Memory impairment is associated with the loss of regular oestrous cycle and plasma oestradiol levels in an activity-based anorexia animal model

Abstract

Our results demonstrate that starvation reduces the E2 levels which are associated with memory deficits in ABA rats. These effects might explain reduced memory capacity in patients with AN as a consequence of E2 deficiency and the potentially limited effectiveness of psychotherapeutic interventions in the starved state. Future studies should examine whether E2 substitution could prevent cognitive deficits and aid in earlier readiness for therapy.

Establishment of a chronic activity-based anorexia rat model

“…Our group already used these two stages of our modified ABA model to analyse the neurobiological consequences of two different starvation stages in parallel. We showed lower oestradiol and leptin plasma levels and showed the impaired recognition memory in ABA versus control animals to be more pronounced following chronic starvation (Paulukat et al, 2016). Oestradiol reduction was directly correlated to memory impairment, compatible with (but not proving) a causal role of oestrogen for certain forms of learning in ABA animals.…”

“…In a study by Riddle et al, mice with caloric restriction but no running wheel access developed a reduction of the oestrous phases (no amenorrhoea), indicating that hyperactivity could stimulate the development of cycle absence (Riddle et al, 2013). Amenorrhoea was associated with oestrogen deficiency in the plasma of our modified ABA model, further underlining its effect on hormonal physiology (Paulukat et al, 2016).…”

“…Later, this model was called the ABA model (for a review see: Méquinion et al, 2015b). ABA mimics some of the core features of AN, including increased running activity, oestrous cycle disturbances and altered hormone production (Belmonte et al, 2016;Lee and Kinzig, 2017;Paré, 1977;Paulukat et al, 2016;Watanabe et al, 1992). The developing hyperactivity in ABA models can potentially be explained evolutionarily with a food seeking behaviour.…”

Activity-Based Anorexia Reduces Body Weight without Inducing a Separate Food Intake Microstructure or Activity Phenotype in Female Rats—Mediation via an Activation of Distinct Brain Nuclei

“…These alterations are likely to be involved in several changes observed: besides a reduction in food intake and body weight also an intestinal barrier dysfunction (Jésus et al, 2014), a disruption of neural development in the hippocampus (Chowdhury et al, 2014) and an impairment of memory function (Paulukat et al, 2016), increased anxiety (Kinzig and Hargrave, 2010) and the development of stress ulcers (Doerries et al, 1991), features also observed (Kline, 1979; Ghadirian et al, 1993; Swinbourne and Touyz, 2007; Huber et al, 2015; Kjaersdam Telleus et al, 2015) or suspected in patients with AN. Taken together, activity-based anorexia—despite the major limitation of being an animal model merely mimicking features of a disease—is likely a suited tool to study aspects of the pathogenesis of human AN.…”

Rolle des Mikrobioms und der Darm-Gehirn-Interaktion bei Anorexia nervosa

“…Das Gehirn von Patientinnen mit AN zeigt auch einen massiven Volumenverlust der grauen und weißen Substanz [59], verbunden mit neuropsychologischen Defiziten und negativer Krankheitsprognose [60]. Unsere Gruppe konnte in einem AN-Tiermodell zudem eine über 50 %ige Reduktion der Astrozytenanzahl [61], eine reduzierte Zellneogenese in der weißen und grauen Substanz sowie eine reduzierte Lernleistung zeigen [62]. Dies unterstreicht die Relevanz der Darm-Gehirn-Achse [16,64], während die Anzahl des methanproduzierenden Archaeons Methanobrevibacter smithii in 3 Studien [16,63,64] erhöht war.…”