Multisensory Stimulation Reverses Memory Impairment in Adrβ(3)KO Male Mice

Norepinephrine plays an important role in modulating memory through its beta-adrenergic receptors (Adrβ: β(1), β(2) and β(3)). Here, we hypothesized that multisensory stimulation would reverse memory impairment caused by the inactivation of Adrβ(3) (Adrβ(3)KO) with consequent inhibition of sustained glial-mediated inflammation. To test this, 21- and 86-day-old Adrβ(3)KO 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 Adrβ(3)KO animals immediately after weaning, it had no effect when applied to adult animals. In fact, we observed that aging worsened the memory of Adrβ(3)KO 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 Adrβ(3)KO animals and indicates that the control of neuroinflammation mediates this response.