the country's population.Aging challenges such as sensory impairment may cause older adults to develop eating habits that may not align with developing medical conditions. This review addresses prevalence and severity of impairment for the five senses and the role of texture as human's age, such as the decline of olfactory acuity and the increase in basic taste thresholds. Despite the heterogenous impact of sensory impairment on older adults, it is not associated with reduced food liking. The food industry can implement strategies to help older adults overcome age-related sensory decline to make food choices that promote healthy aging. Food products should be evaluated holistically, from packaging to last bite, to better guide and encourage food purchase, consumption, and liking toward healthy aging among older adults. Practical ApplicationsUnderstanding the implications of age on the accuracy of senses helps the industry develop better strategies to encourage healthy food purchases and consumption toward healthy aging. Product development strategies should address both intrinsic and extrinsic attributes to overcome sensory impairment and to promote healthy nutrition and aging. | INTRODUCTIONGlobally, senior citizens are defined as adults over the age of 65. In the United States, this demographic is increasing as the generational group known as the Baby Boomers age. Baby Boomers are defined as adults born between 1946 and 1964(Merriam-Webster, 2021. Over the next 10 years, all Baby Boomers will be senior citizens. Americans over the age of 50 have a median net worth that is nearly twice as much as Americans between the age of 18 and 49 (Mintel, 2019a). This generational group accounts for 22% of the U.S. population whereas the millennial group accounts for 24% of the U.S. popu lation (Mintel, 2019b). Baby Boomers are largely overlooked despite their wealth and comparable size to millennial. Roughly 5% of U.S. advertising targets consumers over the age of 50 (Mintel, 2019a).Baby boomers should not be overlooked as this aging group has needs and wants that should be addressed to maintain a good quality of life and support healthy aging.There are several challenges that come with aging. The main concern for most is overall health and maintaining it. Though most boomers do not consider themselves "seniors" nor "dependent," it is common that they are experiencing the effects of aging or have seen the effects on their parents or peers. This could lead to fears of losing their independence and fears of being a burden. From a medical perspective, frailty and sarcopenia are two of many chronic conditions that impact seniors. Frailty is a multisystem disorder observed in the elderly, which includes the decline in mental and physical abilities (Clegg, Young, Iliffe, Rikkert, & Rockwood, 2013). Sarcopenia is the decline in skeletal muscle mass associated with aging, which contributes to frailty ...

Rationale Motivational deficits are a common symptom shared across multiple psychiatric and neurodegenerative disorders. Effort-based decision-making tasks are a translatable method for assessing motivational state. Much of the preclinical validation of the task derives from acute pharmacological manipulations in rats. However, mice currently offer a greater genetic toolkit to study risk genes and phenotypic models. Despite this, there is limited characterisation of their behaviour in this type of motivation task. Objectives Here, we investigate the effort for reward (EfR) task as a measure of motivational state in mice using drugs previously shown to modulate effort-based decision-making in rats and humans. Method Using male C57bl/6j mice, we test the effects of drugs which modulate DA transmission. We also test the effects of CP101-606 which does not act directly via DA modulation but has been shown to exert beneficial effects on motivational state. Finally, we test the sensitivity of the task to a chronic corticosterone (CORT) treatment. Results Amphetamine, methylphenidate, and CP101606 in mice increased high-effort responses for high-value reward, while administration of haloperidol decreased high-effort responses. Surprisingly, tetrabenazine had no effect at the doses tested. Chronic, low-dose CORT consumption did not alter task performance. Conclusion These data suggest that the EfR task is sensitive to acute dopaminergic modulation and NR2B selective antagonism in mice. However, it may lack sensitivity to non-acute phenotypic models. Further work is required to demonstrate the utility of the task in this context.