Multisensory Stimulation Reverses Memory Impairment in Adrβ3KO Male Mice

Author:

Ravache Thaís T.1ORCID,Batistuzzo Alice1,Nunes Gabriela G.1,Gomez Thiago G. B.1,Lorena Fernanda B.12ORCID,Do Nascimento Bruna P. P.12,Bernardi Maria Martha3,Lima Eduarda R. R.4,Martins Daniel O.4ORCID,Campos Ana Carolina P.45,Pagano Rosana L.4ORCID,Ribeiro Miriam O.1ORCID

Affiliation:

1. Programa de Pós-Graduação em Distúrbios do Desenvolvimento, Centro de Ciências Biológicas e da Saúde Universidade Presbiteriana Mackenzie, São Paulo 01302-907, SP, Brazil

2. Departamento de Medicina Translacional, Universidade Federal de São Paulo 04023-062, SP, Brazil

3. Graduate Program in Environmental and Experimental Pathology, Paulista University, São Paulo 04026-002, SP, Brazil

4. Laboratory of Neuroscience, Hospital Sírio-Libanês, São Paulo 01308-050, SP, Brazil

5. Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada

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.

Funder

Sao Paulo Research Foundation

Coordination for the Improvement of Higher Education Personnel

Pró-Reitoria de Extensão

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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