Multisensory Stimulation Reverses Memory Impairment in Adrβ3KO Male Mice

Abstract

Norepinephrine plays an important role in modulating memory through its beta-adrenergic receptors (Adrβ: β1, β2 and β3). Here, we hypothesized that multisensory stimulation would reverse memory impairment caused by the inactivation of Adrβ3 (Adrβ3KO) with consequent inhibition of sustained glial-mediated inflammation. To test this, 21- and 86-day-old Adrβ3KO mice were exposed to an 8-week multisensory stimulation (MS) protocol that comprised gustatory and olfactory stimuli of positive and negative valence; intellectual challenges to reach food; the use of hidden objects; and the presentation of food in ways that prompted foraging, which was followed by analysis of GFAP, Iba-1 and EAAT2 protein expression in the hippocampus (HC) and amygdala (AMY). The MS protocol reduced GFAP and Iba-1 expression in the HC of young mice but not in older mice. While this protocol restored memory impairment when applied to Adrβ3KO animals immediately after weaning, it had no effect when applied to adult animals. In fact, we observed that aging worsened the memory of Adrβ3KO mice. In the AMY of Adrβ3KO older mice, we observed an increase in GFAP and EAAT2 expression when compared to wild-type (WT) mice that MS was unable to reduce. These results suggest that a richer and more diverse environment helps to correct memory impairment when applied immediately after weaning in Adrβ3KO animals and indicates that the control of neuroinflammation mediates this response.

Understanding exogenous factors and biological mechanisms for cognitive frailty: a multidisciplinary scoping review

“…More recently, in a pro-inflammatory mouse model, multisensory stimulation reversed memory impairment (Ravache et al, 2023). Karoglu-Eravsar et al (2021) further showed that EE with sensory components prevented age-related decline in synaptic dynamics in zebrafish.…”

Neural Correlates and Molecular Mechanisms of Memory and Learning

“…Three articles used animal models to investigate the effects of different interventions on memory and learning [ 20 , 21 , 22 ]. These studies explored the roles of multisensory stimulation, glucocorticoid receptor antagonism, and recognition memory in modulating hippocampal neurogenesis, synaptic plasticity, and fear-related behaviors.…”

“…These studies explored the roles of multisensory stimulation, glucocorticoid receptor antagonism, and recognition memory in modulating hippocampal neurogenesis, synaptic plasticity, and fear-related behaviors. Ravache et al investigated the effects of multisensory stimulation on memory impairment in a mouse model of obesity [ 20 ]. The authors showed that multisensory stimulation reverses memory deficits induced by the lack of adrenergic beta-3 receptor, which is involved in thermogenesis and energy expenditure.…”

Emerging Translational Research in Neurological and Psychiatric Diseases: From In Vitro to In Vivo Models

“…Additionally, non-invasive brain stimulation techniques have become an integral aspect of clinical research in mental illnesses [13,14]. Methods such as transcranial magnetic stimulation and transcranial direct current stimulation have been employed in preclinical models to investigate their potential therapeutic alternatives [15,16]. These techniques offer a unique opportunity to modulate neural activity in specific brain regions, mimicking the neuromodulatory effects observed in human studies [17][18][19].…”