Neonatal loss of FGFR2 in astroglial cells affects locomotion, sociability, working memory, and glia-neuron interactions in mice.

Fibroblast growth factor receptor 2 (FGFR2) is almost exclusively expressed in glial cells in postnatal mouse brain, but its impact in glia for brain behavioral functioning is poorly understood. We compared behavioral effects from FGFR2 loss in both neurons and astroglial cells and from FGFR2 loss in astroglial cells by using either the pluripotent progenitor-driven hGFAP-cre or the tamoxifen-inducible astrocyte-driven GFAP-creERT2 in Fgfr2 floxed mice. When FGFR2 was eliminated in embryonic pluripotent precursors or in early postnatal astroglia, mice were hyperactive, and had small changes in working memory, sociability, and anxiety-like behavior. In contrast, FGFR2 loss in astrocytes starting at 8 weeks of age resulted only in reduced anxiety-like behavior. Therefore, early postnatal loss of FGFR2 in astroglia is critical for broad behavioral dysregulation. Neurobiological assessments demonstrated that astrocyte-neuron membrane contact was reduced and glial glutamine synthetase expression increased only by early postnatal FGFR2 loss. We conclude that altered astroglial cell function dependent on FGFR2 in the early postnatal period may result in impaired synaptic development and behavioral regulation, modeling childhood behavioral deficits like attention deficit hyperactivity disorder (ADHD).

Adolescent female rats prone to the activity based anorexia (ABA) paradigm have altered hedonic responses and cortical astrocyte density compared to resistant animals.

OBJECTIVE: Anhedonia, which in part involves the lack of pleasure in consuming palatable food, is a long-lasting symptom observed in patients both when acutely ill and when long term recovered from Anorexia Nervosa. The neurocircuitry underlying this phenomenon is not well understood. Here we use the preclinical activity-based anorexia (ABA) model in adolescent female rats to assess the impact of excessive exercise, limited food intake and acute weight loss, on adolescent female rat orofacial responding to intraoral sucrose, as measured by the taste reactivity test (TRT). Animals were identified as either prone or resistant to this paradigm based on a weight loss criterion. Measures of food intake, running wheel activity, taste reactivity and medial prefrontal cortex astrocyte expression were compared across groups. METHODS: Adolescent female rats implanted with an intraoral catheter were given a TRT using 1 M (M) sucrose at baseline, max weight loss (25% weight loss from start of ABA or 7 full days on the paradigm) or 10 days recovered from the ABA paradigm. Animals were sacrificed after the final TRT and astrocyte density was measured via immunohistochemistry. RESULTS: Animals resistant to the ABA paradigm ran less than prone animals during the ABA period. Additionally, we found that resistant animals displayed more cumulative 'liking' responses to sucrose compared to prone animals at maximum weight loss. Finally, we found prone animals 10-days recovered from ABA had reduced medial prefrontal cortex astrocyte density compared to levels in resistant animals. DISCUSSION: Rats presented with the physiological challenge of the ABA paradigm either adapt their behavior to stabilize their body weight (i.e. resistant), or rapidly lose weight (i.e. prone). Furthermore, we found that prone animals have reduced orofacial responding to 1 M sucrose at maximum weight loss compared to responses in resistant animals, and this anhedonia-like behavior may be a result of reduced astrocyte density that affects cortical function.

Gastrointestinal symptomatology, diagnosis, and treatment history in patients with underweight avoidant/restrictive food intake disorder and anorexia nervosa: Impact on weight restoration in a meal-based behavioral treatment program.

OBJECTIVE: Gastrointestinal (GI) concerns are often presumed to complicate nutritional rehabilitation for restrictive eating disorders, yet their relationship to weight restoration outcomes is unclear. This retrospective chart review examined GI history and weight-related discharge outcomes in primarily adult, underweight inpatients with anorexia nervosa (AN, N = 107) or avoidant/restrictive food intake disorder (ARFID, N = 22) treated in a meal-based, behavioral eating disorder program. METHOD: Lifetime GI symptomatology, diagnoses, diagnostic tests, and procedures were abstracted from medical records. Generalized linear models examined associations of GI diagnoses, tests, and procedures with discharge BMI and rate of weight gain. RESULTS: Ninety-nine percent of patients reported GI symptomatology and 83% had one or more GI diagnoses; with constipation and GERD most common. GI diagnoses (p <.01) and testing (p <.001) were more common in ARFID than AN. Average inpatient weight gain (1.59 kg/week), and discharge BMI (18.5 kg/m2 ), did not differ by group. Slower weight gain in patients with (1.3 kg/week), versus without (1.7 kg/week), history of tube feeding (p = .02), accounted for a main effect of GI procedures on inpatient rate of gain (p = .01). DISCUSSION: Despite ubiquitous GI symptomatology, meal-based weight restoration achieved average weekly weight gain above recommended APA guidelines for hospitalized patients with an eating disorder. History of tube feeding was associated with slower mean weight gain, which remained, however, within recommended APA guidelines.

AMPK agonist AICAR improves cognition and motor coordination in young and aged mice.

Normal aging can result in a decline of memory and muscle function. Exercise may prevent or delay these changes. However, aging-associated frailty can preclude physical activity. In young sedentary animals, pharmacological activation of AMP-activated protein kinase (AMPK), a transcriptional regulator important for muscle physiology, enhanced spatial memory function, and endurance. In the present study we investigated effects of AMPK agonist 5-aminoimidazole-4-carboxamide riboside (AICAR) on memory and motor function in young (5- to 7-wk-old) and aged (23-mo-old) female C57Bl/6 mice, and in young (4- to 6-wk-old) transgenic mice with muscle-specific mutated AMPK α2-subunit (AMPK-DN). Mice were injected with AICAR (500 mg/kg) for 3-14 d. Two weeks thereafter animals were tested in the Morris water maze, rotarod, and open field. Improved water maze performance and motor function were observed, albeit at longer duration of administration, in aged (14-d AICAR) than in young (3-d AICAR) mice. In the AMPK-DN mice, the compound did not enhance behavior, providing support for a muscle-mediated mechanism. In addition, microarray analysis of muscle and hippocampal tissue derived from aged mice treated with AICAR revealed changes in gene expression in both tissues, which correlated with behavioral effects in a dose-dependent manner. Pronounced up-regulation of mitochondrial genes in muscle was observed. In the hippocampus, genes relevant to neuronal development and plasticity were enriched. Altogether, endurance-related factors may mediate both muscle and brain health in aging, and could play a role in new therapeutic interventions.