Multisensory Stimulation Improves Cognition and Behavior in Adult Male Rats Born to LT4-treated Thyroidectomized Dams

Author:

Batistuzzo Alice1ORCID,de Almeida Guilherme G1ORCID,Brás Tayna S1ORCID,Zucato Victoria P1ORCID,Arnold Alexandre J T1ORCID,Giannocco Gisele2ORCID,Sato Juliana M3ORCID,Yamanouchi Laís M1ORCID,Dias Eduardo1ORCID,Lorena Fernanda B3ORCID,do Nascimento Bruna P P3,Bianco Antonio C4ORCID,Ribeiro Miriam O1ORCID

Affiliation:

1. Developmental Disorders Program, Center for Biological Sciences and Health, Mackenzie Presbyterian University , Sao Paulo SP 01302-907 , Brazil

2. Departamento de Medicina, Laboratório de Endocrinologia e Medicina Translacional, Universidade Federal de São Paulo, UNIFESP/EPM, e Departamento de Ciências Biológicas, Universidade Federal de São Paulo, UNIFESP , Diadema, SP 09972-270 , Brazil

3. Postgraduate Program in Translational Medicine, Department of Medicine, Paulista School of Medicine, Federal University of Sao Paulo , Sao Paulo, SP 04021-001 , Brazil

4. Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, University of Chicago , Chicago, IL 60637 , USA

Abstract

Abstract Gestational hypothyroidism can impair development, cognition, and mood. Here, we tested whether multisensory stimulation (MS) improves the phenotype of rats born to surgically thyroidectomized (Tx) dams suboptimally treated with LT4. 8-week-old female Tx Wistar rats were kept on daily LT4 (0.7 µg/100 g body weight) dosed by gavage (serum TSH and T4 levels indicated moderate hypothyroidism) and 3 weeks later placed for breeding. MS of the litter started at age 60 days and lasted for 8 weeks. It consisted of twice per week of physical, cognitive, sensorial, and food stimuli. The offspring were assessed before and after MS for standardized tests of locomotor activity, cognition, and mood. Gestational hypothyroidism resulted in reduced litter size and increased offspring mortality. The pups exhibited delayed physical development, impairment of short- and long-term memory, and anxiety- and depressive-like behaviors. Nonetheless, ambulatory activity, social memory, and social preference were not affected by gestational hypothyroidism. MS restored short-term memory and anxiety while improving depressive like-behaviors. MS did not improve long-term memory. MS also did not modify the performance of control litter born to intact dams. We conclude that cognition and mood impairments caused by moderate gestational hypothyroidism were reversed or minimized in rats through MS. Further studies should define the molecular mechanisms involved.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo

Pró-Reitoria de Extensão

Coordenação De Aperfeiçoamento De Pessoal De Nível Superior

National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

The Endocrine Society

Subject

Endocrinology

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