Long-Term Social Isolation Reduces Expression of the BDNF Precursor and Prolyl Endopeptidase in the Rat Brain

Abstract

Early-life stress is a risk factor for the development of behavioral and cognitive disorders in humans and animals. Such stressful situations include social isolation in early postnatal ontogenesis. Behavioral and cognitive impairments associated with neuroplastic changes in brain structures. We have found that after ten weeks of social isolation, male Wistar rats show behavioral abnormalities and cognitive deficit, accompanied by an increase in the relative expression of gene encoding serine protease prolyl endopeptidase (PREP, EC 3.4.21.26) in the brain frontal cortex. The present study aimed to assess synaptophysin (SYP), brain-derived neurotrophic factor precursor (proBDNF), and PREP expression using Western blot in the brain structures – the hippocampus, frontal cortex, and striatum of the rats subjected to prolonged social isolation compared with group-housed animals. Twenty Wistar rats were used for this study (10 males and 10 females). Experimental animals (5 males and 5 females) were kept one per cage for nine months, starting from the age of one month. Ten-month-old socially isolated rats showed memory deficit in passive avoidance paradigm and Morris Water Maze and reactivity to novelty reduction. We used monoclonal antibodies for the Western blot analysis of the expression of SYP, proBDNF, and PREP in the rat brain structures. Social isolation caused a proBDNF expression reduction in the frontal cortex in females and a reduction in PREP expression in the striatum in males. These data suppose that neurotrophic factors and PREP are involved in the mechanisms of behavioral and cognitive impairments observed in the rats subjected to prolonged social isolation with an early life onset.

Chronic haloperidol administration downregulates select BDNF transcript and protein levels in the dorsolateral prefrontal cortex of rhesus monkeys

“…Reported changes in BDNF expression are confounded by reduced environmental stimulation and social interactions experienced by the rhesus monkeys. Several studies have demonstrated stress-induced alterations in BDNF expression in various brain regions in rodents (111)(112)(113)(114)(115)(116). Moreover, BDNF mRNA and protein levels in several brain areas are increased following environmental enrichment (117)(118)(119).…”

Mediation Analyses of the Role of Apathy on Motoric Cognitive Outcomes

“…This should generate deeper exploration into the inflammatory pathways but also promote investigation of additional important biomarkers associated with motor and cognitive function. Additionally, we plan to investigate how apathy may promote behaviors such as social isolation and decreased motor activity, which may promote inflammatory cytokines [ 59 , 60 , 61 , 62 , 63 , 64 ] and decrease brain-derived neurotrophic factor [ 65 , 66 , 67 , 68 , 69 ]. Another mechanism that warrants further exploration is the relationship between blood–brain barrier (BBB) disruption, which can occur in normal aging, and disease states including cerebrovascular disease and metabolic syndrome [ 70 , 71 , 72 ].…”