Pandolfo, P. | bioRxiv Science

bioRxiv2023

Effects of sex and gestational exercise on pain perception, BDNF and irisin levels in an animal model of ADHD

Abnormal cognitive and sensorial properties have been reported in patients with psychiatric and neurodevelopmental conditions, such as attention deficit hyperactivity disorder (ADHD). ADHD patients exhibit impaired dopaminergic signaling and plasticity in brain areas related to cognitive and sensory processing. The spontaneous hypertensive rat (SHR), in comparison to the Wistar Kyoto rat (WKY), is the most used genetic animal model to study ADHD. Brain neurotrophic factor (BDNF), critical for midbrain and hippocampal dopaminergic neuron survival and differentiation, is reduced in both ADHD subjects and SHR. Physical exercise (e.g. swimming) promotes neuroplasticity and improves cognition by increasing BDNF and irisin. Here we investigate the effects of gestational swimming on sensorial and behavioral phenotypes, striatal dopaminergic parameters, and hippocampal FNDC5/irisin and BDNF levels observed in WKY and SHR. Gestational swimming improved nociceptive reflex impairment in SHR rats and increased hippocampal BDNF levels in a sex-dependent manner in adolescent offspring. Sex differences were observed in hippocampal FNDC5/irisin levels, with females presenting lower levels than males. Our results contribute to the notion that swimming during pregnancy is a promising alternative to improve ADHD phenotypes in the offspring. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/551984v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@1737c93org.highwire.dtl.DTLVardef@f7bb8aorg.highwire.dtl.DTLVardef@3999f0org.highwire.dtl.DTLVardef@1a981a2_HPS_FORMAT_FIGEXP M_FIG C_FIG

animal behavior and cognition↗

bioRxiv2023

Gestational physical exercise prevents early-life behavioral impairments and normalizes dopamine D2 receptor expression in the frontal cortex in the offspring of a rat model of attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is characterized by inattention, hyperactivity and impulsivity, and develops most frequently during childhood and adolescence. Spontaneously hypertensive rats (SHR) are the most used experimental model for the study of ADHD. SHR exhibit behavioral impairments that recapitulate phenotypes observed in individuals with ADHD. SHR further develop dopaminergic hypofunction in frontostriatal circuits and an imbalance in dopamine and norepinephrine systems. Maternal physical exercise (e.g., swimming) during pregnancy has been shown to promote angiogenesis, neurogenesis, learning, and memory in the offspring of control rats. We investigated the impact of gestational swimming on behavioral and dopaminergic parameters in childhood (1-2 weeks of age) and adolescent (4-5 weeks of age) SHR and Wistar Kyoto rats (WKY), used as a control. Maternal gestational swimming resulted in a reversal of neurodevelopmental impairments in behavior, assessed by the righting reflex and olfactory recognition tests, in the offspring. Furthermore, during adolescence, SHRs from exercised dams exhibited reduced novelty seeking, an important behavioral trait in this developmental period. Finally, SHRs exhibited increased expression of dopamine transporter (DAT) and D2 receptors (D2R) in the frontal cortex. D2R expression was normalized in the frontal cortex of adolescent SHRs whose mothers were exercised. Results suggest that physical exercise during pregnancy could be an effective preventative strategy against ADHD-associated behavioral and neurochemical phenotypes in the offspring. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/550350v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@1a3ca8corg.highwire.dtl.DTLVardef@46d319org.highwire.dtl.DTLVardef@1cd1eddorg.highwire.dtl.DTLVardef@1a54431_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗