[Effects of fasting on anxiety-and depression-like behaviors in mice and the role of the paraventricular thalamus in the underlying mechanism].

Objective: To investigate the effects of fasting on anxiety-and depression-like behaviors in mice, and to elucidate the underlying neural mechanisms. Methods: Eight-week-old male C57BL/6J mice (n=44) and Fos-2A-iCreER transgenic mice (n=48) were randomly assigned using a random number table.The male C57BL/6J mice were divided into six groups (n=36): anxiety-like models were established by 2-hour acute restraint stress (ARS), depression-like models were induced by intraperitoneal injection of lipopolysaccharide, and control groups were also set up. Within each model, mice were further divided into a fasting group (24-hour food deprivation) and an ad libitum feeding group. Fasting efficacy was assessed by monitoring changes in body weight and food intake. Anxiety-like behaviors were evaluated using the open field test and elevated plus maze test, while depression-like behaviors were assessed using the tail suspension test and forced swimming test. Whole-brain neuronal activation in response to fasting was detected in both fasted and non-fasted C57BL/6J mice (n=8) was detected through c-Fos immunofluorescence staining. Subsequently, the Fos-2A-iCreER transgenic mice were selected. The targeted recombination into active promoters (TRAP) technique was employed to specifically label fasting-activated neurons, and chemogenetic techniques were employed to activate or inhibit fasting-related neuronal ensembles (n=24 per experiment). Anxiety-like and depression-like models were re-established separately, and mice in each model were divided into a fasting group (24-hour food deprivation) and an ad libitum feeding group, in order to investigate the effects of activating or inhibiting neurons related to fasting on anxiety-and depression-like behaviors. Results: The open field test and the elevated plus maze test provided evidence that anxiety-like models had been successfully established. In addition, the tail suspension test and the forced swimming test provided evidence that depression models had been successfully established. In comparison with the ad libitum feeding group, the mice fasted for 24 h showed lower body weight and higher food intake (all P<0.05). Fasted mice demonstrated increased distance travelled, prolonged duration, and elevated entries in the central area of the open field, as well as greater distance traveled, higher percentage of duration, and more entries in the open arms of the elevated plus maze. Additionally, fasted mice showed shorter immobility times in both the tail suspension test and the forced swimming test. All differences were statistically significant (all P<0.05). c-Fos staining revealed enhanced neuronal activation in the paraventricular thalamus (PVT) region after fasting (all P<0.05). Chemogenetic activation of fasting-related neuronal ensembles in the PVT mimicked the anti-anxiety and anti-depression effects observed following fasting: anxious mice showed greater distance traveled, longer duration, and more entries in the central area of the open field, as well as greater distance traveled, higher percentage of duration, and more entries in the open arms of the elevated plus maze; depressed mice showed shorter immobility times in both the tail suspension test and the forced swim test (all P<0.05).Conversely, chemogenetic inhibition of these neuronal ensembles reversed these effects (all P<0.05). Conclusion: Fasting activates PVT-related neuronal ensembles to elicit anti-anxiety and antidepression effects in mice.