Early-life and chronic exposure to high-fat diet alters noradrenergic and glutamatergic neurotransmission in the male rat amygdala and hippocampus under cognitive challenges.

Childhood obesity increases the risk of health and cognitive disorders in adulthood. Consuming high-fat diets (HFD) during critical neurodevelopmental periods, like childhood, impairs cognition and memory in humans and animals, affecting the function and connectivity of brain structures related to emotional memory. However, the underlying mechanisms of such phenomena need to be better understood. This study aimed to investigate the neurochemical profile of the amygdala and hippocampus, brain structures involved in emotional memory, during the acquisition of conditioned odor aversion in male rats that consumed a HFD from weaning to adulthood. The rats gained weight, experienced metabolic changes, and reduced insulin sensitivity and glucose tolerance. Rats showed enhanced odor aversion memory, contrary to the expected cognitive impairments. This memory enhancement was accompanied by increased noradrenergic and glutamatergic neurotransmission in the amygdala and hippocampus. Importantly, this upregulation was specific to stimuli exposure, as basal neurotransmitter levels remained unaltered by the HFD. Our results suggest that HFD modifies cognitive function by altering neurochemical signaling, in this case, upregulating neurotransmitter levels rendering a stronger memory trace, demonstrating that metabolic dysfunctions do not only trigger exclusively detrimental plasticity processes but also render enhanced plastic effects depending on the type of information.

Understanding Sociodemographic Factors among Hispanics Through a Population-Based Study on Testicular Cancer in Mexico.

Testicular cancer (TCa) is a rare malignancy affecting young men worldwide. Sociodemographic factors, especially socioeconomic level (SEL) and healthcare access, seem to impact TCa incidence and outcomes, particularly among Hispanic populations. However, limited research has explored these variables in Hispanic groups. This study aimed to investigate sociodemographic and clinical factors in Mexico and their role in health disparities among Hispanic TCa patients. We retrospectively analyzed 244 Mexican TCa cases between 2007 and 2020 of a representative cohort with diverse social backgrounds from a national reference cancer center. Logistic regression identified risk factors for fatality: non-seminoma histology, advanced stage, and lower education levels. Age showed a significant trend as a risk factor. Patient delay and healthcare distance lacked significant associations. Inadequate treatment response and chemotherapy resistance were more likely in advanced stages, while higher education positively impacted treatment response. Cox regression highlighted non-seminoma histology, below-median SEL, higher education, and advanced-stage survival rates. Survival disparities emerged based on tumor histology and patient SEL. This research underscores the importance of comprehensive approaches that integrate sociodemographic, biological, and environmental factors to address health disparities improving outcomes through personalized interventions in Hispanic individuals with TCa.

Voluntary physical activity improves spatial and recognition memory deficits induced by post-weaning chronic exposure to a high-fat diet.

Childhood and adolescent exposure to obesogenic environments has contributed to the development of several health disorders, including neurocognitive impairment. Adolescence is a critical neurodevelopmental window highly influenced by environmental factors that affect brain function until adulthood. Post-weaning chronic exposure to a high-fat diet (HFD) adversely affects memory performance; physical activity is one approach to coping with these dysfunctions. Previous studies indicate that voluntary exercise prevents HFD's detrimental effects on memory; however, it remains to evaluate whether it has a remedial/therapeutical effect when introduced after a long-term HFD exposure. This study was conducted on a diet-induced obesity mice model over six months. After three months of HFD exposure (without interrupting the diet) access to voluntary physical activity was provided. HFD produced weight gain, increased adiposity, and impaired glucose tolerance. Voluntary physical exercise ameliorated glucose tolerance and halted weight gain and fat accumulation. Additionally, physical activity mitigated HFD-induced spatial and recognition memory impairments. Our data indicate that voluntary physical exercise starting after several months of periadolescent HFD exposure reverses metabolic and cognitive alterations demonstrating that voluntary exercise, in addition to its known preventive effect, also has a restorative impact on metabolism and cognition dysfunctions associated with obesity.

Susceptibility to GSK3ß-induced tau phosphorylation differs between the young and aged hippocampus after Wnt signaling inhibition.

The abnormal phosphorylation of the microtubule-associated protein tau is a prominent aspect of Alzheimer's disease (AD). Considerable evidence suggests that glycogen synthase kinase 3ß (GSK3ß) and the protein phosphatase 2A (PP2A) are involved in normal and pathological tau phosphorylation. However, the mechanisms underlying a shift of the phosphorylation/dephosphorylation balance that leads to abnormal tau phosphorylation remains unknown. The canonical Wnt pathway negatively regulates GSK3ß activity, and this signaling pathway has also been found to be dysregulated in the AD brain. Here, we report that the Wnt antagonist Dkk-1 selectively increases tau phosphorylation in the hippocampus of aged rats at Ser199/202, Ser396/404, and Ser214 sites. In the aged hippocampus, the inhibition of Wnt signaling is also accompanied by reduced PP2A activity. This study suggests that aging promotes tau hyperphosphorylation after Wnt inhibition, due to an imbalance between GSK3ß and PP2A activities.

GSK3 Function in the Brain during Development, Neuronal Plasticity, and Neurodegeneration.

GSK3 has diverse functions, including an important role in brain pathology. In this paper, we address the primary functions of GSK3 in development and neuroplasticity, which appear to be interrelated and to mediate age-associated neurological diseases. Specifically, GSK3 plays a pivotal role in controlling neuronal progenitor proliferation and establishment of neuronal polarity during development, and the upstream and downstream signals modulating neuronal GSK3 function affect cytoskeletal reorganization and neuroplasticity throughout the lifespan. Modulation of GSK3 in brain areas subserving cognitive function has become a major focus for treating neuropsychiatric and neurodegenerative diseases. As a crucial node that mediates a variety of neuronal processes, GSK3 is proposed to be a therapeutic target for restoration of synaptic functioning and cognition, particularly in Alzheimer's disease.