Multisensory Stimulation Reverses Memory Impairment in Adr & beta;3KO Male Mice

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Ravache, Thais T. ; Batistuzzo, Alice ; Nunes, Gabriela G. ; Gomez, Thiago G. B. ; Lorena, Fernanda B. ; Do Nascimento, Bruna P. P. ; Bernardi, Maria Martha ; Lima, Eduarda R. R. ; Martins, Daniel O. ; Campos, Ana Carolina P. ; Pagano, Rosana L. ; Ribeiro, Miriam O.

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 24, n. 13, p. 17-pg., 2023-07-01.

Abstract

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

• FAPESP's process: 19/13781-7 - Translational analysis of the therapeutic mechanisms of deep brain stimulation in Parkinson's Disease
• Grantee: Rosana de Lima Pagano
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/18277-0 - Thr92Ala-D2 polimorphism and behavior
• Grantee: Miriam Oliveira Ribeiro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/04491-0 - Effect of the thyroid hormone receptor beta (TRbeta)-selective thyromimetic GC-1 on brain of 3xTg-AD mice
• Grantee: Bruna Pascarelli Pedrico Do Nascimento
• Support Opportunities: Scholarships in Brazil - Doctorate