Neonatal Handling Positively Modulates Anxiety, Sensorimotor Gating, Working Memory, and Cortico-Hippocampal Neuroplastic Adaptations in Two Genetically Selected Rat Strains Differing in Emotional and Cognitive Traits
Río-Álamos, Cristóbal (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Serra, Maria Pina (University of Cagliari)
Sanna, Francesco (University of Cagliari)
Piludu, Maria A. (University of Cagliari)
Boi, Marianna (University of Cagliari)
Cañete, Toni (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Sampedro-Viana, Daniel (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Oliveras, Ignasi (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Tobeña, Adolf 1950- (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Corda, Maria G. (University of Cagliari)
Giorgi, Osvaldo (University of Cagliari)
Fernández-Teruel, Alberto (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Quartu, Marina (University of Cagliari)

Data:	2025
Resum:	Background/Objectives: The bidirectional selection of the Roman low- (RLA) and Roman high-avoidance (RHA) rat strains for extremely slow vs. very rapid acquisition of the two-way (shuttle-box) avoidance response has generated two divergent phenotypic profiles: RHA rats exhibit a behavioural pattern and gene expression profile in the frontal cortex and hippocampus (HPC) that are relevant to social and attentional/cognitive schizophrenia-linked symptoms; on the other hand, RLA rats display phenotypic traits linked to increased anxiety and sensitivity to stress-induced depression-like behaviours. The present studies aimed to evaluate the enduring and potentially positive effects of neonatal handling-stimulation (NH) on the traits differentiating these two strains of rats. Methods: We evaluated the effects of NH on anxious behaviour, prepulse inhibition of startle (PPI), spatial working memory, and hormone responses to stress in adult rats of both strains. Furthermore, given the proposed involvement of neuronal/synaptic plasticity and neurotrophic factors in the development of anxiety, stress, depression, and schizophrenia-related symptoms, using Western blot (WB) we assessed the effects of NH on the content of brain-derived neurotrophic factor (BDNF), its trkB receptor and Polysialilated-Neural Cell Adhesion Molecule (PSA-NCAM), in the prefrontal cortex (PFC), anterior cingulate cortex (ACg), ventral (vHPC), and dorsal (dHPC) hippocampus of adult rats from both strains. Results: NH increased novelty-induced exploration and reduced anxiety, particularly in RLA rats, attenuated the stress-induced increment in corticosterone and prolactin plasma levels, and improved PPI and spatial working memory in RHA rats. These effects correlated to long-lasting increases of BDNF and PSA-NCAM content in PFC, ACg, and vHPC. Conclusions: Collectively, these findings show enduring and distinct NH effects on neuroendocrine and behavioural and cognitive processes in both rat strains, which may be linked to neuroplastic and synaptic changes in the frontal cortex and/or hippocampus.
Ajuts:	Agencia Estatal de Investigación PID2023-147693NB-I00 Agencia Estatal de Investigación PID2020-114697GB-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca ICREA-Academia-2023 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00557
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Anxiety ; Stress ; Prepulse inhibition ; Spatial working memory ; Roman highand low-avoidance rats ; Neonatal handling ; BDNF ; TrkB ; PSA-NCAM ; Prefrontal cortex ; Hippocampus
Publicat a:	Brain sciences, Vol. 15 Núm. 8 (august 2025) , p. 776, ISSN 2076-3425

DOI: 10.3390/brainsci15080776
PMID: 40867109

24 p, 1.4 MB

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