Impact of High-Fat Diet and Early Stress on Depressive-Like Behavior and Hippocampal Plasticity in Adult Male Rats

Abstract

During development, the brain goes through fundamental processes, including organization of neural networks and plasticity. Environmental interventions may change initial brain programming, leading to long-lasting effects and altering the susceptibility to psychopathologies, including depression disorder. It is known that depression is a psychiatric disorder with a high prevalence worldwide, including high rates among adolescents. In this study, we evaluated whether social isolation in the prepubertal period and chronic use of high-fat diet (HFD) may induce depressive-like behavior in male adult rats. We also investigated hippocampal plasticity markers and neurotransmitter systems. We found both social isolation and HFD induced a depressive-like behavior in the forced swimming task. Moreover, chronic HFD reduced synaptic markers in hippocampus, demonstrated by reductions in βIII-tubulin (neuronal marker), PSD-95, SNAP-25, and neurotrophin-3. The HFD group also presented decreased glutamatergic and GABAergic receptors subunits. On the other hand, stress affected hippocampal brain-derived neurotrophic factor (BDNF) signaling pathways, and increased expression of subunit of the NMDA receptor (NR2A). Both factors (stress and diet) decreased GR in the hippocampus without affecting plasma corticosterone at basal levels. Interactions between early stress and HFD access were observed only in the BNDF receptor (tropomyosin receptor kinase B; TrkB) and synaptophysin. In summary, these findings showed that a brief social isolation and chronic HFD, during a sensitive developmental period, cause depressive-like behavior in adulthood. The mechanisms underlying these behavioral effects may involve changes in the levels of synaptic proteins in hippocampus: HFD consumption appears to affect synaptic markers, while social isolation affected BDNF signaling more significantly.

Inhibiting RIP1 Improves Chronic Stress-Induced Cognitive Impairments in D-Galactose-Induced Aging Mice

“…NMDA receptor subunits (NR1, NR2A, and NR2B) and AMPA receptor subunits (GluA1 and GluA2) are closely involved in brain function, and are also important targets of chronic stress ( Costa-Nunes et al, 2014 ; Pacheco et al, 2017 ; Shang et al, 2017 ; Arcego et al, 2018 ). The effects of chronic stress on NMDA and AMPA receptors vary based on the type of stress.…”

“…For example, Pacheco et al (2017) found that restraint stress (2.5 h/day) for 14 days triggered an increase in NR1 protein level in the dorsal hippocampus. Arcego et al (2018) found that social isolation stress increased the expression of subunit NR2A of the NMDA receptor. In contrast, Costa-Nunes et al (2014) found that social defeat and predation stress increased NR2A mRNA expression, but not the expression of NR2B and NR1 mRNA in the hippocampus of mice.…”

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“…Social isolation/ deprivation of rats and mice induces chronic stress and may be applied usefully as a laboratory animal model for neuropsychiatric disorders, such as schizophrenia spectrum disorders and clinical depression. 30,31 The decreased expression of BDNF has been observed generally as a consequence of these conditions with the downregulation of BDNF seemingly associated with increased anxiety-like symptoms/ behaviors among these rodents. 32 In patients presenting newlydiagnosed multiple schlerosis, the observed cognitive dysfunction was most especially noticeable in male patients concomitant with reduced concentrations of BDNF in plasma.…”

Social interaction and network structure in groups ofDrosophilamales are shaped by prior social experience and group composition

“…Additionally, studies from various animal species 21,22,[73][74][75] including Drosophila have shown that isolation results in increased activity/arousal, increased aggression and in some cases social avoidance. Extending these findings to group context, we predicted groups of solitary flies to exhibit increased activity, increased aggression and reduced social interaction.…”