5 research outputs found
Early neuromodulation prevents the development of brain and behavioral abnormalities in a rodent model of schizophrenia
The notion that schizophrenia is a neurodevelopmental disorder in which neuropathologies evolve gradually over the
developmental course indicates a potential therapeutic window during which pathophysiological processes may be modified to
halt disease progression or reduce its severity. Here we used a neurodevelopmental maternal immune stimulation (MIS) rat model
of schizophrenia to test whether early targeted modulatory intervention would affect schizophrenia’s neurodevelopmental course.
We applied deep brain stimulation (DBS) or sham stimulation to the medial prefrontal cortex (mPFC) of adolescent MIS rats and
respective controls, and investigated its behavioral, biochemical, brain-structural and -metabolic effects in adulthood. We found
that mPFC-DBS successfully prevented the emergence of deficits in sensorimotor gating, attentional selectivity and executive
function in adulthood, as well as the enlargement of lateral ventricle volumes and mal-development of dopaminergic and
serotonergic transmission. These data suggest that the mPFC may be a valuable target for effective preventive treatments. This may
have significant translational value, suggesting that targeting the mPFC before the onset of psychosis via less invasive
neuromodulation approaches may be a viable preventive strategy.We thank Renate Winter, Doris Zschaber and Roselies Pickert for excellent technical
assistance. This research was conducted under the EraNet Neuron framework
(DBS_F20rat) and supported by the BMBF, Germany (B01EW1103, 01EE1403A),
Fundación Mapfre, Comunidad de Madrid and the Ministry of Economy and
Competitiveness ISCIII-FIS grants (PI14/00860, CPII/00005) co-financed by ERDF (FEDER) Funds from the European Commission, ‘A way of making Europe’, Spain (PI14/00860, CPII/00005, MV1500002), the CSO-MOH, Israel (3-8580) and the Canadian
Institutes of Health Research, Canada (CIHR, 110068), and co-financed by the DFG,
Germany (WI 2140/1-1/2; WI 2140/2-1).Publicad
Food-seeking behavior is triggered by skin ultraviolet exposure in males.
Sexual dimorphisms are responsible for profound metabolic differences in health and behavior. Whether males and females react differently to environmental cues, such as solar ultraviolet (UV) exposure, is unknown. Here we show that solar exposure induces food-seeking behavior, food intake, and food-seeking behavior and food intake in men, but not in women, through epidemiological evidence of approximately 3,000 individuals throughout the year. In mice, UVB exposure leads to increased food-seeking behavior, food intake and weight gain, with a sexual dimorphism towards males. In both mice and human males, increased appetite is correlated with elevated levels of circulating ghrelin. Specifically, UVB irradiation leads to p53 transcriptional activation of ghrelin in skin adipocytes, while a conditional p53-knockout in mice abolishes UVB-induced ghrelin expression and food-seeking behavior. In females, estrogen interferes with the p53-chromatin interaction on the ghrelin promoter, thus blocking ghrelin and food-seeking behavior in response to UVB exposure. These results identify the skin as a major mediator of energy homeostasis and may lead to therapeutic opportunities for sex-based treatments of endocrine-related diseases