Intermittent fasting uncovers and rescues cognitive phenotypes in PTEN neuronal haploinsufficient mice

Author(s)

Cabral-Costa, J. V. ^[1] ; Andreotti, D. Z. ^{[1, 2]} ; Mello, N. P. ^[1] ; Scavone, C. ^[2] ; Camandola, S. ^[3] ; Kawamoto, E. M. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Lab Mol & Funct Neurobiol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Lab Mol Neuropharmacol, Sao Paulo - Brazil

^[3] NIA, Lab Neurosci, NIH, Baltimore, MD 21224 - USA

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 8, JUN 5 2018.
• Web of Science Citations: 1

Abstract

Phosphatase and tensin homolog (PTEN) is an important protein with key modulatory functions in cell growth and survival. PTEN is crucial during embryogenesis and plays a key role in the central nervous system (CNS), where it directly modulates neuronal development and synaptic plasticity. Loss of PTEN signaling function is associated with cognitive deficits and synaptic plasticity impairment. Accordingly, Pten mutations have a strong link with autism spectrum disorder. In this study, neuronal Pten haploinsufficient male mice were subjected to a long-term environmental intervention - intermittent fasting (IF) - and then evaluated for alterations in exploratory, anxiety and learning and memory behaviors. Although no significant effects on spatial memory were observed, mutant mice showed impaired contextual fear memory in the passive avoidance test - an outcome that was effectively rescued by IF. In this study, we demonstrated that IF modulation, in addition to its rescue of the memory deficit, was also required to uncover behavioral phenotypes otherwise hidden in this neuronal Pten haploinsufficiency model. (AU)

• FAPESP's process: 13/20594-2 - Characterization of the PTEN signaling biochemical effects on mice hippocampi under intermittent diet
• Grantee: João Victor Cabral Costa
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 15/25491-2 - Evaluation of the effects of the Klotho protein on the neuronal morphological alteration characteristics of the lack of PTEN protein
• Grantee: Natalia Prudente de Mello
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 14/18689-8 - Evaluation of the PTEN signaling effects over neurogenesis and cognition of mice under a physical exercise regimen
• Grantee: João Victor Cabral Costa
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 16/22996-9 - Evaluation of physical exercise effects on cognition of neuronal-PTEN deleted animals
• Grantee: Elisa Mitiko Kawamoto Iwashe
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/21308-8 - Evaluation of PTEN compartmentalization on neurogenesis and synaptic plasticity influenced by environmental factors
• Grantee: Elisa Mitiko Kawamoto Iwashe
• Support Opportunities: Research Grants - Young Investigators Grants